Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.68128841
PAI 1 was 3 4 fold enhanced as compared with uncomplexed uPAR bound uPA . 0.68128841^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.5583375
This PAI 1 formed 1 : 1 complexes with uPA and also with the single and two chain forms of tPA . 0.5583375^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :1.1869255
Receptor bound active uPA can also interact with its specific type 1 inhibiror ( PAI 1 ) which is therefore able to inhibit the cell surface plasmin formation . 1.1869255^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.94458769
These constants although lower than those for uPA in solution still represent rather rapid inhibition of the enzyme , and demonstrate that uPA bound to its specific cellular receptor remains available for efficient inhibition by PAI ' s , which may therefore play a major role in controlling cell surface plasminogen activation and extracellular proteolytic activity . . 0.94458769^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.69720354
We prove that , at 37 degrees C , the 70 kDa fragment is released into the medium , whereas the 22 kDa fragment remains bound to the cell surface . uPA complexed with its other specific inhibitor , PAI 1 , is cleaved into fragments of identical sizes , but the 70 kDa component is internalized via the alpha 2 macroglobulin receptor . 0.69720354^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :1.0535003
The activation of pro uPA to the active two chain uPA is accelerated with uPAR bound pro uPA and is achieved by plasmin and proteases of other classes like cathepsins G and L . uPAR bound uPA is susceptible to inhibition by its specific inhibitors ( PAI 1 , PAI 2 , and PN 1 ) . uPA PAI 1 and uPA PN 1 complexes , but not free uPA , are readily internalized and degraded through a mechanism that involves the multiligand receptors alpha 2 macroglobulin receptor / low density lipoprotein receptor associated protein ( alpha 2 MR ) and epithelial glycoprotein 330 ( gp 330 ) . 1.0535003^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.51710036
The `` interactive ' ' Cox model , taking into account interactions between uPA and its two inhibitors , identified a first subgroup with a very poor prognosis associating either high levels of PAI 1 with low levels of PAI 2 in the overall population as well as following stratification for axillary node negative disease , or high levels of uPA with low levels of PAI 2 in the group of menopausal women . 0.51710036^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :1.308406
The ' interactive ' model , taking into account interactions between uPA and its two inhibitors , identified a first subgroup with a very poor prognosis associating either high levels of PAI 1 with low levels of PAI 2 in the overall population and the women with no node involvement or high levels of uPA with low levels of PAI 2 in the group of menopausal women . 1.308406^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.59567761
The second order rate constant for the interaction of PAI 1 with tcr uPA , 0 . 46 10 10 ( 7 ) M 1s 1 ( pH 7 . 4 , 10 degrees C ) , ranges from 0 . 29 10 10 ( 7 ) M 1s 1 ( tcr [ KuPA > K1HPgK4HPg ] uPA ) to 1 . 08 10 10 ( 7 ) M 1s 1 ( tcr [ KuPA > K4HPgK5HPg ] uPA ) , for the tcr chimeric variants . 0.59567761^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.56414028
Downregulation of cell surface uPAR molecules in U 937 cells was detected by cytofluorimetric analysis after uPA PAI 1 and uPA PN 1 incubation for 30 min at 37 degrees C ; this effect was blocked by preincubation with the ligand of LRP / alpha 2 MR , RAP ( LRP / alpha 2 MR associated protein ) , known to block the binding of the uPA complexes to LRP / alpha 2 . 0.56414028^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.8854273
Since the inactive complex between uPA and PAI 1 can only be formed the active forms of the individual components , we have developed a sensitive and specific uPA : PAI 1 complex ELISA consisting of a sandwich format with two monoclonal antibodies ( MAbs ) against PAI 1 as capture antibodies and three biotinylated MAbs against uPA as detector antibodies . 0.8854273^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.67072679
This hypothesis is analogous to the concept proposed by Nykjaer et al in which plasminogen activator inhibitor 1 initially binds to uPA to form a complex that secondarily binds to the alpha 2 macroglobulin receptor , leading to internalization of the complex . 0.67072679^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.8216053
This mutant UPA had similar plasminogen activator characteristics as wild type UPA , including its specific activity and interaction with plasminogen activator inhibitor 1 . 0.8216053^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.95507139
An ELISA has been developed for the assessment of complexes between the urokinase type ( uPA ) and the tissue type plasminogen ( tPA ) activators with their inhibitor type 1 ( PAI 1 ) in cell culture medium and cytosolic extracts of breast tumours . 0.95507139^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.60363462
BACKGROUND : The complex between urokinase ( uPA ) and its type 1 inhibitor ( PAI 1 ) is formed exclusively from the active forms of these components ; thus , the complex concentration in a biological sample may reflect the ongoing degree of plasminogen activation . 0.60363462^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.84919524
At the cell surface , receptor ( uPAR ) bound urokinase ( uPA ) binds its inhibitor PAI 1 , localized in the matrix , and the complex is internalized by endocytic receptors , such as the low density lipoprotein receptor related protein ( LRP ) . 0.84919524^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.80200529
Moreover , a few non proteolytic functions have been ascribed to PAI 1 , mediated by its interaction with vitronectin or the interaction between the uPA PAI 1 complex bound to the uPA receptor and members of the low density lipoprotein receptor family . 0.80200529^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.67149628
With these ELISAs both complexes of the activators ( uPA , tPA ) with their inhibitor ( PAI 1 ) can be measured as a separate component . 0.67149628^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.53582937
A covalent reaction between pro uPA and PAI 1 was positively demonstrated but the reaction of PAI 1 with two chain uPA was found to be at least 1000 fold faster . 0.53582937^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.61907182
Bivariate analysis showed significant interactions between uPA and PAI 1 ( p = 0 . 0035 ) and between VEGF and PAI 1 ( p = 0 . 006 ) . 0.61907182^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.64432787
The complex between urokinase ( uPA ) and its type 1 inhibitor ( PAI 1 ) in pulmonary adenocarcinoma : relation to prognosis . 0.64432787^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.59503215
The serine protease uPA , in concert with its inhibitor PAI 1 , promotes tumor cell adhesion , migration , and proliferation , as well as extracellular matrix degradation and , thus , facilitates tumor cell invasion and metastasis . 0.59503215^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.63229764
Binding parameters [ association rate ( kass ) and dissociation rate ( kdiss ) constants , and affinity constants ( KA = kass / kdiss ) ] for the interaction between urokinase type plasminogen activator ( u PA ) and its substrate plasminogen , its inhibitor plasminogen activator inhibitor 1 ( PAI 1 ) and its receptor ( u PAR ) , were determined by real time biospecific interaction analysis ( BIA ) . 0.63229764^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.63603751
The complex between urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 ( plasminogen activator inhibitor 1 ) has been prognostically evaluated in patients with breast cancer . 0.63603751^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.73343011
Since PAI 1 binds only active , two chain u PA ( tcu PA ) , formation of the M ( r ) 100 , 000 band reflects conversion of the single chain , proenzyme form of u PA ( scu PA ) to tcu PA . 0.73343011^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.62832238
After treatment with 4 mol / L guanidinium chloride and dialysis , the largely inactive PAI 1 gained considerably in activity as judged by its reaction with low molecular weight u PA ( LMW u PA ) . 0.62832238^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :1.1878685
To isolate peptides that block the interaction between PAI 1 and u PA , phages bound to immobilized PAI 1 were eluted by incubation with u PA . 1.1878685^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MelJuso cells produced uPA as well as plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both cell lines were found to secrete uPA and PAI 1 , whereas tPA could be detected only in HS 24 conditioned media . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Ovarian follicles produce two types of plasminogen activator ( tPA and uPA ) , and their inhibitor ( PAI ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 and uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumour associated proteolytic factors uPA and PAI 1 and survival in totally resected gastric cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This was associated with increased tPA and uPA , and decreased PAI 1 in the absence of significant macrophage infiltration . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Moreover , uPA , tPA , and PAI 1 were identified in the extracts by immunoenzymatic assay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cell bound uPA is regulated by plasminogen activator inhibitor type 1 ( PAI 1 ) or type 2 ( PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Human SMC TPA , UPA , and PAI 1 antigen levels were determined by ELISAs . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TJN 950 had no effect on expression of uPA , plasminogen activator inhibitor 1 or uPA receptor mRNA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the breast carcinoma cell line MDA MB 231 , down regulation of PAI 1 and uPA mRNA by laminin was not observed . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Interestingly , urokinase ( uPA ) and its specific inhibitor PAI 1 were not up regulated . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of uPA , PAI 1 was determined by ELISA , while MMPs activity was evaluated by zymography . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of the proteolytic factors , tPA and uPA , PAI 1 and VEGF during malignant glioma progression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In both cell types , the secretion of PAI 1 was stimulated by bFGF and PDGF , as well as by uPA and tPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Pooled analysis of uPA and PAI 1 for prognosis in primary breast cancer patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Some multi nucleated giant cells were immunostained for MMP 7 and 9 , tPA , PAI 1 , uPA , and uPAR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PA , uPA , PAI 1 as prognostic factors of breast cancers ] . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
High levels of TIMP 1 and PAI 1 present in S variant reduce MMP 9 and uPA activities , respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is a major inhibitor of urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
No differences in either uPA or PAI 1 immunoreactivity were found after addition of the mAbs . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunoprecipitation with a PAI 1 monoclonal antibody confirmed that both uPA and tPA were complexed . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This activity was inhibited by plasminogen activator inhibitor 1 or antibodies to uPA but not tPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Effects of hormones on uPA , PAI 1 and suPAR from cultured endometrial and ovarian endometriotic stromal cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition , the uPA inhibitor , PAI 1 , was not affected by IL 8 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TGF beta 1 had no effect on either uPA receptor or PAI 1 in this system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of tissue PA ( tPA ) , urokinase PA ( uPA ) and PAI 1 were measured by an enzymatic immunity method . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Genetic inactivation of Mac 1 , tPA , PAI 1 or LRP but not the protease uPA abrogates macrophage migration . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Also , the expression level of TP significantly correlated with that of uPA , MMP 1 , MMP 9 , PAI 1 and VEGF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of PAI 1 were found to be correlated with those of urokinase type plasminogen activator ( u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator and its inhibitor PAI 1 in breast cancer : studies at both protein and mRNA level . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the peritoneal fluid of women with PID , PAI Ag , t PA Ag and u PA Ag were many times higher than in the control group . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This suggested a degree of sequestration and inaccessibility of membrane bound u PA of LPS activated Mo to PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Elisa tests for t PA , PAI 1 , u PA , FgDP , TDP , and D Di levels were used for measurements of fibrinolytic activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Butyrate had no effect on the production and secretion of u PA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Staining of t PA , u PA , and PAI was observed in all the metastases . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Also , mRNA for the u PA receptor and for PA inhibitor type 2 ( PAI 2 ) , but not for PAI 1 , were detected . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 was detected but did not change relative to untreated control ; u PA was undetectable in all samples . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Lp ( a ) modulated the thromboresistant cell surface by reduction of t PA and u PA , but PAI 1 remained unchanged . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrinolysis is mainly regulated by t PA , u PA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The major physiologic inhibitor of t PA and u PA is plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Subsequent fibrin autography patterns indicated the presence of u PA , PAI 1 , and t PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Transcriptional and post transcriptional effects on u PA and PAI 1 expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Furthermore , PAI 1 also inhibits u PA , attributing a role in phenomena such as cell migration and tissue remodelling . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To evaluate the role of plasminogen activators ( PAs ) in physiological angiogenesis , we have investigated the in vivo patterns of expression of urokinase type PA ( uPA ) and PA inhibitor type 1 ( PAI 1 ) during neovascularization of ovarian follicles , the corpus luteum , and the maternal decidua . ^^^ Interestingly , during corpus luteum development and decidual neovascularization , and in aortic explants , PAI 1 expression was preferentially activated in cells in the vicinity of uPA expressing capillary like structures . ^^^ These findings suggest a functional interplay between uPA and PAI 1 expressing cells and support the idea that natural PA inhibitors function during angiogenesis to protect neovascularized tissues from excessive proteolysis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In cell culture , tPA was released only from stromal cells and uPA only from glandular cells as determined by SDS PAGE followed by fibrin overlay technique , but PA inhibitor type 1 ( PAI 1 ) was secreted by both stromal and glandular cells . ^^^ The effect of the peptide hormones , hCG , GnRH , PRL , as well as cAMP in cell culture on the secretion of PAs and PAI was similar to that of estradiol , while forskolin demonstrated definitely more stimulative effect on tPA than uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 internalization / degradation is mediated by uPAR , inhibition of uPA . ^^^ Similarly , complexes of PAI 1 with low molecular mass uPA ( 33 kDa uPA ) , which lacks the uPAR binding domain , were neither bound nor degraded . ^^^ A similar result was obtained when PAI 1 was allowed to complex to uPA that had been previously bound to the receptor . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Although prourokinase was secreted in amounts sufficient to endogenously saturate trophoblast uPA receptors , trophoblasts secreted greater amounts of PAI 1 and PAI 2 than uPA , and no net plasminogen activator activity was detected in trophoblast conditioned medium . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In order to determine the mechanism by which parathyroid hormone ( PTH ) stimulates plasminogen activator ( PA ) activity in rat osteoblasts , we investigated the effect of human PTH ( 1 34 ) [ hPTH ( 1 34 ) ] on the synthesis of mRNAs for tissue type PA ( tPA ) , urokinase type PA ( uPA ) , and PA inhibitor 1 ( PAI 1 ) , and on release of PA activity and PAI 1 protein in both normal rat calvarial osteoblasts and UMR 106 01 osteogenic sarcoma cells . hPTH ( 1 34 ) ( 0 . 25 25 nM ) decreased PAI 1 mRNA and protein , and increased PA activity in both cell types in a dose dependent manner with ED 50 of about 1 nM for both responses . ^^^ Forskolin and isobutylmethylxanthine also stimulated PA activity and decreased PAI 1 protein and mRNA in both cell types . hPTH ( 1 34 ) did not show any consistent effect on tPA and uPA mRNA in calvarial osteoblasts , but a modest ( two fold ) increase of both mRNAs was observed in UMR 106 01 cells treated with 25 nM hPTH ( 1 34 ) . ^^^ The reduction of PAI 1 protein by PTH results in enhanced action of both tPA and uPA , and would contribute to the specific roles of these PAs in bone . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Colonies inducing lysis ( clone C+ and H+ ) or no lysis ( clones B and M ) were isolated and tested for mRNA levels of uPA , tPA , uPA receptor ( uPAR ) and the 3 PA inhibitors ( PAI ) , PAI 1 , PAI 2 and protease nexin 1 . ^^^ Receptor bound uPA activity was found to be considerably higher in lysis inducing than in non lysing clones and the activity was dependent on neutralization by PAI 1 rather than on the level of uPAR mRNA . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of proteins which modulate the degradative potential of these enzymes , plasminogen activator inhibitors 1 and 2 ( PAI 1 , PAI 2 ) , uPA receptor , and tissue inhibitors of metalloproteases 1 and 2 ( TIMP 1 and TIMP 2 ) , were also assayed . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of plasminogen activator and plasminogen activator inhibitor mRNA in human fibroblasts grown on different substrates . mRNA levels for urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) were examined in human diploid ( neonatal foreskin ) fibroblasts grown in 200 ml microcarrier suspension culture . ^^^ There does not appear to be any difference in uPA mRNA or in mRNA for PAI 1 or PAI 2 produced by the same cells on the four substrates . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TNF ( 100 U / ml ) treatment of endothelial cultures induced steady state levels of uPA and PAI 1 mRNA following a 18 hr treatment both 6 fold and 2 fold , respectively utilizing northern analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In breast cancer uPA and PAI 1 antigen in tumor tissue extracts are independent prognostic factors for relapse free and overall survival . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
P uPA had a low affinity for the inhibitors of plasminogen activator PAI 1 and PAI 2 , and was inhibited only by the excess amounts of inhibitors . ^^^ For PAI 1 , and the KIs of P uPA was greater and for PAI 2 , KI was higher for P uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The effect of therapeutic and pharmacological concentrations of tiaprofenic acid , a non steroidal anti inflammatory drug ( NSAID ) , on the synthesis of the plasminogen activators , urokinase plasminogen activator ( uPA ) and tissue plasminogen activator ( tPA ) , and the plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) , by human synovial membranes isolated from osteoarthritis ( OA ) and rheumatoid arthritis ( RA ) sufferers was evaluated . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is a specific inhibitor of the serine proteases tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is a specific inhibitor of the serine proteases tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have recently shown that alveolar epithelial cells may control fibrinolysis by expressing both urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Analysis of cell free conditioned medium derived from gamma IFN treated cultures by micro enzyme linked immunosorbent assay ( ELISA ) methodologies using uPA and plasminogen activator inhibitor type 1 ( PAI 1 ) specific monoclonal antibodies ( MoAbs ) indicate that the decrease in uPA activity observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis ( SDS PAGE ) zymography is a direct result of a decrease in extracellular uPA antigen and is not a consequence of increased PAI 1 antigen . ^^^ These findings are supported by Northern blot analyses that indicate that gamma IFN treatment of endothelial cells resulted in a decreased steady state level of uPA messenger RNA ( mRNA ) with no measurable change in PAI 1 mRNA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To clarify the mechanism of this suppression , we investigated the effects of dexamethasone on PA inhibitor 1 ( PAI 1 ) , tissue type PA ( tPA ) , and urokinase type PA ( uPA ) expression and also on PAI 1 protein and PA activity in both normal rat calvarial osteoblasts and a clonal osteogenic sarcoma cell line , UMR 106 01 . ^^^ Although tPA and uPA protein could not be measured , these results suggest that glucocorticoids suppress PA activity predominantly by increasing PAI 1 synthesis in rat osteoblasts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Analysis of enzymatic activity indicates that under conditions where syn uPA and std uPA are completely inhibited by endothelial type plasminogen activator inhibitor ( PAI 1 ) , mut uPA retains 90 % activity . ^^^ In identical experiments with placental type PAI ( PAI 2 ) , mut uPA retains 80 % activity . ^^^ Syn uPA is capable of forming a approximately 100 kDa complex with PAI , whereas mut uPA can not . ^^^ PAI treated mut uPA has kinetic properties similar to untreated syn uPA or std uPA . ^^^ Resistance to PAI inhibition may increase the potency of mut uPA as a thrombolytic agent . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The effects of TGF beta on synthesis of mRNA for PAI 1 and uPA were maintained when protein synthesis was inhibited , and were abolished by inhibition of RNA synthesis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Human glomerular epithelial cells ( GECs ) in culture synthesize single chain , urokinase type plasminogen activator ( SC uPA ) , tissue type plasminogen activator ( t PA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) and possess specific membrane binding sites for u PA . ^^^ Purified human alpha thrombin promoted the proliferation of GECs and induced a time and dose dependent increase of SC uPA , t PA , and PAI 1 antigens released by GECs . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A basal level of cell surface PA activity was specifically reduced by anti urokinase type PA IgG and enhanced by anti PAI 1 IgG , suggesting that the basal level is determined by a balance between uPA and PAI 1 on the cell surface . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PA inhibitor type 1 ( PAI 1 ) is an efficient inhibitor of tissue type PA ( tPA ) and urokinase type PA ( uPA ) that may therefore be instrumental for the control of plasminogen activation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Thus , by the coexpression of uPA and PAI 1 , the alveolar epithelium may actively regulate the generation of plasmin in both the normal and injured alveolus . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A short term treatment of the undifferentiated Tera 2 cells with basic fibroblast growth factor ( bFGF ) increases uPA mRNA levels and the cell associated uPA activity , whereas the secretory tPA activity decreases . bFGF induces PAI 1 mRNA expression in the undifferentiated cells , but unlike PAI 1 protein after RA treatment , the inhibitor does not accumulate around the cells but is released in the medium . ^^^ Under these conditions bFGF treatment leads to an increase in the amounts of PAI 1 and uPA mRNAs , but no changes in the localization of these components can be seen . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To assess the postulated role of plasminogen activation in tumor invasion , we have investigated the cellular sites of synthesis for urokinase type ( uPA ) and tissue type ( tPA ) plasminogen activators and their inhibitors ( PAI 1 and PAI 2 ) in two human cutaneous neoplasia that differ in their metastatic potential . ^^^ In addition , we show that SCC neoplastic cells simultaneously produce variable amounts of PAI 1 , and that PAI 1 production correlates inversely with uPA enzymatic activity . ^^^ These observations establish that invasive human malignant cells in vivo can activate plasminogen through uPA production during the early phases of tumor growth ; they also demonstrate that the proteolytic activity of tumor cells can be modulated by the concomitant production of PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of cathepsin D ( Cath D ) , urokinase ( uPA ) and two plasminogen activator inhibitors ( PAI 1 and PAI 2 ) were analysed in the cytosols of 130 human mammary tumours ( 43 benign tumours and 87 primary and unilateral breast carcinomas ) . uPA , PAI 1 and PAI 2 levels were measured by antigenic immunoassays and Cath D by immunoradiometric assay . ^^^ When Cath D , uPA , PAI 1 and PAI 2 levels in malignant tumours were compared , positive correlations were found for all combinations . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The extracellular localizations of urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) were examined in cultured bovine capillary endothelial cells ( BCEs ) by an immunofluorescence method using BCEs treated with or without saponin and focal contact preparations . ^^^ These findings suggest that uPA and PAI 1 are located under BCEs participating in the regulation of proteolytic activities provoked by plasminogen PAs plasmin system in vivo . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Gene transfer techniques were utilized to evaluate the role of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) in enhancing or preventing the expression of the invasive malignant phenotype , respectively . ^^^ Mouse L cell transfectants expressing human uPA or human PAI 1 as well as mouse B 16 transfectants expressing mouse uPA or human PAI 1 were generated . ^^^ Results from these studies provide direct evidence for an enhancing role of uPA in malignant invasion and experimental metastasis and for a modulatory role of PAI 1 in tumor cell mediated breakdown of extracellular matrices . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunocytochemistry shows a predominant localization of uPA , tPA , and PAI 1 in neuronal cells , with only a very weak positivity detectable in the few glial cells present in these cultures . ^^^ The protein kinase C ( PKC ) activator 12 O tetradecanoylphorbol 13 acetate ( TPA ) stimulates the synthesis of both uPA and PAI 1 , resulting in a final increase in the plasmin generating capacity of neuronal cell cultures . ^^^ These data represent the first characterization of the plasmin generating system in human fetal brain neurons and suggest a role for PKC in the modulation of uPA and PAI 1 synthesis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
By use of both normal and SV 40 T antigen immortalized cells , it was found that treatment with TGF beta 1 transiently increases mRNA levels for urokinase ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) approximately 5 and 50 fold , respectively , within 4 h . ^^^ A T antigen immortalized bronchial epithelial cell line that does not undergo squamous differentiation in response to TGF beta 1 but binds this growth factor did not respond to TGF beta 1 by modulation of either uPA or PAI 1 expression . ^^^ Comparison of human bronchial epithelial , pleural mesothelial , and lung fibroblastic cell strains indicated that the epithelial cells have a constitutively higher ratio of uPA to PAI 1 mRNA expression . ^^^ The induction of uPA and PAI 1 expression in human bronchial epithelial cells may be related to the ability of the cell to undergo squamous differentiation in response to TGF beta 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cultured BCEs secreted both tissue type and urokinase type PAs ( tPA and uPA ) and PAI 1 into the culture medium , and the secretion of both PAs was enhanced by the addition of bFGF . ^^^ PAI 1 complex , and the PA activity was derived mostly from uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
It has been posited that the GPI anchor facilitates clearance of uPAR bound complexes between two chain urokinase ( tcuPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) by the alpha 2 macroglobulin receptor ( alpha 2MR ) which permits re expression of unoccupied uPA receptors on the cell surface . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor type 1 ( PAI 1 ) is the rapid physiologic inhibitor of tissue type plasminogen activator and urokinase type plasminogen activator ( uPA ) . ^^^ Recombinant PAI 1 mutants were expressed in Escherichia coli and bacterial lysates assayed in duplicate for uPA inhibitory activity and vitronectin binding . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) activity has previously been shown to play a role in migration of cells into basement membranes , and it has been proposed that uPAR also is involved in this process . uPA is known to be internalized and degraded after complex formation with the inhibitor PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Secretion of PAI by migrating cells is generally stimulated by the same factors that induce uPA secretion , limiting the degradation of the matrix to the pericellular path . ^^^ On the other hand , as for uPA , tPA is inhibited by PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Because of the potential importance of plasmin generation in these processes , we evaluated the effect of elevated glucose concentrations on expression of plasminogen activator inhibitor 1 ( PAI 1 ) , tissue plasminogen activator ( tPA ) , and urokinase ( uPA ) in cultured bovine brain endothelial cells ( BBEC ) versus cultured bovine aortic endothelial cells ( BAEC ) . ^^^ A decrease in the local tissue activity of PAI 1 by elevated glucose concentrations , with no effect on tPA or uPA expression , would lead to an increase in the plasmin activity and thereby predispose neural tissues , such as the cerebrum and retina , of diabetic patients to neovascularization . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Assays for urokinase plasminogen activator type ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and the urokinase receptor ( uPAR ) were conducted . ^^^ The cell line produces uPA and PAI 1 , and also expresses uPAR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In summary , studies of the expression of fibrinolytic genes in the vessel wall suggest an active , ongoing proteolytic process , the activity of which is dependent on the relative amounts of tPA , uPA , and PAI 1 secreted and locally deposited . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recently , relative increases in the amounts of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) in tumor samples have been correlated with poorer , pathological grade , shorter disease free interval , and shorter survival . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Northern analysis of poly A+RNA prepared from cultured human mesangial cells revealed mRNA for tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and uPA receptor ( uPAR ) . ^^^ The presence of uPA protein in medium obtained from cultured human mesangial cells was demonstrated by Western blotting and ELISA which revealed a large molar excess of PAI 1 ( 1 . 2 + / 0 . 1 10 10 ( 9 ) M ) over uPA ( 1 . 2 + / 0 . 1 10 10 ( 12 ) M ) and tPA ( 0 . 19 + / 0 . 04 10 10 ( 9 ) M ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recent studies have shown that elevated levels of urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) in breast cancer correlate with an increased risk of a reduced relapse free survival time and shortened overall survival times . ^^^ The fact that plasminogen activators are indispensable for tube formation of microvascular cells and that they may induce angiogenesis in vitro strongly suggests a role for uPA and PAI 1 in tumour neovascularisation . ^^^ After obtaining tumour tissue extracts , we determined the uPA and PAI 1 levels by ELISA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The distributions of urokinase and tissue plasminogen activators ( uPA , tPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitors ( PAI 1 , PAI 2 ) were studied immunohistochemically in two subsets of colorectal adenocarcinomas with low and high aggressiveness , respectively : nine Dukes ' stage A tumors with additional other good prognostic markers and 13 Duke ' s stage C tumors with also other poor prognostic markers ( referred to as Dukes ' stage A and Dukes ' stage C tumors ) . ^^^ Both tumor groups showed accumulations of uPA , uPAR , and PAI 1 at the tumor host interface compared with the location within the tumor epithelium and the adjacent normal mucosa and muscularis propria ( all P < . 05 ) . ^^^ This may indicate that uPA in more aggressive tumors exceeds the inhibitory capacity represented by PAIs , resulting in enhanced tissue destructive potential that promotes tumor invasion . uPA and uPAR antigen levels and the uPA / PAI 1 ratio at the tumor host interface appeared to be related to tumor aggressiveness in colorectal cancer . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Previous work has shown that high levels of uPA and PAI 1 are associated with poor prognosis in primary breast cancers . ^^^ PURPOSE : In this pilot study , we explored possible associations between the expression levels of uPA or PAI 1 and the efficacy of tamoxifen treatment in breast cancer patients with relapsed disease . ^^^ METHODS : Levels of uPA , PAI 1 , estrogen receptor ( ER ) , and progesterone receptor ( PgR ) were assayed in cytosolic extracts derived from the primary breast tumors of 235 tamoxifennaive patients who had recurrent disease . ^^^ In addition , patients with uPA positive or PAI 1 positive tumors showed shorter progression free survival ( P = . 001 and P < . 05 , respectively ) and total survival after relapse ( P = . 005 and P < . 005 , respectively ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Complex formation with target proteases , tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) , caused decreased orientational freedom of BDYIA in the P 3 position , while the orientational freedom of BDYIA in position P 1 ' increased to a level similar to that of BDYIA in reactive center cleaved PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In order to determine whether the T cell lymphokines interleukin 4 ( IL 4 ) and gamma interferon ( gamma IFN ) affect SMC fibrinolysis and migration , we examined the effects of human recombinant IL 4 and gamma IFN on human aortic SMC tissue type plasminogen activator ( TPA ) , urokinase type plasminogen activator ( UPA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) antigen production , as determined by enzyme linked immunosorbent assays . ^^^ Although IL 4 had no direct effect on SMC TPA antigen , IL 4 potentiated SMC TPA antigen levels and activity in conditioned media and cellular lysates in media containing 2 % fetal bovine serum but did not change UPA or PAI 1 production . gamma IFN attenuated IL 4 augmentation of SMC TPA antigen production in conditioned media , although gamma IFN itself had no direct effects on SMC TPA and PAI 1 antigen production . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS AND RESULTS : Experimental measurements of cardiac output , heart rate , tissue plasminogen activator ( TPA ) , urokinase plasminogen activator ( UPA ) , plasminogen activator inhibitor ( PAI 1 ) , C 1 inhibitor , and TPA / C1 inhibitor complex during the infusions and exercise were used to develop a comprehensive fluid phase model of the circulatory regulation of fibrinolysis . alpha and beta adrenergic agonists increased TPA and UPA in plasma by different mechanisms : Phenylephrine decreased hepatic blood flow and thus clearance while isoproterenol stimulated increased secretion of TPA and UPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The presence of mRNA for the uPA receptor ( uPAR ) has been demonstrated in these cells and steady state levels shown to be greatly enhanced , the response being rapid and sustained for at least 24 hours . mRNA for plasminogen activator inhibitor 1 ( PAI 1 ) was modulated in a biphasic manner , with inhibition of the constitutive level apparent at 4 hours of treatment and stimulation apparent at 12 hours and longer , while PAI 1 protein , measured by an ELISA assay for rat PAI 1 , was diminished over this period . ^^^ Although it was not possible to measure uPAR number and affinity it seems likely that elevated uPAR mRNA would translate into increased uPARs which would localize the increased uPA activity to the pericellular region . tPA mRNA and activity were also increased transiently with the activity inhibited with prolonged incubations , apparently by PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Regarding the components of the PA system , we found differences in expression of urokinase type PA ( uPA ) and type 1 and 2 PA inhibitors ( PAI 1 and 2 ) between metastasizing and nonmetastasizing cell lines . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both uPA and its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) , were overexpressed in the HPV 16 transformed cells relative to the parental cell line . ^^^ The transformed cells , but not the parental cells , were able to degrade and penetrate the Matrigel membrane and penetration was blocked by both PAI 1 and by antibodies to uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) inhibited PA activity of preformed uPA / uPAR complexes and increased cycling of the receptor from the cell surface . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) inhibited PA activity of preformed uPA / uPAR complexes and increased cycling of the receptor from the cell surface . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TS 1 expression resulted in a > 100 fold decrease in net fibrinolytic ( urokinase type plasminogen activator , uPA ) activity due to more plasminogen activator inhibitor 1 and less uPA secretion . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Thus , the concentration of PAI 1 in the stromal cell conditioned medium at the end of 0 3 days exceeded those of tPA and uPA , respectively , by 28 and 12 fold in response to MPA and by 52 and 25 fold in response to E 2 plus MPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PATIENTS AND METHODS : In a consecutive series of 203 patients resected for primary gastric cancer , the expression of uPA , uPA receptor ( uPA R ) , plasminogen activator inhibitor ( PAI ) 1 , and PAI 2 was determined immunohistochemically . ^^^ RESULTS : Univariate analyses revealed a highly significant inverse correlation of uPA , uPA R , and PAI 1 expression with survival time ( P = . 0008 , P = . 0002 , and P = . 0002 , respectively ) , whereas PAI 2 demonstrated only a weak correlation . ^^^ In pT1 / 2 tumors and in Laurn ' s diffuse and mixed types , uPA , uPA R , and PAI 1 added significant prognostic information . ^^^ CONCLUSION : PAI 1 , uPA , and uPA R are new functional risk factors reflecting clinical prognosis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) are produced by osteoblasts , as are the specific inhibitor plasminogen activator inhibitor 1 ( PAI 1 ) and a cellular receptor for uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Additionally , uPA and PAI 1 assay results suggest that 4 HPR may impair active uPA ' s proteolytic activity while upregulating the expression of total activatable uPA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The relevance of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor ( PAI ) type 1 in predicting the survival probability of patients with advanced ovarian cancer after radical surgery and adjuvant chemotherapy by assessing the patients ' primary tumors has recently been shown by us ( W . ^^^ In the present study , we determined uPA , uPA receptor , PAI 1 , and PAI 2 concentrations in primary tumors and tumor infiltrated omentum and retroperitoneal lymph nodes of ovarian cancer patients . ^^^ In metastases of the omentum from ovarian cancer stage FIGO IIIc or 4 patients , we noted a 4 fold elevated uPA content , a 2 fold increase in PAI 1 , and also a significant increase in uPA receptor and PAI 2 over primary tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Butyrate was found to induce a rapid and transient increase in plasminogen activator inhibitor type 1 ( PAI 1 ) mRNA while concomitantly suppressing the constitutive production of both urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) mRNA transcripts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
By immunohistochemistry , we studied the expression of PAs ( tPA and uPA ) , their major physiological inhibitor ( PAI 1 ) , and a receptor for uPA ( uPAR ) in human coronary arteries with either pure fibrointimal proliferation ( n = 15 ) or developed atherosclerotic plaques ( n = 10 ) . ^^^ Overall , the degree of staining showed the following rank order : PAI 1 > tPA > uPAR > uPA . ^^^ However , the ratio of intimal to medial expression of tPA ( P = . 001 ) and uPAR ( P = . 004 ) was significantly increased in atherosclerotic arteries , with a similar trend for uPA ( P = . 069 ) but not for PAI 1 ( P = . 73 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Using type 2 pneumocytes , endocytosis of a previously described gp 330 ligand , urokinase ( uPA ) complexed with plasminogen activator inhibitor 1 ( uPA : PAI 1 ) and two new ligands , PAI 1 and pro uPA , was demonstrated . ^^^ In addition , gp 330 acts in concert with LRP in type 2 pneumocytes to mediate clearance of a variety of proteins involved in plasminogen activation , including uPA : PAI 1 complexes PAI 1 and pro uPA . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Analysis of cell free conditioned medium obtained from PKC inhibitor treated cultures by micro enzyme linked immunosorbent assay methodologies using uPA and plasminogen activator inhibitor type 1 ( PAI 1 ) specific monoclonal antibodies indicate that the decrease in uPA activity observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis zymography was a direct result of decreased extracellular uPA antigen and not a consequence of increased PAI 1 antigen . ^^^ The effect of PKC inhibitors was specific for TNF mediated increased uPA expression because cytokine induction of PAI 1 was not influenced by these agents . ^^^ Northern blot analyses also showed that PKC inhibitor treatment of endothelial cells resulted in a decreased steady state level of uPA mRNA with no measurable change in PAI 1 mRNA in cultures incubated with TNF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
DESIGN : Immunohistochemical localization of urokinase type PA ( uPA ) , tissue type PA ( tPA ) , type 1 PAI ( PAI 1 ) , and type 2 PAI ( PAI 2 ) in four normal lung biopsy specimens and in four adenocarcinomas ( AC ) , four squamous carcinomas ( SC ) , two large cell carcinomas ( LCC ) , and ten small cell carcinomas ( SCC ) biopsy specimens . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The relative topographical distribution of urokinase type plasminogen activator ( uPA ) , tissue type PA ( tPA ) , PA inhibitor 1 ( PAI 1 ) , PA inhibitor 2 ( PAI 2 ) , plasmin ( ogen ) , alpha 2 antiplasmin , and alpha 2 macroglobulin was studied in lesional epidermis of psoriasis vulgaris , and in normal epidermis , by immunohistochemistry . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Previous work has shown that LRP is responsible for mediating the internalization of urinary type plasminogen activator ( uPA ) complexed to plasminogen activator inhibitor type 1 ( PAI 1 ) ( Nykjaer et al . , 1992 ; Herz et al . , 1992 ) . ^^^ The binding of 125I pro uPA to LRP is blocked by the 39 kDa receptor associated protein , but not by an amino terminal fragment of uPA , which is known to block binding of uPA to the urokinase receptor . 125I Pro uPA can be internalized and degraded by Hep G 2 cells independent of PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Therefore , we assessed the effects of RU 486 administration on the expression of immunoreactive ( ir ) endometrial stromal cell urokinase type ( uPA ) and tissue type ( tPA ) plasminogen activator and their activities as well as levels of ir type 1 plasminogen activator inhibitor ( PAI 1 ) using a well characterized in vitro model of decidualization . ^^^ Compared to the vehicle control , E 2 and RU 486 used alone had no effect on levels of ir PAI 1 , uPA , or tPA or on PA activity in the conditioned medium . ^^^ In contrast , MPA and E 2 plus MPA decreased ir uPA and tPA levels and their corresponding activities , whereas MPA increased , and E 2 plus MPA further increased ir PAI 1 release . ^^^ To determine if RU 486 reversed progestin inhibited stromal cell uPA and tPA release and progestin enhanced PAI 1 expression , confluent cultures were exposed to 10 ( 8 ) mol / L E 2 plus 10 ( 7 ) mol / L MPA for 10 days , washed , and reexposed to E 2 plus MPA , steroid free medium , or RU 486 for 3 5 or 9 11 days . ^^^ Compared with cultures maintained in E 2 plus MPA for 3 5 days , withdrawal to a steroid free medium failed to affect stromal cell ir PAI 1 , uPA , or tPA levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary inhibitor of the plasminogen activators ( PAs ) , tissue type plasminogen activator ( tPA ) , and urokinase type plasminogen activator ( uPA ) . ^^^ Several PAI 1 variants that were inactive against uPA in a previous study ( Sherman , P . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary inhibitor of the plasminogen activators ( PAs ) , tissue type plasminogen activator ( tPA ) , and urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The proteolytic activity of uPA is modulated by its cell surface receptor , as well as by plasminogen activator inhibitor type 1 ( PAI 1 ) and , to a lesser degree , by other inhibitors . ^^^ Our findings indicate that uPA and PAI 1 expression are dramatically upregulated in malignant brain tumors in parallel with the histological progression of the tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of plasminogen activators ( uPA and tPA ) and their inhibitors ( PNI and PAI 1 ) were determined by fibrin zymography , ELISA , amidolytic activity assay , complex formation , and Western blot analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of uPA and its inhibitor PAI 1 in tumor extracts have previously been demonstrated to be of prognostic value in breast cancer as well as other types of cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this investigation we show that uPAR levels correlate with uPA levels in human breast cancers . uPAR levels , however , do not correlate with other components of the plasminogen activator system such as tissue type plasminogen activator ( t PA ) , PAI 1 or PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Therefore , the enhancement of plasmin activity in the conditioned medium was dependent on increased uPA activity via the decrease of the PAI 1 level of Gin 1 cells treated with C . rectus LPS . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Additionally , we have measured the release of urokinase ( uPA ) , tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) into the cell culture media . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrinolytic activity was inhibited by actinomycin D and cyclohexamide , but changes in mRNAs for uPA , tPA , PAI 1 , and TF by either cytokine were not appreciable . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Three of these cell lines co expressed the plasminogen activator inhibitor PAI 1 in addition to uPA . ^^^ Assays for invasiveness revealed 4 cell lines capable of traversing a Matrigel barrier , including the 3 which co expressed uPA , PAI 1 and uPA receptor . ^^^ Based on these observations , we hypothesized that both uPA and PAI 1 might be important for invasion by lung tumor cells , at least in vitro . ^^^ We therefore tested polyclonal antibodies which inhibit uPA and PAI 1 activity for their effects on the highly invasive H 292 cell line . ^^^ After 3 days , invasive capacity was inhibited by antibodies to both uPA and PAI 1 in a dose dependent manner . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase ( uPA ) and PAI 1 predict survival in advanced ovarian cancer patients ( FIGO 3 ) after radical surgery and platinum based chemotherapy . ^^^ The tumor associated protease urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 were detected in malignant ovarian cancer tissue extracts . ^^^ According to a cutoff value for uPA and PAI 1 , patients could be subdivided into risk groups : patients with low uPA and PAI 1 ( uPA < 0 . 9 ng / mg protein and PAI 1 < 13 . 5 ng / mg protein ) had a statistically significant better prognosis than patients with high uPA and / or high PAI 1 ( P = 0 . 01 ) . ^^^ Especially in patients without residual tumor , uPA and PAI 1 were strong prognostic parameters ( P = 0 . 03 ) . ^^^ In multivariate analysis the residual tumor was the most powerful prognostic indicator ( P = 0 . 013 ) closely followed by uPA and PAI 1 ( P = 0 . 047 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Complex formation with uPA had no effect on the fluorescence spectrum of P18cys NBD while the spectrum of P3cys NBD revealed changes consistent with a restriction of the mobility of NBD probe in the uPA PAI 1 complex . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The present study evaluate both the expression and release of PAs ( uPA and tPA ) and PAIs ( PAI 1 and PAI 2 ) from cultured cells , and also the expression of uPA receptor ( uPAR ) . ^^^ LOX released tPA ( median 9 ng / million cells at 72 hours ) , PAI 1 ( 1050 ng / million cells ) and PAI 2 ( 245 ng / million cells ) , and fibroblasts released uPA ( 1 ng / million cells ) and PAI 1 ( 910 ng / million cells ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The antigen levels of urokinase type plasminogen activator ( uPA ) and its inhibitor plasminogen activator inhibitor ( PAI ) 1 , as detected in tumor extracts by ELISA , have been reported to be correlated with a poor prognosis in primary breast cancer . ^^^ We determined PAI 2 antigen levels along with those of uPA and PAI 1 in 1012 routinely prepared tumor cytosols of patients with primary breast cancer ( median follow up , 71 months ) . ^^^ In the overall population there was no significant association between the level of PAI 2 and prognosis , while in tumors with high uPA values , PAI 2 ( test for trend ) was associated with a prolonged relapse free survival , metastasis free survival , and overall survival ( for all analyses , P < 0 . 02 ) . ^^^ In Cox ' s multivariate analysis for relapse free survival , metastasis free survival , and overall survival in tumors with high uPA values ( including patient ' s age , menopausal status , lymph node status , tumor size , estrogen and progesterone receptor status , uPA , and PAI 1 ) , PAI 2 either dichotomized or , as a continuous variable , was independently associated with a favorable relapse free survival , metastasis free survival , and overall survival . ^^^ We speculate that PAI 2 may serve as an inhibitor for uPA in human primary breast cancers . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The effects of calcium on human foreskin keratinocyte expression of urokinase type ( uPA ) and tissue type ( tPA ) plasminogen activator enzymes and plasminogen activator inhibitor 1 and 2 ( PAI 1 , PAI 2 ) were assessed by Northern analyses . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Thus , uPA bound to monocyte / macrophages and its interactions with plasminogen activator inhibitors types 1 and 2 ( PAI 1 and PAI 2 ) may modify atherogenesis by altering cell associated proteolytic activity , degradation of ECM , and neointimal formation at sites of vascular injury . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A high concentration of glucose alters the production of tPA , uPA and PAI 1 antigens from human mesangial cells . ^^^ To elucidate a role of tPA , uPA and PAI 1 for the development of diabetic glomerulosclerosis , the effect of high glucose concentration on the production of both basal and thrombin mediated tPA , uPA and PAI 1 antigens from human mesangial cells was investigated . ^^^ Thrombin stimulated dose dependently the production of tPA , uPA and PAI 1 from the cells grown in either 5 or 33 mM glucose . ^^^ However , the magnitude of the increase in tPA , uPA and PAI 1 from the cells grown in high glucose was less than that in normal glucose . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The alpha 2 macroglobulin receptor / low density lipoprotein receptor related protein ( alpha 2MR / LRP ) binds several ligands , including complex between the two chain urokinase type plasminogen activator ( uPA ) and type 1 plasminogen activator inhibitor ( PAI 1 ) , and the single chain zymogen pro urokinase ( pro uPA ) . ^^^ We have used truncated variants of uPA and PAI 1 as well as Fab fragments of monoclonal antibodies with known epitopes to identify regions in the uPA . ^^^ PAI 1 complex and in pro uPA involved in binding to alpha 2MR / LRP . uPA . ^^^ PAI 1 complex bound with high affinity ( EC 50 about 0 . 4 nM ) via contacts in the PAI 1 moiety as well as the uPA serine proteinase domain and the uPAA chain . ^^^ PAI 1 and pro uPA at the cell surface , and since it has been demonstrated that urokinase receptor bound uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both pro uPA and uPA : PAI 1 complex bind to the alpha 2 macroglobulin receptor / LDL receptor related protein . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) and its type 1 inhibitor ( PAI 1 ) : regulators of proteolysis during cancer invasion and prognostic parameters in breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Steady state levels of mRNA for PAI 1 were also decreased by 1 , 25 ( OH ) 2D3 in a dose dependent manner , without significant effects on mRNA for either tissue type PA ( tPA ) or urokinase type PA ( uPA ) . ^^^ In osteoblast like cells however , 1 , 25 ( OH ) 2D3 and PTH actions differed , in that 1 , 25 ( OH ) 2D3 had no effect on either PAI 1 or uPA mRNA levels under conditions of protein synthesis inhibition , whereas PTH decreased PAI 1 , and increased uPA mRNA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The activity of uPA on the cell surface appears to be a function of the number of uPA specific receptors ( uPAR ) and the extent of inhibition of uPA by plasminogen activator inhibitors ( PAI ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The present study was undertaken to assess the role of tumor associated urokinase type plasminogen activator ( uPA ) and its inhibitor type 1 ( PAI 1 ) as a predictor for early relapse and poor prognosis in patients with stage 2 cervical cancer of the uterus . ^^^ We have investigated the localization of uPA and PAI 1 immunohistochemically in formalin fixed paraffin embedded tissue sections . uPA and PAI 1 were analyzed antigenically , enzymologically , and zymographically in 28 patients with pelvic lymph node involvement and in 34 cases without nodal spread , as well as in 10 cases with normal cervix . ^^^ In cancer tissues , strong staining for uPA was found in areas with invasive growth and degradation of surrounding normal tissue , while most tumor nests showed a mild or a moderate , evenly distributed PAI 1 staining . ^^^ A significantly higher lymph node positive rate was observed in patients having tumors with strong uPA and / or PAI 1 stainings than in those with tumors with weak stainings . ^^^ In spite of significantly higher PAI 1 levels in the primary neoplastic tissues , uPA was found to be increased as well , both in antigen level and in activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Receptor bound uPA may be inhibited by the specific inhibitors PAI 1 and PAI 2 , and the complex thus formed may subsequently be internalized and degraded in lysosomes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
After binding to its receptor ( uPAR ) , active cell surface urokinase ( uPA ) is not internalized while the complex formed by uPA with plasminogen activator inhibitor type 1 ( PAI 1 ) is internalized and degraded . ^^^ PAI 1 , the internalization of uPA . rPN 1 also required alpha 2 MR , since it could be inhibited by the 39 kDa alpha 2 macroglobulin receptor / low density lipoprotein receptor associated protein , a ligand for the alpha 2 MR . ^^^ PAI 1 but unlike free uPA , bound specifically to both uPAR and alpha 2 MR . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Northern blot analysis demonstrated expression of urokinase type plasminogen activator ( uPA ) , tissue type PA ( tPA ) and PA inhibitor 1 ( PAI 1 ) in some of the above cell lines . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : Evaluation of the relationship between plasminogen activator inhibitor 1 ( PAI 1 ) and the metastatic potential of primary breast cancer , and to compare the prognostic impact of PAI 1 in multivariate analysis with those of conventional prognostic factors , including steroid hormone receptors , and those of urokinase plasminogen activator ( uPA ) , pS 2 protein ( PS 2 ) , and cathepsin D . ^^^ Estrogen receptor ( ER ) and progesterone receptor ( PgR ) status were assessed by radioligand binding assay , PS 2 , and cathepsin D by radiometric immunoassay , and uPA and PAI 1 by enzyme linked immunosorbent assay ( ELISA ) . ^^^ Relating the levels of PAI 1 with those of other cytosolic prognostic factors , we found a positive association with the metastasis related proteases uPA ( P < . 0001 ) and cathepsin D ( P < . 0001 ) . ^^^ In multivariate regression analysis for 5 year relapse free survival , and using an optimized cutoff point for discrimination between PAI 1 positive and negative , independent predictors of the rate of relapse were found to be PAI 1 ( P < . 0001 ) and uPA ( P = . 01 ) of the cytosolic parameters , and tumor size , lymph node status , and premenopausal age of the clinical parameters . ^^^ In patients with node positive disease , PAI 1 ( P < . 001 ) , uPA ( P = . 02 ) , tumor size ( P < . 001 ) , and the number of positive lymph nodes ( P < . 001 ) were all positively associated with the rate of relapse . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We assayed urokinase plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) in 43 human brain tumors ( predominantly astrocytic gliomas ) and in histologically disease free brain tissue resected with 21 of the tumors . ^^^ Levels of uPA , tPA , and PAI 1 , measured by enzyme linked immunosorbent assay , varied widely among individuals in neoplastic and in normal tissue but did not correlate with age or sex . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have studied the prognostic value of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and type 1 plasminogen activator inhibitor ( PAI 1 ) in tumor extracts from 84 patients with squamous cell lung carcinoma and 38 patients with large cell lung carcinoma , measuring each molecule with sandwich enzyme linked immunosorbent assays . ^^^ High uPAR levels were significantly associated with short overall survival in patients with squamous cell lung carcinomas when the median value was used as a cutoff point ( P = 0 . 038 ) , while no statistically significant prognostic impact of uPA and PAI 1 levels was found in this group of patients . ^^^ There was a positive correlation between uPAR and PAI 1 levels in both groups and between uPA and uPAR levels in the large cell carcinoma patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , HRMEC produced urokinase type plasminogen activator ( uPA ) in a 24 fold excess to PAI 1 and were thereby profibrinolytic with regard to fibrinolysis antigen expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Arterial and coronary sinus blood were sampled concomitantly before cardioplegia and after release of the aortic cross clamp , for measurement of t PA antigen ( Ag ) and activity , plasminogen activator inhibitor ( PAI 1 ) Ag and activity , t PA / PAI 1 complex , single chain urokinase ( sc uPA ) and urokinase ( uPA ) plasminogen activators , the fibrin split product D dimer , thrombin antithrombin complex ( TAT ) , and the prothrombin split product F 1 + 2 . ^^^ Cardiopulmonary bypass significantly increased t PA Ag and activity , t PA / PAI complex , D dimer , TAT , and F 1 + 2 , and decreased PAI 1 Ag and activity in arterial blood ; uPA and sc uPA were unchanged . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 , which is a natural inhibitor of tumor cell associated urokinase type plasminogen activator ( uPA ) activity , inhibited activation of plasminogen to plasmin in the growth media , thereby preventing plasmin induced detachment of cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Approximately 40 % of the PAI 1 secreted is biologically active as judged by the formation of higher molecular weight , SDS resistant complexes with urokinase plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The two types of plasminogen activator , tissue type ( tPA ) and urokinase type ( uPA ) , are produced by osteoblasts , as is the specific PA inhibitor , PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The serpins we analyzed were protease nexin 1 ( PNI ) , PA inhibitor 1 ( PAI 1 , and the kallikrein binding protein ( KBP ) . uPA nearly doubled 48 h after injury , while there was no change in amidolytic activity after addition of fibrin monomer as an estimation of tPA activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , a member of the serine protease inhibitor ( Serpin ) superfamily , is the primary inhibitor of the plasminogen activators tPA and uPA . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) , a member of the serine protease inhibitor ( Serpin ) superfamily , is the primary inhibitor of the plasminogen activators tPA and uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The high uPA activity was counteracted both in the growth medium and at the cell surface by an increased plasminogen activator inhibitor ( PAI ) production and reduction of uPA synthesis . ^^^ The expression of uPA receptor and PAI 2 were stimulated and persisted at 48 hours from RA addition . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The tissue ( tPA ) and urokinase ( uPA ) types of plasminogen activator and the plasminogen activator inhibitor 1 ( PAI 1 ) are enzymatic proteins that may play an important role in the degradation of the extracellular matrix in physiologic and neoplastic conditions . ^^^ We have studied the immunohistochemical distribution of tPA , uPA , and PAI 1 in 24 human gliomas , including seven well differentiated astrocytomas , three oligodendrogliomas , six anaplastic astrocytomas , and eight glioblastomas multiforme . ^^^ Endothelial cells of vessels in non neoplastic and neoplastic brain were immunoreactive for tPA , but not for uPA or PAI 1 . ^^^ Non neoplastic glia were unreactive for tPA , uPA , and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Seminal plasma ( N = 10 ) collected in the absence of extrinsic inhibitors had a mean of 25 + / 5 ng / ml uPA : PCI , 76 + / 23 ng / ml tPA : PCI , and 4 + / 2 ng / ml of tPA complexes with plasminogen activator inhibitor 1 ( tPA : PAI 1 ) . 93 % of the uPA and 17 % of the tPA antigen in seminal plasma was in complex with PCI and , when complexation was inhibited by collecting semen into an 1 , 10 phenanthrolinium solution , 33 % of the uPA and 7 % of the tPA was complexed to PCI . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Furthermore , PAI 1 and uPA are moderately correlated with each other ( uPATx versus PAI 1Tx : R = 0 . 40 ; uPAcyt versus PAI 1cyt : R = 0 . 39 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Regulation of endothelial cell ( EC ) plasminogen activator inhibitor type 1 ( PAI 1 ) , the primary physiological inhibitor of tissue type plasminogen activator ( TPA ) and urokinase type plasminogen activator ( UPA ) , by various stimuli has been well characterized . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The prognostic impact of the proteolytic factors urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) was evaluated in 76 completely resected gastric cancer patients enrolled in a prospective study . ^^^ All patients underwent macroscopically and microscopically residual tumor free resection ( category R 0 , Union International Contre Cancer , 1987 ) . uPA and PAI 1 levels were quantified in detergent extracted ( Triton 10 100 ) specimens of primary gastric tumors by enzyme linked immunosorbent assays . ^^^ For PAI 1 , 0 . 93 ng PAI 1 / mg protein versus 0 . 09 ng PAI 1 / mg protein was calculated . uPA levels in tumor tissue extracts were significantly correlated with vascular invasion , Laurn classification , and WHO classification , whereas PAI 1 levels showed a significant correlation with advanced lymph node involvement , depth of invasion , tumor stage , site of tumor , and the Laurn , Borrmann , and WHO classifications . ^^^ Elevated uPA and PAI 1 levels were found to be associated with poor prognosis . ^^^ The optimal cutoff values indicating a group of patients with shorter survival were 1 . 5 ng uPA / mg protein and 1 . 25 ng PAI 1 / mg protein , respectively ( Classification and Regression Tree analysis ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These lines were then analyzed to determine the specific protein ( s ) responsible for differences in PA activity . mRNA and protein levels of cellular uPA , tPA , PAI 1 and PAI 2 were measured using Northern blot analysis and ELISA assays . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
As determined by histopathological methods , the malignant tumors showed statistically significantly higher expression of urokinase plasminogen activator ( uPA ) , type 1 plasminogen activator inhibitor ( PAI 1 ) , and especially urokinase plasminogen activator receptor ( uPAR ) than benign tissues . ^^^ When the tumors express high amounts of uPA , they express a high amount of uPAR in 50 % of cases and PAI 1 in 57 . 3 % of cases . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Patient samples and plasma from 25 normal controls were assayed for tPA activity , PAI 1 activity , and urokinase ( uPA ) activity and antigen . tPA activity and antigen were not significantly different in patients than in controls . ^^^ PAI 1 activity was significantly greater in patients ( P < 0 . 0001 ) . uPA activity was not different in the two groups . ^^^ These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI 1 activity but also by reduced total uPA concentration . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have studied the prognostic value of urokinase type plasminogen activator ( uPA ) and type 1 plasminogen activator inhibitor ( PAI 1 ) in tumor extracts from 106 patients with adenocarcinoma of the lung . uPA and PAI 1 levels were determined by sandwich enzyme linked immunosorbent assays . ^^^ No correlation was found between uPA and PAI 1 ( r = 0 . 23 ) . ^^^ High PAI 1 levels were significantly associated with short duration overall survival ( P = 0 . 017 ) , while uPA levels showed no significant association with overall survival . ^^^ The prognostic impact of uPA and PAI 1 were investigated together with other prognostic factors in Cox multivariate analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Active PAI 1 inhibited the tumor cell surface receptor bound uPA activity . ^^^ When SMT ccl cells saturated with uPA PAI 1 complexes were treated with a 50 fold molar excess of APC , PAI 1 APC complex was demonstrated in conditioned medium , indicating that PAI 1 was dissociated from receptor bound uPA on tumor cells and that tumor cell associated uPA restored its enzymatic activity . ^^^ Although APC alone had no effect on tumor cell invasion , the addition of APC to the cells saturated with uPA PAI 1 complexes showed regeneration of tumor cell surface receptor bound uPA activity and produced substantial and efficient invading effects . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This invasive and tumorigenic cancer cell line expresses uPA , its inhibitor PAI 1 , and the high affinity receptor for uPA , uPAR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , we determined the plasma levels of tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor ( PAI ) , urokinase plasminogen activator ( uPA ) , and von Willebrand factor ( vWF ) antigen in Blackfoot disease patients , in comparison with normal controls from non endemic areas and the endemic area , Putai . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present report , we describe that affinity purified gp 330 from rabbit renal cortex binds plasminogen activator inhibitor type 1 ( PAI 1 ) complexed with urokinase type plasminogen activator ( uPA ) . alpha 2M methylamine , which binds with high affinity to alpha 2MR / LRP , did not bind to gp 330 . ^^^ PAI 1 complexes in tubules was abolished by excess unlabeled rRAP , and a rRAP inhibitable endocytosis and degradation of labeled uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The balance between pro and anti fibrinolytic activities was quantitatively changed in the murine macrophages after the injection of thioglycollate . uPA like materials were synthesized by the macrophages and secreted to the conditioned medium continuously , while PAI activity was unchanged during the same time period . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast to the differing effects of TGF beta on cell growth , we found that all these cell types showed strong induction of most of the mRNA and protein species examined , including fibronectin , collagen 4 , laminin , type 4 collagenase , urokinase type plasminogen activator ( uPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This difference was largely due to cell surface turnover of active uPA complexed with plasminogen activator inhibitor ( PAI ) . ^^^ These data indicate that cytokines prime monocyte progenitors for uPA receptor mediated signals leading to adherence , continued uPA receptor occupancy is required for adherence , and PAI decreases adherence by promoting clearance of uPA / PAI complexes . ^^^ Thus the interaction of uPA and PAI at the cell surface , known to affect extracellular matrix proteolysis and hence myeloid cell migration , also regulates adhesion . ^^^ The coordinated regulation of these two uPA functions by PAI may enhance the migratory potential of monocytic cells . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The prognostic value of urokinase type plasminogen activator ( uPA ) and type 1 plasminogen activator inhibitor ( PAI 1 ) levels in cytosolic extracts of ductal breast carcinomas was studied , retrospectively , in 118 premenopausal and 72 postmenopausal high risk patients entered into the protocol of Danish Breast Cancer Cooperative Group trials for adjuvant treatment of breast cancer . ^^^ The median observation time was 8 . 5 years . uPA and PAI 1 levels were determined by sandwich enzyme linked immunosorbent assays . ^^^ Univariate analysis showed that a high uPA level is significantly associated with short overall survival in both premenopausal ( P < 0 . 001 ) and postmenopausal ( P = 0 . 03 ) patients , while a high PAI 1 content significantly predicts shorter overall survival in premenopausal ( P = 0 . 005 ) and postmenopausal ( P < 0 . 001 ) patients and shorter relapse free survival in postmenopausal patients ( P < 0 . 001 ) . ^^^ When the levels of uPA and PAI 1 are related to those of other prognostic parameters , both high uPA and high PAI 1 levels are associated with grade of anaplasia in premenopausal patients and with number of tumor positive lymph nodes in postmenopausal patients . ^^^ The prognostic value of uPA and PAI 1 levels was compared with that of established prognostic parameters by multivariate analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have demonstrated for the first time that ( 1 ) mouse Sertoli cells predominantly secrete tPA under the action of FSH and cAMP generating agents , whereas Leydig cells mainly produce uPA ; ( 2 ) Sertoli cells are also capable of secreting PAI 1 , as well as FSH , growth factors and GnRH increase PAI 1 gene expression ; ( 3 ) the increases in tPA and PAI 1 activities by different hormones in the conditioned media of Sertoli cells correspond to the increases in the levels of tPA and PAI 1 mRNA in the cultured cells , suggesting that the synthesis of the activator inhibitor in mouse Sertoli cells is regulated at a transcriptional level and the tPA secreted by Sertoli cells may be involved in the spermatogenesis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase ( uPA ) and its inhibitor PAI 1 are strong and independent prognostic factors in node negative breast cancer . ^^^ We used enzyme linked immunoassays ( ELISA ) to test for uPA antigen and its inhibitor PAI 1 in tumor tissue extracts of 247 breast cancer patients who were enrolled in a prospective study . ^^^ The major new finding is that breast cancer patients with either high uPA ( > 2 . 97 ng / mg protein ) or high content of the uPA inhibitor PAI 1 ( > 2 . 18 ng / mg protein ) in their primary tumors have an increased risk of relapse and death . ^^^ In node negative patients the impact of uPA is closely followed by that of PAI 1 . ^^^ Since uPA and PAI 1 are independent prognostic factors , the node negative patients could be subdivided further by combining these two variables . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor type 1 ( PAI 1 ) , the physiologic inhibitor of both tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) , is a major biosynthetic product of endothelial cells in vitro ; endothelial cells in vivo , in contrast , do not appear to produce significant amounts of PAI 1 as made evident by in situ hybridization studies in normal mice . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Methods used to assess the expression and levels of urokinase type plasminogen activator ( uPA ) or plasminogen activator inhibitor 1 ( PAI 1 ) have also been developed , and correlate with angiogenic activity and prognosis of patients with breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Three major components of the plasminogen activators ( PA ) / plasmin system are synthesized physiologically in glomeruli , and can be involved in glomerular proteolysis and extracellular matrix metabolism : tissue type PA ( tPA ) , urokinase ( uPA ) and PA inhibitor type 1 ( PAI 1 ) . ^^^ RNase protection assays and in situ hybridizations revealed a marked glomerular induction of PAI 1 mRNA abundance without any significant changes in renal tPA and uPA mRNA levels in the two different types of lupus like glomerulonephritis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both calcium mobilizing agents induced at 18 hours a dose dependent accumulation of PAI 1 in culture medium , whereas uPA was not affected . ^^^ TNF alone induced a more marked accumulation of PAI 1 than of uPA . ^^^ Association of TNF with the agents induced a PAI 1 response that was more than additive of the two , whereas the secretion of uPA was not enhanced . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Therefore , we evaluated whether thrombin affected the expression of endometrial stromal cell urokinase type ( uPA ) and tissue type ( tPA ) plasminogen activators and their primary inhibitor , type 1 plasminogen activator inhibitor ( PAI 1 ) , and whether ovarian steroids modulated putative thrombin effects . ^^^ The conditioned medium was then collected and analyzed for immunoreactive ( ir ) uPA , tPA , and PAI 1 by enzyme linked immunosorbent assay and for PA activity by chromogenic assay , whereas Northern analysis of the cells was employed to evaluate the expression of thrombin receptor , uPA , tPA , and PAI 1 messenger ribonucleic acid ( mRNA ) species . ^^^ Thrombin added in the absence of exogenous steroids elevated concentrations of ir tPA , uPA , and PAI 1 compared with control cultures . ^^^ Conversely , in the absence of added thrombin , MPA added alone or together with E 2 inhibited levels of ir tPA and uPA while stimulating PAI 1 levels despite the lack of a response to E 2 alone . ^^^ Interestingly , thrombin counteracted this progestin inhibition of tPA and uPA expression and augmented the progestin enhanced expression of PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A strong independent prognostic value ( relapse free and / or overall survival ) has especially been demonstrated for uPA and its inhibitor PAI 1 in patients with cancer of the breast , ovary , stomach , esophagus , colon , lung , and kidney thus predicting the course of the cancer disease . ^^^ The strong correlation between elevated uPA and / or PAI 1 values in primary cancer tissues and the malignant phenotype of cancer cells has prompted to explore new tumor biology oriented concepts in order to suppress uPA or uPA receptor ( CD 87 ) expression or to abrogate interaction of uPA with CD 87 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS AND RESULTS : Enzyme immunoassays ( EIAs ) showed that urokinase and tissue plasminogen activators ( uPA , tPA ) and PA inhibitors ( PAI 1 , PAI 2 ) were present in ascites from both patient groups and that tPA was the predominant PA . uPA , tPA , and PAI 1 , were detected in plasma from patients and controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We examined uPA and PAI 1 as potential markers for assessing these patients and those with familial polyposis who are at risk of developing colon cancer . ^^^ We examined 77 colonic mucosa specimens taken from patients undergoing elective resection for benign and malignant colonic disease . uPA and PAI 1 were measured using a monoclonal antibody based ELISA kit ( American Diagnostica , Greenwich , CT ) and expressed as ng / mg extract protein . ^^^ Intra and interassay controls of uPA gave CV = 3 4 % and CV = 8 9 % , respectively , while those for PAI 1 were 6 7 % and 10 11 % , respectively . ^^^ The Mann Whitney test showed that both uPA and PAI 1 expression were significantly higher in colon cancer , chronic ulcerative colitis , and Crohn ' s disease than in normal colon . uPA in familial polyposis samples was similar to that of normal colon , while PAI 1 was much lower than in normal colon . ^^^ The pattern of uPA and PAI 1 expression in normal , benign and malignant colon suggests these proteins deserve further consideration as markers for assessing colon carcinoma risk . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Within 5 days , smooth muscle cells ( SMCs ) on the luminal surface expressed the mRNA for tissue type plasminogen activator ( TPA ) , urokinase type plasminogen ( UPA ) , the receptor for UPA ( UPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Quiescent endothelial cells did not express TPA , UPA , UPAR , or PAI 1 mRNA . ^^^ UPA , and UPAR , as well as PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Anti uPA monoclonal antibody ( mAb ) suppressed LPS driven TNF alpha secretion by 61 . 6 + / 5 . 9 % ( P < . 001 ) , and PAI 1 , a uPA inhibitor , suppressed it to 53 . 1 + / 8 . 2 % of the control value ( P < . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
While TPA treatment evoked a temporary increased expression of urokinase type PA ( uPA ) , the production of both types of human plasminogen activator inhibitors ( PAI ) was induced and sustained over 12 h by TPA treatment shifting the protease protease inhibitors balance in favor of the inhibitors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
It was found that urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and plasminogen activator inhibitor type 1 ( PAI 1 ) were expressed diffusely in most thyroid carcinomas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TGF beta 1 increases fibronectin expression and urokinase plasminogen activator ( uPA ) activity and plasminogen activator inhibitor 1 ( PAI 1 ) levels in 3D cultures . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The cellular distribution of mRNAS for urokinase type plasminogen activator ( uPA ) , its specific receptor ( uPAR ) , and its inhibitors ( PAI 1 and 2 ) in mouse skin was analyzed by in situ hybridization after topical application of the tumor promoter phorbol 12 myristate 13 acetate . ^^^ In the epidermis , strong signals for uPA and PAI 1 mRNA were detected 24 h after treatment in the basal and suprabasal epidermal keratinocytes in areas with pronounced hyperproliferation and increased terminal differentiation , and in some hair follicle keratinocytes . ^^^ In the dermis , 5 h after application of phorbol 12 myristate 13 acetate to the skin , uPA mRNA was detected in fibroblast like cells below and around the skin muscle , and PAI 1 mRNA was detected in stromal cells located above the skin muscle . ^^^ Up to 24 h after the application of phorbol 12 myristate 13 acetate , the intensity of the signal for both uPA and PAI 1 increased , followed by a gradual decrease for up to 7 days . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrin gel degradation occurred through plasmin mediated fibrinolysis , which was initiated by fibroblasts exhibited high uPA but low plasminogen activator inhibitor 1 ( PAI 1 ) activities , and transforming growth factor beta 1 prevented fibrinolysis of normal fibroblasts by upregulating PAI 1 while downregulating uPA activities . ^^^ In contrast , keloid fibroblasts exhibited an intrinsically high level of PAI 1 and a low level of uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , single deficient mice lacking tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , or PA inhibitor type 1 ( PAI 1 ) gene function were recently found to have normal reproduction , although mice with a combined deficiency of tPA and uPA were significantly less fertile . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of urokinase plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and interleukin 1beta were all found to be significantly different in interfaces and in pseudocapsules , compared to controls . ^^^ PAI 1 staining was present in the neighboring areas that stained for uPA or tPA , but PAI 1 staining was also found overlapping and outside these areas . ^^^ These findings suggest a role for the uPA / uPA receptor and PAI 1 in activation and focalization of extracellular matrix degradation in periprosthetic tissues . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Prognostic relevance of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitors PAI 1 and PAI 2 in gastric cancer . ^^^ Expression of urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) was evaluated in 125 surgically resected gastric cancers by immunohistochemical analysis . ^^^ Tissue was stained immunohistochemically with a monoclonal antibody against human uPA and monoclonal antibodies against human PAI 1 and PAI 2 . ^^^ There was no significant correlation between uPA or PAI 1 expression and DNA ploidy patterns . ^^^ According to the expression of uPA and PAI 1 status , groups of 19 uPA ( ) / PAI 1 ( ) , 44 uPA ( + ) / PAI 1 ( ) , 23 uPA ( ) / PAI 1 ( + ) and 39 uPA ( + ) / PAI 1 ( + ) were subdivided . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : To evaluate the role of plasminogen activators ( tPA uPA ) and inhibitor ( PAI 1 ) in the pathogenesis of preeclampsia . ^^^ STUDY DESIGN : tPA uPA and PAI 1 antigens were measured in amniotic fluid , maternal plasma , and placental homogenates in normal pregnancy by ELISA method and compared with that of preeclampsia . ^^^ RESULTS : In normal pregnancy , tPA , uPA and PAI 1 levels increase as the gestation advance , but the increment of PAI 1 in amniotic fluid ( 28 . 3 fold ) is larger than that of tPA and uPA ( 1 . 8 fold , 8 . 5 fold ) ( p < 0 . 001 ) . ^^^ In preeclampsia , the significantly higher levels of PAI 1 were observed in AF and decidua tissue as compared to the normals ( p < 0 . 01 ) , and the increment of PAI 1 in preeclampsia is larger than that of tPA , uPA . ^^^ CONCLUSIONS : The elevated PAI 1 level is associated with the preeclampsia and the imbalance between the plasminogen activators ( tPA , uPA ) and the inhibitor ( PAI 1 ) might be involved in the pathogenesis of preeclampsia . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cysteine proteases ( cathepsin B [ CATB ] and cathepsin L [ CATL ] ) , the serine protease urokinase type plasminogen activator ( UPA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) are thought to play an important part in cancer invasion and metastasis . ^^^ The aims of this study were to measure CATB , CATL , UPA , and PAI 1 in gastric cancer ( GC ) and normal mucosa distant from the tumor ( NORM ) ; to evaluate whether tissue levels are related to tumor stage , grade , or histotype ; to assess their prognostic relevance ; and to examine UPA and PAI 1 expression immunohistochemically . ^^^ Immunohistochemistry was performed using monoclonal UPA and PAI 1 antibodies . ^^^ NORM ( CATB , CATL , UPA , PAI 1 ) tissues ; ( 2 ) in GC with versus without metastasis ( CATB , CATL , UPA ) ; ( 3 ) in poorly or moderately versus well differentiated GC ; and ( 4 ) in diffuse versus intestinal type GC ( CATB , CATL ) . ^^^ Cancer and stromal cells , showed immunoreactivity to anti UPA and anti PAI 1 antibodies . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activation was assessed by measuring the plasmin activity and plasminogen activator inhibitor 1 ( PAI 1 ) levels in cell conditioned media and the cell associated urokinase type plasminogen activator ( uPA ) levels . ^^^ Treatment of MDA MB 231 breast carcinoma cells with either thrombospondin or TGF beta 1 caused increased secretion of PAI 1 with a concomitant decrease in plasmin activity , whereas cell associated uPA expression was increased with respect to controls . ^^^ Thrombospondin and TGF beta 1 function similarly to increase cell associated uPA and cell secreted PAI 1 . ^^^ In addition , these observations suggest that thrombospondin and TGF beta 1 could promote metastasis by increasing uPA mediated cell invasion , whereas through the action of PAI 1 , also protect blood born tumor emboli from destruction by host fibrinolytic enzymes . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : A strong positive correlation exists between the breast cancer tissue content of either urokinase plasminogen activator ( uPA ) or plasminogen activator , inhibitor type 1 ( PAI 1 ) , quantified in the tissue extracts by immunoassays , and the survival of patients with breast cancer . ^^^ METHODS : The immunohistochemical localization of uPAR , uPA , tPA ) and PAI 1 was evaluated by using the avidin biotin immunoperoxidase technique and affinity purified monoclonal antibodies from American Diagnostica Inc . ^^^ CONCLUSIONS : We showed that overexpression of uPAR , uPA , and its main inhibitor , PAI 1 , is a constant feature of invasive ductal breast carcinomas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , a rapid inhibitor of both uPA and tissue type plasminogen activator ( tPA ) is the major physiologic regulator of plasminogen activator activity . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) , a rapid inhibitor of both uPA and tissue type plasminogen activator ( tPA ) is the major physiologic regulator of plasminogen activator activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : In pregnant women with HELLP syndrome ( n = 18 ) , pre / eclampsia ( n = 21 ) and highly pathological Doppler flow measurements ( hpD ) ( n = 13 ) , plasma and placental tissue extract concentrations of uPA , uPA receptor , tPA , PAI 1 , MMP 8 , MMP 9 , TIMP 1 , thrombomodulin , and angiogenin were measured using ELISA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MDA MB 231 BAG cells were found to express high protein levels of uPA , uPAR and PAI 1 . ^^^ MDA MB 435 BAG cells produced low amounts of uPA , PAI 1 and moderate amounts of uPAR , whereas MCF 7 BAG cells showed low levels of uPA , uPAR and PAI 1 protein . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This analysis of an athymic mouse model of prostate carcinoma further defines the role of the uPA / PAI 1 / plasmin system in primary growth and metastasis . ^^^ Expression of PAI 1 by malignant prostate cells resulted in a less aggressive phenotype , presumably by inhibition of uPA activity , suggesting pharmacologic or molecular inhibition of uPA activity as a potential therapeutic target . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In breast cancer , receptor bound urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 seem to play an important role in the dissolution of the surrounding tissue and the formation of tumour stroma . ^^^ The study of ' classical ' and ' new ' prognostic factors showed that uPA and PAI 1 content of breast cancer tissue are strong and independent prognostic factors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen and plasmin system , which is mainly regulated by urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and its inhibitor ( PAI 1 ) , is generally believed to play a role in cancer invasion and metastasis . ^^^ This study was conducted to investigate the role of uPA , uPAR and PAI 1 in the invasion and metastasis of gastric adenocarcinoma . ^^^ The expression of mRNAs for uPA and PAI 1 was determined by Northern blot analysis in nine primary gastric cancer tissues , nine paired metastatic lymph nodes and normal gastric mucosa . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Northern blot analyses of RNA from the cultured cells demonstrated that the steady state levels of mRNA for uPA , but not for tPA and plasminogen activator inhibitor 1 , were decreased by indomethacin ; this decrease was reversed by prostaglandin E 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In line with this hypothesis , we have studied , by immunohistochemistry , the distribution of PAI 2 , uPA and tPA in the normal and in the lesional epidermis of patients with lupus erythematosus ( LE ) , a disease in which epidermal differentiation is disturbed . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : Concentrations of all antigens ( uPA , tissue type PA ( tPA ) , uPAR , and PAI 1 ) , were significantly greater in RA than OA ; those in OA were significantly greater than normal . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These data suggest that rat Sertoli cells , similar to ovarian granulosa cells , are capable of secreting both tPA and uPA , as well as PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS AND RESULTS : When human cerebral microvascular endothelial cells ( HCMEC ) , pial arterial endothelial cells , and middle meningeal arterial endothelial cells were exposed to 10 to 1000 ng / mL recombinant tissue type plasminogen activator ( RTPA ) , urokinase type plasminogen activator ( UPA ) , or streptokinase / plasminogen ( 37 U streptokinase plus 2 mumol / L plasminogen ) for 24 hours , they exhibited concentration dependent decreases in elaboration of PAI 1 of 65 + / 3 % , 48 + / 3 % , and 59 + / 8 % . ^^^ UPA and streptokinase / plasminogen elicited decreases of 33 + / 8 % and 35 + / 4 % , respectively , that were specific with respect to the protease agonists as to total protein synthesis and cell type ; ie , neither human umbilical vein endothelial cells nor cerebral pericytes exhibited inhibition of PAI 1 elaboration . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : A marked increase in the expression of tissue factor ( TF ) and type 1 plasminogen activator inhibitor ( PAI 1 ) and an inhibition of tissue type and urokinase type plasminogen activators ( tPA and uPA , respectively ) , matrix metalloproteinases ( MMP ) , and endothelin 1 ( ET 1 ) expression accompany progestin induced decidualization of estrogen primed endometrial stromal cells both in vivo and in vitro . ^^^ Conversely , progesterone withdrawal reduces TF and PAI 1 expression and increases tPA , uPA , MMP , and ET 1 expression accounting for the hemorrhage , enhanced fibrinolysis , ECM degradation , and ischemic spiral arterial vascular injury characterizing menstruation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activator ( PA ) / plasmin system has been extensively investigated in these processes , and descriptive studies have demonstrated that urokinase type PA ( uPA ) , uPA receptor ( uPAR ) and PA inhibitor 1 ( PAI 1 ) are expressed by endothelial cells during angiogenesis in vivo . ^^^ These findings are discussed in the context of recent observations on uPA , uPAR , PAI 1 and plaminogen deficient mice , in which developmental and physiological angiogenesis appear to occur normally . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Embryo implantation in mouse : fetomaternal coordination in the pattern of expression of uPA , uPAR , PAI 1 and alpha 2MR / LRP genes . ^^^ The sites of synthesis of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and alpha 2 macroglobulin receptor / low density lipoprotein receptor related protein ( alpha 2MR / LRP ) transcripts were determined by in situ hybridization . ^^^ High levels of uPA mRNA were found in invasive trophoblast cells , while the same cells did not appear to synthesize PAI 1 . ^^^ Immunohistochemistry with uPA and PAI 1 antibodies revealed areas of co localization of these secreted proteins with the expression domains of uPAR and alpha 2MR / LRP , which is of great interest in view of the role of these two receptors in clearing uPA PAI 1 complexes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is an important regulator of plasminogen activation , which inhibits both tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is an important regulator of plasminogen activation , which inhibits both tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumour necrosis factor alpha ( TNF alpha ) and interleukin 1 beta ( IL 1 beta ) increased in several , but not all , cell lines the production of urokinase type plasminogen activator ( uPA ) , tissue type PA ( tPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) as analysed by zymography , enzyme immunoassays and Northern analysis . ^^^ For example , there was a dose dependent up regulation of uPA and PAI 1 in SW 620 cells , whereas increased uPA production in SW 1116 cells was not accompanied by an increase in PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The clinical significance of secreted levels of uPA , its receptor ( uPAR ) , and its inhibitors ( PAI 1 and PAI 2 ) in the ascites of patients with epithelial ovarian cancer patients was investigated . ^^^ METHODS : uPA , uPAR , PAI 1 , and PAI 2 were measured in the primary ascites of 36 patients with epithelial ovarian cancer by enzyme linked immunosorbent assay , and normalized to protein content . ^^^ Therefore , secreted uPAR and PAI 1 may modulate uPA activity and lead to improved outcome . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Finally , we show that uPA can rapidly reverse this effect of PAI 1 . ^^^ Taken together , these results suggest a dynamic regulatory role for PAI 1 and uPA in uPAR mediated cell adhesion and release . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This review focuses on the main components of the fibrinolytic system tissue plasminogen activator ( tPA ) , urokinase ( uPA ) and plasminogen activator inhibitor ( PAI 1 ) and on thrombin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In a prospective series of 203 resected patients , the expression of immunohistochemically assessed uPA , uPA receptors and PAI 1 was strongly associated with survival . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : It has been proposed that the serine protease urokinase type plasminogen activator ( UPA ) and its inhibitor type 1 ( PAI 1 ) may play an important part in cancer spread and metastasis . ^^^ To determine the UPA , PAI 1 antigen levels in gastric cancer ( GC ) and in normal gastric mucosa far from the tumor ( NORM ) . 2 . ^^^ RESULTS : Significantly higher UPA and PAI 1 antigen levels were found : 1 . in GC vs . ^^^ CONCLUSION : Our results confirm that the serine protease UPA and its inhibitor PAI 1 play an important role in GC progression . ^^^ Considering the higher protease levels detected in GC with metastases and poorer differentiation , UPA and PAI 1 might be useful for identifying gastric cancer patients with a poor prognosis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study we investigated the correlation of the Plasminogen Activator Inhibitor 1 ( PAI 1 ) , which is the specific inhibitor of uPA and which seems to be important for tumour formation , with prognosis in breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In 155 patients with primary breast cancer levels from PAI 1 and uPA were measured in cytosol with monoclonal antibodies and by an enzyme linked immunosorbent assay . 35 tumour tissue samples form benign breast were also examined . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Using mice with inactivated tissue PA ( tPA ) , urokinase PA ( uPA ) , or type 1 PA inhibitor ( PAI 1 ) genes , we evaluated whether these processes , or their stimulation by parathyroid hormone ( PTH ) or 1 , 25 dihydroxyvitamin ( 1 , 25 [ OH ] 2D3 ) are dependent on these genes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The stimulatory effect was not specific for UPA , in that tissue type PA ( TPA ) also increased migration ( 169 + / 9 % of control , 10 nmol / L , P < . 001 ) ; the augmentation was inhibited by pretreatment with DFP , PAI 1 , or aprotinin and was additive to the UPA effect . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The present study was undertaken to determine whether uPA and plasminogen activator inhibitor 1 ( PAI 1 ) mRNAs are expressed in vivo in the decidua of pregnant rats and in the deciduoma of `` pseudopregnant ' ' rats . ^^^ Total RNA was prepared from nondecidualized and decidualized endometrial tissues at various stages of early pregnancy and examined by Northern blot analysis using specific cDNA probes for rat uPA and PAI 1 . ^^^ There was a gradual increase in PAI 1 mRNA in the decidua from Day 7 of pregnancy , reaching a peak level on Day 15 when the decidua was transformed into the maternal placenta . ( RNA was not analyzed beyond Day 15 of pregnancy in this study . ) In situ hybridization studies verified that uPA mRNA was present in the decidua adjacent to the implanting embryo on Day 7 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition , the different uPA ELISA kits use antibodies which differ in specificity and affinity for the various forms of uPA including pro uPA , HMW uPA , LMW uPA , the aminoterminal fragment ( ATF ) and complexes with inhibitors ( PAI 1 and PAI 2 ) and the receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition to that we compared the uPA R mRNA levels with uPA R , uPA , and PAI 1 protein levels in culture supernatants and cell lysates . ^^^ The obtained results in breast cancer cell lines with different invasiveness and in benign epithelial cell lines revealed the complex cooperation of the urokinase type proteolytic pathway . uPA , uPA R , and PAI 1 are to be considered as a diagnostic tool rather than assaying a particular molecule alone . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : Urokinase type plasminogen activator ( uPA ) , uPA receptor , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , matrix metalloproteinases MMP 8 , MMP 9 and tissue inhibitor of metalloproteinases TIMP 1 were measured by ELISA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Accordingly , PAI 1 was recovered in a reactive centre cleaved form from incubations with urokinase type plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) at 0 degree C , but not at 37 degrees C . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Since TNF alpha may contribute to thrombotic complications in sepsis patients , we determined markers of thrombin activation , parameters of the fibrinolytic system ( D dimer , tissue plasminogen activator antigen ( tPA ) urinary type plasminogen activator antigen ( uPA ) , plasminogen activator inhibitor antigen ( PAI 1 ) and von Willebrand factor antigen ( vWF ) in 30 patients with sepsis or septic shock . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) generates plasmin , a process inhibited by plasminogen activator inhibitor ( PAI ) 1 and localized to the cell surface by binding of uPA to a specific receptor . ^^^ Northern analysis showed cellular expression of messenger RNA ( mRNA ) for PAI 1 , uPA , and uPA receptor . ^^^ Zymography / reverse zymography identified cell surface associated uPA activity and uPA and PAI 1 in culture media . ^^^ Net uPA activity in culture media was maximal after 7 days in culture and then declined , whereas PAI 1 antigen levels remained consistently elevated between 7 and 21 days in culture . ^^^ Treatment of cultured HSCs with retinoic acid ( 1 micromol / L ) increased uPA secretion 2 . 6 fold but did not alter PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The activities , antigens and messenger RNA ( mRNA ) levels of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) in articular cartilage were measured in patients with no history of joint diseases ( control ) , those with osteoarthritis ( OA ) classified into osteophyte formed site ( OS ) and weight bearing site ( WS ) , and in patients with rheumatoid arthritis ( RA ) . 2 . ^^^ Weight bearing site patients expressed a high uPA mRNA level but a low PAI 1 mRNA level . ^^^ Osteophyte formed site patients expressed a low uPA mRNA level but a high PAI 1 mRNA level . 3 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : The plasminogen system , which includes tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , and their main inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) , plays a major role in both fibrinolysis and tissue remodeling . ^^^ This study compares the levels of tPA , uPA , and PAI 1 at the groin and ankle in normal and varicose greater saphenous vein ( GSV ) . ^^^ Assays of the supernatants were obtained for tPA , uPA , and PAI 1 protein by enzyme linked immunosorbent assay . ^^^ In contrast , inhibitor supernatants were significantly lower for uPA and PAI 1 than control supernatants ( p < 0 . 05 ) , suggesting that uPA and PAI 1 were actively synthesized . ^^^ CONCLUSIONS : In the tissue explant supernatant model uPA and PAI 1 are actively synthesized , but tPA is not . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of matrix metalloproteinase 1 ( MMP 1 ) , matrix metalloproteinase 8 ( MMP 8 ) , matrix metalloproteinase 9 ( MMP 9 ) , lactoferrin and urokinase plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) and the inhibitors , tissue inhibitor of metalloproteinase 1 ( TIMP 1 ) , plasminogen activator inhibitor 1 ( PAI 1 ) , plasminogen activator inhibitor ( PAI 2 ) , and alpha 2 macroglobulin in the synovial fluids of patients with rheumatoid arthritis was determined before and during chemical synoviorthesis with a sodium salt of the fatty acids from cod liver oil ( Varicocid ) . ^^^ The proteases , MMP 8 , MMP 9 and uPA were increased 8 h after the treatment , whereas the specific inhibitors TIMP 1 , PAI 1 and PAI 2 showed significant changes only 24 h after the injection . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To clarify the specific expression and regulation of mRNAs for urokinase ( uPA ) , its receptor ( uPAR ) , and type 1 plasminogen activator inhibitor ( PAI 1 ) , 1 analyzed RNA from four human cancer cell lines by RNA blotting after treatment with cycloheximide , anisomycin , emetine or puromycin . ^^^ Different time patterns of induction for uPA , uPAR and PAI 1 mRNA suggest that even in the same cell type , inhibitors of protein synthesis mediate their effects on various genes through different mechanisms . ^^^ Thus , induction of uPA , uPAR , and PAI 1 transcripts by inhibitors of protein synthesis was dependent on the gene , the cell line , and the type of inhibitor , and inhibition of protein synthesis per se was not sufficient for induction of these transcripts . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The incubation of mesangial cells with TSP increased the secretion of tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) , while plasminogen activator inhibitor type 1 ( PAI 1 ) decreased . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) were administered to determine the effect of TGF beta activation on the axial length in normal and FDM eyes . ^^^ In the nondeprived eyes , the vitreous chamber depth and axial length were reduced after uPA treatment , whereas PAI 1 increased them . ^^^ In the form deprived eyes , uPA inhibited vitreous depth and axial length elongation , but PAI 1 had no effect . ^^^ The uPA and PAI 1 treatment controls the activation of TGF beta and affects axial length . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In order to clarify a role of stromal cells in sex steroidal neovascularization , plasminogen activator inhibitor ( PAI ) 1 [ an inhibitor of tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) ] and its messenger ribonucleic acid ( mRNA ) were analysed in fibroblasts derived from uterine endometrium as a model for endometrial stromal cells under the influence of sex steroids . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of uPA , its inhibitors PAI 1 and PAI 2 , and the uPA receptor ( uPAR ) have prognostic value in breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Many lines of evidence support an involvement of urokinase plasminogen activator ( uPA ) and its type 1 inhibitor ( PAI 1 ) in the migration of a variety of cells , including normal keratinocytes and carcinoma lines . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This study demonstrated the profile of the neutral proteinases , 1 ) matrix metalloproteinases ( MMP ) 1 , 2 , 3 , and 9 , and 2 ) serine proteinases , elastase , cathepsin G , urokinase and tissue type plasminogen activators ( uPA and tPA ) as well as their inhibitors , namely , tissue inhibitor of matrix metalloproteinases ( TIMP ) 1 , alpha 1 antitrypsin , alpha 1 antichymotrypsin , plasminogen activator inhibitor ( PAI ) 1 & 2 , around loose hip prostheses to clarify the step in the cascade of biological host response in the loosening of replaced total hip joints . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activator system ( PA system ) consists of urokinase type plasminogen activator ( uPA ) , tissue type PA ( tPA ) , as well as the two types of plasminogen activator inhibitors ( PAI 1 and PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 in benign , borderline , malignant primary and metastatic ovarian tumors . ^^^ Elevated levels of expression of the urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 have shown to be related to poor prognosis in a variety of cancer types . ^^^ In the present study , cytosolic levels of uPA and PAI 1 were determined with enzyme linked immunosorbent assays in cytosols prepared from 244 human ovarian tissues of different histological sub types . ^^^ Both uPA and PAI 1 were significantly associated with the malignant progression of ovarian tissues ; the levels were increased going from normal tissue , via benign and borderline adenomas , to primary and metastatic adenocarcinomas . ^^^ For the 90 patients ( 34 early stage and 56 patients with advanced disease ) from whom the primary adenocarcinoma tissues were examined , uPA and PAI 1 levels were evaluated for their association with clinicopathological parameters and with progression free and overall survival . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Available plasmin , required for MMP zymogen activation , is regulated by plasminogen activators ( uPA , tPA ) and plasminogen activator inhibitors ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Invasion is an active process and correlations are observed between cellular invasivness and proteinase production , like uPA , tPA and its inhibitors , for example PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : Cysteine proteases [ cathepsin B ( CATB ) , cathepsin L ( CATL ) ] , the serine protease urokinase type plasminogen activator ( UPA ) and its inhibitor type 1 ( PAI 1 ) play an important part in cancer invasion . ^^^ AIMS : To determine CATB , CATL , UPA , PAI 1 in chronic atrophic gastritis , intestinal metaplasia and gastric epithelial dysplasia , as precancerous changes , and to compare these data with those obtained in gastric cancer . ^^^ RESULTS : CATB , CATL , UPA and PAI 1 were significantly higher in chronic atrophic gastritis than in controls ( CATB : P < 0 . 001 ; CATL : P < 0 . 005 ; UPA : P < 0 . 000001 ; PAI 1 : P < 0 . 005 ) . ^^^ CONCLUSIONS : Our study demonstrates that cathepsins , UPA and PAI 1 may have a role not only in the process of cancer invasion , but also in the progression of precancerous changes into cancer . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To know the effects of sex steroids on the potentials of growth , invasion , and metastasis with neovascularization of endometrial cancer , the expression of plasminogen activator inhibitor ( PAI ) 1 [ an inhibitor of tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) ] and its mRNA in well differentiated uterine endometrial cancer cell line Ishikawa was determined by an enzyme linked immunosorbent assay and reverse transcription polymerase chain reaction Southern blotting ( RT PCR SB ) , respectively , under the influence of sex steroids . ^^^ Therefore , sex steroidal induction of PAI 1 might contribute to the inhibition of invasion and metastasis , concomitantly with the inhibition of neovascularization associated with tPA and uPA activities , in well differentiated endometrial cancer . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The serine protease urokinase type plasminogen activator ( uPA ) and its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) , appear to have a major function in these processes . ^^^ Therefore , the authors evaluated whether the expression and activation of uPA and PAI 1 might be of clinical value as a tumor / biologically defined risk factor in patients with gastric carcinoma . ^^^ METHODS : Enzyme linked immunoadsorbent assays were used to test for uPA antigens and PAI 1 in tissue extracts of normal and cancerous tissue from 160 gastric carcinoma patients who were enrolled in the Yonsei Cancer Center Study Group . ^^^ RESULTS : Both uPA and PAI 1 levels were significantly higher in cancerous tissues than in normal tissues ( uPA : 9 . 4 + / 8 . 7 vs . 5 . 3 + / 3 . 1 ng / mg protein cytosol ; PAI 1 : 10 . 9 + / 9 . 1 vs . 5 . 8 + / 2 . 9 ng / mg protein cytosol ) , ( P < 0 . 001 , respectively ) . ^^^ Both high uPA and PAI 1 levels were associated with differentiation of the tumor ( P = 0 . 04 and P = 0 . 004 , respectively ) , and a high PAI 1 level was associated with lymph node metastasis at an advanced stage ( P = 0 . 003 and P = 0 . 04 , respectively ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immortalized first trimester human cytotrophoblasts ( HTR 8 / SVneo ) were cultured in the absence or presence of TGF beta 1 ( 0 10 ng / ml ) for 24 h , after which the levels of urokinase type PA ( uPA ) , PAI 1 and uPA activity in the serum free conditioned media were determined by enzyme linked immunosorbent assay ( ELISA ) , protein zymography , and a chromogenic uPA activity assay . ^^^ Thus , it appears that the reduced uPA activity observed in the cultures incubated with TGF beta 1 is due to reduced secretion of uPA and increased PAI 1 production and secretion . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , plasminogen activator inhibitor 1 ( PAI 1 ) can stimulate melanoma cell migration on VN , presumably by inhibiting uPA / uPAR mediated cell adhesion to VN and thereby releasing the inhibition of cell migration induced by uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Thus , we studied the role of APC on fibrinolysis in placenta . ( 1 ) uPA activity of cell membrane reappears after incubation with uPA / PAI 1 complex and a large amount of APC by flow cytometry , ( 2 ) APC was made PAI 1 / APC complex after incubation of uPA / PAI 1 complex with APC . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In mice lacking either tissue type PA ( tPA ) or PA inhibitor type 1 ( PAI 1 ) the plasmin activity levels prior to ovulation were similar to wild type mice , while extracts prepared from urokinase type PA ( uPA ) deficient mice had 10 % or less of the plasmin activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To determine whether the T cell lymphokines interleukin 4 ( IL 4 ) and interferon gamma ( IFN gamma ) modulate SMC fibrinolysis and migration induced by basic fibroblast growth factor ( bFGF ) , we examined the effects of IL 4 and IFN gamma on human SMC tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( UPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) antigen production , determined by enzyme linked immunosorbent assays . ^^^ Although IL 4 had no effects on SMC tPA , UPA , and PAI 1 production , it potentiated bFGF induced tPA , UPA , and PAI 1 antigens . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The function of uPA at this stage was tested using the protease inhibitors aprotinin , alpha 2 antiplasmin , or plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Prognostic significance of PAI 1 and uPA in cytosolic extracts obtained from node positive breast cancer patients . ^^^ The different components of this system . e . g . urokinase plasminogen activator ( uPA ) , its receptor uPAR , as well as its main inhibitor plasminogen activator inhibitor type 1 ( PAI 1 ) have all been shown to have prognostic value in breast cancer , i . e . high tumor levels are associated with a poor prognosis . ^^^ In order to further substantiate the prognostic value of uPA and PAI 1 , we have tested the cutpoints ( median values and optimized outpoints ) from our first study ( Cancer Res 53 : 2513 2521 , 1993 ) in an independent group of breast cancer patients . ^^^ Nearly identical results were obtained when using the optimized PAI 1 or uPA value . ^^^ In a Cox multivariate analysis which included other established prognostic factors , high PAI 1 was found to be an independent prognostic variable predicting short overall survival with a relative risk of 2 . 27 in postmenopausal women , and high uPA was found to be an independent prognostic variable predicting short recurrence free survival with a relative risk of 1 . 86 in postmenopausal women . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
CONCLUSIONS : Tat affects the fibrinolytic activity of tumour cell lines derived from BKV / tat transgenic mice by modulating the production of both uPA and PAI 1 via autocrine and paracrine mechanisms of action . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Similarly , there was no association between CSF PAI 1 concentrations and urokinase type plasminogen activator ( uPA ) . ^^^ Moreover , PAI 1 may play an important role in regulating the functions tPA , and probably uPA , in CSF . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Evidence of a non conventional role for the urokinase tripartite complex ( uPAR / uPA / PAI 1 ) in myogenic cell fusion . ^^^ Incubation of cultures with either uPA anticatalytic antibodies , or the amino terminal fragment of uPA ( ATF ) , which inhibits competitively uPA binding to its receptor , or anti PAI 1 antibodies , which inhibit uPA binding to PAI 1 , resulted in a 30 to 47 % decrease in fusion . ^^^ Decreased fusion rates induced by interfering with uPAR / uPA / PAI 1 interactions were not associated with significant changes in mRNA levels of both the myogenic regulatory factor myogenin and its inhibitor of DNA binding , Id . ^^^ Incubation of cultures with purified uPA resulted in a decrease in fusion , likely due to a competitive inhibition of PAI 1 binding of endogenous uPA . ^^^ We conclude that muscle cell fusion largely depends on interactions between the members of the urokinase complex ( uPAR / uPA / PAI 1 ) , but does not require proteolytic activation of plasmin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These data indicate that PAI 1 plays a direct role in dynamic cell adhesion particularly at the leading edge , where increased levels of urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) are localized in migrating cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A sensitive and robust assay for urokinase and tissue type plasminogen activators ( uPA and tPA ) and their inhibitor type 1 ( PAI 1 ) in breast tumor cytosols . uPA and PAI 1 are becoming established as amongst the most effective markers of poor prognosis for patients with node negative breast cancer ; tPA is an index of longer survival . ^^^ This paper describes a sensitive ELISA for the measurement of uPA , tPA and PAI 1 in breast cancer cytosols . ^^^ It is the first published assay to yield strictly comparative values for uPA , tPA and PAI 1 in tissue extracts and is readily subject to external quality control . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Levels of uPA , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) were measured semiquantitatively in paraffin sections of tumours from 147 patients with NSCLC . ^^^ There was a significant positive relationship between PAI 1 levels and T stage ( p = < 0 . 05 ) in the total group , and survival status ( p = < 0 . 05 ) in the SCC subgroup alone . uPA and uPAR levels were not significantly associated with tumour staging or survival . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recycling was directly demonstrated in cell surface biotinylated , uPA : PAI 1 exposed cells in which biotinylated uPAR was first internalized and subsequently recycled back to the surface upon incubation at 37 degrees C . ^^^ In fact , uPAR was resistant to PI PLC after the 4 degrees C binding of uPA : PAI 1 to biotinylated cells , but upon incubation at 37 degrees C PI PLC sensitive biotinylated uPAR reappeared at the cell surface . ^^^ Binding of uPA : PAI 1 by uPAR , while essential to initiate the whole process , was , however , dispensable at later stages as both internalization and recycling of uPAR could be observed also after dissociation of the bound ligand from the cell surface . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Mutational analysis of the genes encoding urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 in advanced ovarian cancer . ^^^ Evidence has accumulated that urokinase type plasminogen activator ( uPA ) , its inhibitor ( PAI 1 ) and receptor ( uPAR ) are involved in tumor invasion and metastasis . ^^^ In order to elucidate the possible role of the Pro121Leu exchange in uPA and the Ala / Thr variants in the signal sequence of PAI 1 in the development and / or progression of human ovarian cancer , we studied the presence of these mutants or variants in a series of 22 ovarian cancer tissues . ^^^ Taken together , these results suggest that the polymorphisms observed in the uPA and PAI 1 genes may not be linked to ovarian cancer . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In particular , integrin dependent cell contact , spreading and ( trans ) migration can be modulated by ECM associated PAI 1 and uPA receptor driven reactions that are intimately linked to the invasive potential of cells . ^^^ Recently , mechanisms of molecular crosstalk between these receptor systems have been recognized : ( a ) uPA receptor may directly interact with beta 1 and beta 2 integrins on circulating blood cells ; ( b ) av beta 3 integrin directly binds to a matrix metalloproteinase ; ( c ) uPA and PAI 1 balance the high affinity binding of vitronectin to uPA receptor ; ( d ) vitronectin dependent cell adhesion and migration involving alpha 5 integrins or uPA receptor are blocked by active PAI 1 independent of its role as protease inhibitor . ^^^ These results are compatible with vascular injury studies in uPA and PAI 1 knock out mice and provide new targets for the treatment of diseases associated with imbalanced vascular remodelling . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Strong clinical and experimental evidence has accumulated that the tumor associated serine protease plasmin , its activator uPA ( urokinase type plasminogen activator ) , the receptor uPA R ( CD 87 ) , and the inhibitors PAI 1 and PAI 2 are linked to cancer invasion and metastasis . ^^^ In cancer , increase of uPA , uPA R , and / or PAI 1 is associated with tumor progression and with shortened disease free and / or overall survival in patients afflicted with malignant solid tumors . uPA and / or its inhibitor PAI 1 appear to be one of the strongest prognostic markers so far described . ^^^ Due to the strong correlation between elevated uPA and / or PAI 1 values in primary cancer tissues and the tumor invasion / metastasis capacity of cancer cells , proteolytic factors have been selected as targets for therapy . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Although tissue type plasminogen activator ( tPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) are believed to be involved in the biochemical cascade leading to extracellular matrix degradation during ovulation , the presence and possible role of urokinase type PA ( uPA ) and its receptor ( uPAR ) in follicular wall remodeling during follicular development are poorly understood . ^^^ In the current studies , we have examined their presence in the rat ovary and compared the changes in both uPA and uPAR expression with those of tPA and PAI 1 during follicular growth in vivo . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( UPA ) and its inhibitor PAI 1 are thought to play an important part in gastric cancer ( GC ) invasion and metastasis . ^^^ The aims of the present study were : ( 1 ) to measure UPAR , UPA and PAI 1 levels in GC and in non malignant tissue distant from the tumor ( NORM ) ; ( 2 ) to evaluate their relationship with histomorphological parameters ; and ( 3 ) to determine their prognostic value . ^^^ UPAR , UPA and PAI 1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery . ^^^ UPAR , UPA and PAI 1 were significantly higher in GC vs NORM , in the presence of metastasis ( UPAR , UPA ) and in undifferentiated GC ( UPAR , PAI 1 ) . ^^^ UPAR significantly correlated with UPA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here , we tested whether the systemic treatment of mice with kainic acid ( KA ) , an amino acid inducing limbic seizures , could elevate in the brain mRNAs encoding uPA and its specific inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) , a major antifibrinolytic agent . ^^^ Here , both mRNAs were initially elevated in the hilar region of the dentate gyrus and in the molecular and oriens layers ; however , PAI 1 mRNA became evident throughout the area , while uPA mRNA became especially pronounced in the CA3 / CA4 subfield . ^^^ In the amygdaloid complex , uPA mRNA was restricted to the basolateral nucleus , whereas PAI 1 mRNA was seen throughout the structure , however , excluding this nucleus . ^^^ These data show that seizure activity enhances the expression of uPA and PAI 1 genes in the brain ; the patterns of enhancement suggest that the protease and its inhibitor may act in brain plasticity in synchrony , however , also independently of each other . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 mRNA was localized mainly in germ cells except late spermatids . uPA mRNA was expressed stage specifically in Sertoli cells of adult testis . uPA receptor mRNA was localized in germ cells of mature testis but not in spermatogonia or late spermatids . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In 15 patients we investigated coagulation parameters before , during and post CPB , i . e . , fibrinogen , antithrombin ( AT ) 3 , thrombin antithrombin complex ( TAT ) , prothrombin fragments F 1 + 2 ( F 1 + 2 ) , factor ( F ) XIIa , tissue factor ( TF ) , and parameters of the fibrinolytic system , i . e . , plasmin antiplasmin complex ( PAP ) , D dimer , tissue plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Time varying prognostic impact of tumour biological factors urokinase ( uPA ) , PAI 1 and steroid hormone receptor status in primary breast cancer . ^^^ In breast cancer , several investigations have demonstrated that the tumour biological factors uPA urokinase type plasminogen activator ) and its inhibitor PAI 1 are statistically independent , strong prognostic factors for disease free ( DFS ) and overall survival ( OS ) . ^^^ We therefore investigated the time dependent prognostic power of uPA , PAI 1 and steroid hormone receptor status applying the time varying coefficient model of Gray . uPA and PAI 1 were analysed by enzyme linked immunosorbent assay in tumour tissue extracts from 314 breast cancer patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumor associated proteolytic factors uPA and PAI 1 in endometrial carcinoma . ^^^ The levels of plasminogen activator urokinase ( uPA ) and of its inhibitor ( PAI 1 ) were measured by use of ELISA in the cytosol of tissue homogenates obtained from endometrial carcinomas and the marginal , tumor free endometrium of postmenopausal patients ( n = 64 ) . ^^^ Significantly higher median levels of uPA and PAI 1 were found in malignant endometrium ( uPA 1 . 89 ng / mg , PAI 1 3 . 04 ng / mg ) compared to tumor free endometrium ( uPA 0 . 84 ng / mg , PAI 1 1 . 01 ng / mg ) . ^^^ Concerning uPA , no significant differences were found in dependence on histomorphological prognostic factors ( staging , grading ) , but the median level of PAI 1 was significantly higher in G2 / G3 carcinomas compared to G 1 tumors ( 5 . 08 ng / mg vs 2 . 19 ng / mg ) . ^^^ Because of the good prognosis of operated patients with endometrial carcinomas , the prognostic value of uPA and PAI 1 can only be decided by a larger number of patients and a long observation time . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVES : To evaluate the effect of therapeutic and pharmacologic concentrations of two non steroidal anti inflammatory drugs ( NSAIDs ) , nimesulide and naproxen , on the synthesis of urokinase ( uPA ) , plasminogen activator inhibitor ( PAI 1 ) and interleukin 6 ( IL 6 ) in human synovial fibroblasts isolated from osteoarthritis ( OA ) patients . ^^^ The suppressive action of the two drugs on the synthesis of uPA , while stimulating PAI 1 production , may have a positive impact on the balance of plasminogen activator / inhibitor , which could help reduce cartilage catabolism . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
There is no information available on the relation between response to chemotherapy and the high risk phenotype assessed by uPA and / or PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Using Northern blot analysis , in situ hybridization , and immunohistochemistry , the expression of uPA , its receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and transforming growth factor beta 1 ( TGF beta 1 ) was studied in 14 patients undergoing pancreatic resection for CP . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the primary cancers , PAI 2 levels correlated weakly but significantly with those of uPA and PAI 1 , but not with tissue type plasminogen activator ( tPA ) or uPA receptor ( uPAR ) levels . ^^^ In contrast to findings at the protein level , PAI 2 mRNA levels failed to correlate with those for uPA or PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In 587 frozen samples of malignant and nonmalignant tissue of breast , uterus , vulva , and ovary , levels of urokinase plasminogen activator ( uPA ) , tissue plasminogen activator ( tPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) were examined with enzyme linked immunosorbent assay ( ELISA ) and cathepsin D ( cath D ) with radioimmunoassay . ^^^ UPA , PAI 1 and cath D were raised in malignant tissue with significantly higher levels in breast cancer ( uPA , PAI 1 ) and ovarian cancer ( cath D ) . ^^^ In 393 primary breast cancer samples , uPA , PAI 1 , and cath D were not related to other prognostic factors , whereas tPA levels were significantly raised in prognostic more favorable carcinomas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This study characterizes the expression of tissue type plasminogen activator ( TPA ) , urokinase type plasminogen activator ( UPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) in hyperplastic vein grafts and normal venous tissue . ^^^ Strong immunohistochemical PAI 1 reactivity and in situ hybridization signals for PAI 1 and UPA mRNA were associated with the smooth muscle cells of the thickened intima of the grafts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : To compare the plasminogen activators ( tPA , uPA ) and their inhibitors ( PAI 1 , PAI 2 ) at different gestational ages , related to levels in women at term and non pregnant women . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Using in situ hybridization and immunocytochemistry , the expression patterns of uPA and PAI 1 in coronary arteries from cardiac allografts were compared to those of young individuals without disease . ^^^ RESULTS : Both PAI 1 and uPA were over expressed early after transplantation and as late as 27 months post grafting . ^^^ Of special note was the adventitial expression of uPA and PAI 1 in microvessels and myofibroblasts . ^^^ In contrast , the expression of uPA and PAI 1 in normal coronary arteries was confined to endothelial cells of the central lumen , as well as low levels of expression in intimal and medial smooth muscle cells . ^^^ CONCLUSIONS : Despite morphologic similarities between normal and transplant coronary arteries , differences were noted in the vascular expression pattern of uPA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The tissue distribution of uPA , tPA , uPA receptor ( uPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) was studied by immunohistochemistry . uPA , tPA , uPAR , and PAI 1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The molecular classification of primary breast cancer was performed by assessing the following factors : estrogen and progesterone receptors , ERbB 2 mutated p 53 , uPA , PAI 1 , VEGF , DNA Index and S Phase . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MC were found to react with antibodies against tissue type plasminogen activator ( tPA ) and urokinase receptor ( uPAR / CD87 ) , but not with antibodies against urokinase ( uPA ) or plasminogen activator inhibitors ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Enhanced invasion was not associated with significant changes in the expression of uPA or its membrane receptor UPAR ; plasminogen activator inhibitors PAI 1 and PAI 2 ; metalloproteinases MMP 1 , MMP 2 , MMP 3 , MMP 9 and membrane type MMP 1 ; or tissue inhibitors of metalloproteinases TIMP 1 and TIMP 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The complex of the type 1 plasminogen activator inhibitor ( PAI 1 ) and its target proteinases , the urokinase and tissue type plasminogen activators ( uPA and tPA ) , but not the free components , bind with high affinity to the endocytosis receptors alpha 2 macroglobulin receptor / low density lipoprotein receptor related protein ( alpha2MR / LRP ) and very low density lipoprotein receptor ( VLDLR ) . ^^^ The purified recombinant mutant proteins , rPAI 1 / R78A K124A and rPAI 1 / K82A R120A , produced by the yeast Pichia pastoris , were indistinghuisable from wild type recombinant and natural human PAI 1 with respect to inhibitory activity against uPA , stability of SDS resistant complexes with uPA , and vitronectin binding . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Our study focused on the possible roles of PAI 1 , PAI 2 , and uPA in tPA in myocyte hypertrophy and angiogenesis in the early and late stages of pressure overload induced left ventricular hypertrophy ( LVH ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Using a pregnant mare serum gonadotropin ( PMSG ) / human chorionic gonadotropin ( hCG ) induced rhesus monkey corpus luteum ( CL ) model , we have studied how urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) , are temporally expressed in CL of rhesus monkey at the luteotropic and luteolytic periods . ^^^ Slot blot analysis and in situ hybridization were performed to analyze the expression and distribution of uPA and PAI 1 messenger RNA ( mRNA ) . ^^^ The highest expression of uPA and PAI 1 mRNA was observed at the luteotropic period , while their expression decreased approximately 50 % at early luteal regression defined by considerably decreased serum progesterone levels , and remained at very low levels at the late stage of luteal regression . ^^^ We conclude that proteolysis mediated by uPA and regulated by PAI 1 may play a role in the luteal maintenance , while tPA may participate in the luteal regression in the rhesus monkey . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of uPA , activators of uPA ( cathepsin D , antithrombin 3 ) , uPA substrates ( plasminogen , matrix metalloproteinase 2 [ collagenase 4 , 72 kD ; MMP 2 ] ) , uPA / plasmin inhibitors ( plasminogen activator inhibitor type 1 and 2 [ PAI 1 , PAI 2 ] , alpha 1 antitrypsin , alpha 2 antiplasmin ) , uPA receptor ( uPA R ) , and parameters of the uPA R cycle ( alpha 2 macroglobulin , alpha 1 antichymotrypsin ) could be determined immunohistochemically and were scored semiquantitatively in 203 patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Using in situ hybridization with digoxygenin labelled cRNA probes , we have demonstrated that tPA and PAI 1 mRNAs were localized in epithelial cells of adult monkey epididymis . uPA mRNA was localized in the same areas , but to a much smaller extent . tPA , uPA and PAI 1 mRNAs were greatly expressed in the caput and corpus of adult epididymis than in other regions . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , a member of the urokinase type plasminogen activator ( uPA ) system , can already be defined as an established new prognostic factor in gastric cancer . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) , a member of the urokinase type plasminogen activator ( uPA ) system , can already be defined as an established new prognostic factor in gastric cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Invasive TCC cells selected by serial passage through a Boyden chamber demonstrated higher levels of uPA , uPA receptor and PAI 1 than parental cells ( p < 0 . 05 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In fact , in PC 3 and DU 145 cells but not in LNCaP cells , urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) are induced by bombesin treatment . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor ( PAI ) 1 and 2 , and soluble uPA receptor ( suPA R ) concentrations were assayed by enzyme linked immunosorbent assay ( ELISA ) in the conditioned media . uPA and PAI 2 concentrations were not influenced by steroid treatment and did not differ between women with and without endometriosis , whereas PAI 1 was significantly up regulated by promegestone in both groups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In HBECs , TGF beta 1 inhibited cell proliferation and uPA activity , while it augmented plasminogen activator inhibitor 1 ( PAI 1 ) antigen level . ^^^ Sodium butyrate inhibited both cell proliferation and uPA activity but did not affect the level of PAI 1 . ^^^ In MDA MB 231 , TGF beta 1 had no effect on cell proliferation but increased uPA activity and PAI 1 antigen level ; sodium butyrate inhibited both cell proliferation and uPA activity but had no effect on PAI 1 level . ^^^ Our results indicate ( 1 ) that the effects of TGF beta 1 on cell growth can be dissociated from its effects on the uPA / PAI system ; ( 2 ) that , while TGF beta 1 is a potent inhibitor of cell proliferation and uPA activity in normal cells , it may promote invasion and metastasis of tumour cells by increasing uPA activity and PAI 1 levels ; and ( 3 ) that sodium butyrate offers a potential approach to preventing tumour development by inhibiting both cell proliferation and invasion . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The authors attempted to examine the immunohistochemical expression of uPA , uPAR , and PAI 1 in patients with transitional cell carcinoma of the upper urinary tract ( TCC UUT ) . ^^^ RESULTS : There was moderate to strong cytoplasmic staining for uPA , PAI 1 , and uPAR in 57 . 8 % , 96 . 1 % , and 88 . 3 % , respectively , of tumor epithelial cells , and in 22 . 7 % , 53 . 9 % , and 24 . 7 % , respectively , of stromal cells at the tumor / stroma interface . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study we measured cathepsin D ( n=162 ) , uPA ( n=116 ) , uPAR ( n=109 ) and PAI 1 ( n=135 ) in tumor cytosols obtained from a population of node negative breast cancer patients . ^^^ A significant correlation was found between levels of uPA , uPAR , and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We suggest that this results from the action of a uPA / plasmin dependent mechanism resulting from stimulation of uPA expression , secretion and subsequent activity , despite elevated PAI 1 inhibitor levels . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of proteolytic parameters of the urokinase type plasminogen activator ( uPA ) system [ uPA receptor ( uPA R ) , plasminogen activator inhibitor ( PAI ) 1 ] has been proven to be an independent prognostic parameter in cancer . ^^^ Multivariate Cox analysis performed to correct these results for relative impact of the uPA system and established prognostic factors showed PAI 1 ( disease free survival : P=0 . 002 , relative risk 1 . 86 ; overall survival : P=0 . 005 , relative risk 1 . 39 ) , pT and pN as independent parameters . ^^^ For detailed pattern analysis , stepwise overall Kaplan Meier analyses were performed in subgroups of high uPA R , uPA , PAI 1 and cathepsin D expression for two additional proteases each . ^^^ From these analyses , the combination of high ( score 2 / 3 ) expression of uPA R , PAI 1 , antichymotrypsin and alpha 2 macroglobulin was identified as a high risk pattern , representing parameters known to be essential for uPA R internalization and recycling . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The formation of a ternary uPA / suPAR / VN complex on the cell surface and the free extracellular matrix could be inhibited by a monoclonal antibody against VN , as well as by plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have investigated the expression and cellular localization of urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator receptor ( uPAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) as well as plasminogen activation in rat liver regeneration by recruitment of progenitor ( oval ) cells . ^^^ Using a model in which surgical partial hepatectomy is combined with feeding of 2 acetylaminofluorene ( 2 AAF ) to induce liver regeneration by proliferation and differentiation of oval cells , expression of uPA , uPAR , and PAI 1 was detected by immunohistochemistry mainly in the duct like formations of expanding oval cells . ^^^ Expression of uPA , uPAR , and PAI 1 , as assessed by immunohistochemical and Northern blot analyses , was also observed , when cells located in and in close proximity to the bile epithelial structures were activated to enter DNA synthesis in response to 2 AAF , and after in vivo infusion of various growth factors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We present a systematic analysis of the sensitivity and specificity of immunohistochemical stainings for components of the plasminogen activation system , i . e . , uPA , tPA , PAI 1 , PAI 2 , and uPAR , on routinely processed ( formalin fixed , paraffin embedded ) tissues . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Whether uPA and PAI 1 are related to local recurrence , metastatic spread or both is not clear . ^^^ We present a retrospective study of 429 primary breast cancer patients with a median follow up of 5 . 1 years , in which the levels of uPA and PAI 1 in tumour extracts were analysed by means of an enzyme linked immunosorbent assay . ^^^ The median values of uPA and PAI 1 , which were used as cut off points , were 4 . 5 and 11 . 1 ng mg ( 1 ) protein respectively . ^^^ The levels of uPA and PAI 1 were correlated with tumour size , degree of anaplasia , steroid receptor status and number of positive nodes . ^^^ Patients with high content of either uPA or PAI 1 had increased risk of relapse and death . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
UPA was detected in the extracts as pro UPA , UPA complexed to plasminogen activator inhibitor 1 , or as otherwise inactive UPA antigen , but not in the active two chain form . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In situ hybridization analysis showed that the distribution and localization of mRNAs for tPA , uPA , PAI 1 and PAI 2 were similar in the fetal membranes of human and rhesus monkey ; no obvious species difference was observed . ^^^ No detectable amount of mRNAs for tPA , uPA , PAI 1 and PAI 2 was found in the fibroblast , reticular and spongy layers . ^^^ Distribution of the proteins of tPA , uPA and PAI 1 in the fetal membranes of these two species was consistent with the distribution of their mRNA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and one of its inhibitors , the PAI 1 , are involved in the proteolytic cascade of matrix degradation during in vivo morphogenesis or metastasis . ^^^ In the present study , we have characterized the in vitro morphological behavior of human normal and malignant mammary epithelial cells and determined the levels of uPA activity and PAI 1 during these events . ^^^ The epithelial cell migration correlated with an increase in the uPA activity whereas their immobility correlated with both increases in uPA activity and PAI 1 level . ^^^ In contrast , no morphological rearrangement was observed in MCF 7 cells and this correlated with both increases in uPA activity and PAI 1 level . ^^^ Altogether , these results show that the in vitro mammary epithelial behavior is under the influence of mesenchymal inductive signals and is in agreement with modifications of uPA activity and PAI 1 levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Agonist activity of antiestrogen receptor complexes to regulate urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) endogenous gene expression in breast cancer cells . ^^^ We now describe the regulation of urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) endogenous gene expression by estradiol ( E 2 ) and different antiestrogens in BC 2 cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Treatment with 12 O tetradecanoylphorbol 13 acetate ( TPA ; 100 nM ) induced the mRNAs for TIMP 1 as well as for MMP 1 , MMP 9 , the uPA receptor , and the uPA inhibitor PAI 1 , amongst which only the responses of MMP 9 and PAI 1 were cell specific . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We subjected the complex between the serine proteinase urokinase type plasminogen activator ( uPA ) and the serpin plasminogen activator inhibitor 1 ( PAI 1 ) to proteolytic digestion under nondenaturing conditions . ^^^ The complex could be degraded to a fragment containing two disulfide linked peptides from uPA , one of which included the active site Ser , while PAI 1 was left undegraded . ^^^ By further proteolytic digestion after denaturation and reduction , it was also possible to degrade the PAI 1 moiety , and we isolated a fragment containing 10 amino acids from uPA , encompassing the active site Ser , and 6 amino acids from PAI 1 , including the P 1 Arg . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Plasma tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , and the plasminogen activator inhibitors ( PAI 1 and PAI 2 ) were evaluated and compared with plasma 17 beta estradiol levels , ranging from 20 pg / mL to > 5 , 000 pg / mL during the course of treatment . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We measured the abundance and activity of urokinase plasminogen activator ( uPA ) , and the levels of PA inhibitor ( PAI 1 ) and insulin like growth factor 1 ( IGF 1 ) in conditioned media from both explants and osteoblast like cells . ^^^ RESULTS : OA explants showed increased levels and activity of uPA , no changes in PAI 1 abundance , and increases in IGF 1 release , as compared with preparations from normal individuals . ^^^ In vitro primary osteoblast like cells showed results similar to the ex vivo findings for uPA , PAI 1 , and IGF 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We also measured urokinase type PA ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) , which may not be endothelium derived but share major clearance pathways with tPA . ^^^ In M > F transsexuals , mean plasma levels of tPA ( minus 4 . 4 ng / ml ) , big ET 1 ( minus 0 . 8 pg / ml ) , uPA ( minus 0 . 5 ng / ml ) and PAI 1 ( minus 26 ng / ml ) decreased ( all Ps < or =0 . 02 ) . ^^^ In F > M transsexuals , levels of big ET 1 increased ( plus 0 . 4 pg / ml ; P = 0 . 02 ) , while tPA , uPA and PAI 1 did not change ( all Ps > 0 . 25 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Urokinase type and tissue type plasminogen activators ( uPA and tPA ) and PAI 1 were assayed in vascular SMC conditioned media and in cell lysates , using enzyme linked immunosorbent assay and western blotting . ^^^ Although the accumulation of uPA in conditioned media tended to increase also , uPA content was reduced in cell lysates ( 64 % of control with 0 . 1 mg / ml hyaluronan at 24 h ; n = 9 , P < 0 . 01 ) without any change in PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To elucidate the participation of the uPA system in the malignant behaviour of squamous cell carcinoma ( SCC ) in the oral cavity , uPA , uPAR , PAI 1 and 2 expression and localisation in 34 primary oral cancers were examined immunohistochemically . ^^^ The positive rates of uPA , uPAR , PAI 1 and 2 expression were 23 . 5 , 29 . 4 , 29 . 4 and 11 . 8 % , respectively . uPA expression correlated with mode of cancer invasion according to Yamamoto Kohama ' s criteria ( p < 0 . 01 ) and with secondary regional lymph node metastasis . uPAR expression also correlated with mode of invasion . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To understand the hormonal regulation of the components of the plasminogen plasmin system in human breast cancer , we examined the oestradiol ( E 2 ) regulation of plasminogen activators ( PAs ) , namely urokinase type plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and uPA receptor ( uPAR ) , in our model system . ^^^ Northern blot analysis showed that there was a concentration dependent down regulation of uPA , tPA and PAI 1 mRNAs by E 2 . ^^^ The E 2 also inhibited the expression and secretion of uPA , tPA and PAI 1 proteins as determined by enzyme linked immunosorbent assay ( ELISA ) in cell extracts ( CEs ) and conditioned media ( CM ) . ^^^ Thus , we now report the regulation of uPA , PAI 1 and tPA by E 2 in both mRNA and protein levels in ER transfectants . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study we analyzed the expression and distribution of the urokinase plasminogen activator ( uPA ) , its membrane receptor ( urokinase plasminogen activator receptor [ uPAR ] ) , and its inhibitor ( plasminogen activator inhibitor 1 [ PAI 1 ] ) in acute necrotizing pancreatitis in human beings . ^^^ METHODS : With immunohistochemistry and Northern blot analysis , the expression and cellular distribution of uPA , uPAR , PAI 1 , and TGF beta 1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis . ^^^ RESULTS : Northern blot analysis showed enhanced expression of uPA , uPAR , and PAI 1 in eight of 12 , seven of 12 , and nine of 12 necrotizing pancreatitis samples , respectively , compared with normal control samples . ^^^ Immunohistochemistry revealed elevated uPA , uPAR , and PAI 1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , we analyzed the expression of urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) in samples of chronically rejected human kidneys . ^^^ Immunohistochemical analysis in normal kidneys showed weak immunostaining of uPA , moderate to intense uPAR and PAI 1 immunostaining in proximal tubules , and moderate immunostaining in distal tubules , but no signal in the glomeruli or cortical vessels . ^^^ In addition , within the glomeruli of rejected kidney samples , there was positive immunostaining for uPA , uPAR , and PAI 1 in the mesangial cells , but negative staining in most of the endothelial cells , whereas the normal kidneys revealed no immunoreactivity in these structures . ^^^ CONCLUSION : The demonstrated up regulation of uPA / uPAR / PAI 1 in chronic renal rejection is consistent with the plasminogen / plasmin system contributing to tissue remodeling in this disorder . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Similar binding data and number of free binding sites , about 200 fmol / mg protein , were found for UPA in complex with its inhibitor plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^ Degradation of free UPA did not require prior binding to endogenous PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activators tPA and uPA , and their inhibitors , PAI 1 and PAI 2 , have been associated with epithelial homeostasis and wound healing . ^^^ In contrast , uPA and tPA mRNA were unchanged over the same time course . uPA , tPA , and PAI 1 mRNA increased in the presence of dbcAMP ; levels remained elevated at least 8 h . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The cultured mesothelial cells produced tissue type plasminogen activator ( t PA ) , urokinase plasminogen activator ( uPA ) , and plasminogen activator inhibitor type 1 and type 2 ( PAI 1 and PAI 2 ) during unstimulated conditions . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To determine the level of expression and the significance of urokinase type plasminogen activator ( uPA ) and its plasminogen activator inhibitor type 1 ( PAI 1 ) in adenocarcinoma of the esophagus , we studied 54 tumor cases and a control group of normal gastric mucosa cases with ELISA using detergent extracted samples . uPA and PAI 1 were significantly elevated as compared to control tissue by factors of 16 and 14 , respectively . ^^^ Median levels of both uPA and PAI 1 showed significant correlation with tumor pT , pN , and pM categories , whereas the presence of lymphatic invasion correlated only with the uPA content and tumor grade correlated only with PAI 1 content . ^^^ Using maximally selected statistics , a cutoff value was found for uPA ( 2 . 85 ng / mg protein ) but not for PAI 1 , which divided the study group into significantly poorer and better survival subgroups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
All of these cells also secreted a 100 fold greater amount of plasminogen activator inhibitor 1 than of uPA antigen , and uPA activities were not detected in the culture medium . ^^^ The secretion of uPA and plasminogen activator inhibitor 1 from HLMECs was also enhanced by tumor necrosis factor alpha and IL 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasma urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and urokinase type plasminogen activator receptor ( uPAR ) levels were measured in healthy volunteers and breast cancer patients . ^^^ In pre menopause healthy females , blood was sampled weekly during one menstruation cycle and menstruation phases ( follicular , ovulatory , luteal ) were determined by FSH / LH levels . uPA , PAI 1 , and uPAR levels were at the nadir during ovulatory phase . uPA level was highest at follicular phase while PAI 1 level was highest at luteal phase . ^^^ In comparison between pre and post menopause states , uPA and uPAR levels were higher in post menopause state while PAI 1 level was higher in pre menopause state . ^^^ In breast cancer patients , uPA , PAI 1 , and uPAR positive rates were low when we use the menopause state unmatched cut off points . ^^^ In conclusion , adjustment of physiological changes of uPA , PAI 1 , and uPAR is required in determining pathological elevation of the plasma levels in cancer patients , especially in females . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tissue extraction procedures for investigation of urokinase plasminogen activator ( uPA ) and its inhibitors PAI 1 and PAI 2 in human breast carcinomas . ^^^ Urokinase type plasminogen activator ( uPA ) and its inhibitors , plasminogen activator inhibitor type 1 ( PAI 1 ) and type 2 ( PAI 2 ) , are supposed to be involved in the expression of the invasive and metastatic phenotype of cancer cells . ^^^ One aliquot is used for cytosol preparation ; another can be treated by 2 % Triton 10 100 ( vol / vol ) and provide an extract containing the totality of uPA and PAI 1 . ^^^ Total uPA and PAI 1 are measured in a Triton extract with good performance as compared to previous investigations [ 4 ] . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Incubation with lovastatin ( 5 microM ) of proximal tubules isolated from untreated rats induced an increase in tPA and uPA and a decrease in plasminogen activator inhibitor 1 ( PAI 1 ) activities . ^^^ In vitro , supernatants , cytosols , and membranes of renal proximal tubular cells in primary cultures had no detectable uPA activity , and lovastatin ( 0 . 1 to 10 microM ) induced an increase in tPA and a decrease in PAI 1 activities and antigens . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To evaluate the relationship between tumor biological factors and the metastatic potential of primary breast cancer , proteolytic factors uPA , PAI 1 , and cathepsin L , which are associated with tumor invasion and metastasis , were determined in breast cancer tissue extracts by ELISA and the values assessed by uni and multivariate analysis as well as CART ( classification and regression trees ) in comparison with traditional prognostic factors . ^^^ Cysteine protease cathepsin L , serine protease uPA , and the protease inhibitor PAI 1 were determined by ELISA in extracts of primary tumors of 103 node negative breast cancer patients and values assessed by univariate and multivariate analysis in comparison with traditional prognostic factors ( tumor size , steroid hormone receptor status , grading , vessel invasion , menopausal status ) . ^^^ PAI 1 , cathepsin L , tumor size , grading , and steroid hormone receptor status but not uPA , vessel invasion , and menopausal status were of prognostic relevance for disease free survival ( univariate analysis ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumor biological factors uPA , PAI 1 , cathepsin D , S phase fraction ( SPF ) , MIB 1 ( Ki 67 ) , p 53 , and HER 2 / neu were assessed in 100 node negative breast cancer patients . ^^^ Antigen levels of uPA , its inhibitor PAI 1 , and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods . ^^^ Univariate analysis determined PAI 1 ( p = 0 . 0001 ) , uPA ( p = 0 . 0437 ) , MIB 1 ( p = 0 . 0214 ) , and SPF ( p = 0 . 0248 ) as statistically significant prognostic factors for DFS . ^^^ In multivariate analysis , including the statistically significant prognostic factors PAI 1 , uPA , MIB 1 , and SPF , only PAI 1 ( p = 0 . 0003 , relative risk : 4 . 7 ) proved to be of independent statistical significance for DFS . ^^^ Thus , factors describing the invasive and metastatic capacity of tumor cells ( uPA , PAI 1 ) and factors related to their proliferative activity ( SPF , MIB 1 ) provide valuable prognostic information in node negative breast cancer patients . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We measured uPA and PAI 1 activities and uPA , PAI 1 and PAI 2 antigen concentrations in cervical extracts from normal , squamous intraepithelial lesions ( SIL ) or invasive carcinoma patients . ^^^ The increase in uPA activity and the antigen levels of uPA and PAIs ( PAI 1 and PAI 2 ) in stages 2 4 of invasive carcinoma of the cervix suggests that these components play an important role in invasion and metastasis in advanced stages of this tumour . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Increased production of PAI 1 induced by 16K PRL results in the formation of inactive PAI 1 / uPA complexes , consistent with the observed decrease in uPA activity . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Northern analysis of hypoxic murine lung demonstrated an increase in PAI 1 mRNA compared with normoxic controls ; in contrast , transcripts for both tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) decreased under hypoxic conditions . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : To compare the prognostic impact of tumor angiogenesis factors ( vascular endothelial growth factor [ VEGF ] , angiogenin , and basic fibroblast growth factor [ bFGF ] ) , tumor proteolysis factors ( urokinase type plasminogen activator [ uPA ] and plasminogen activator inhibitor 1 [ PAI 1 ] ) , and conventional tumor markers ( stage , grade , and steroid receptors ) in early breast cancer . ^^^ VEGF expression was assessed by chemiluminescence immunosorbent assay ( ICMA ) ; angiogenin , bFGF , uPA , and PAI 1 by enzyme linked immunosorbent assay ( ELISA ) ; and steroid receptors ( estrogen receptor [ ER ] and progesterone receptor [ PgR ] ) by enzyme immunoassay ( EIA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
There was no significant relationship between either of the nm 23 isoforms and cathepsin D ( Cat D ) , urokinase plasminogen activator ( uPA ) , its inhibitor ( PAI 1 ) , steroid hormone receptors or ploidy status . ^^^ We found no significant differences in Cat D , uPA , PAI 1 or uPAR , as a function of nm 23 expression in either the MDA MB 231 cells or the transfected clones . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Human endometrial stromal cell cultures , stimulated for two days with recombinant transforming growth factor beta 1 ( TGFbeta 1 ; 10 ng / ml ) , contained conditioned medium concentrations of urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and uPA : PAI 1 complex . ^^^ Since a number of cellular effects have been reported to follow a binding of enzymatically inactive uPA to the receptor in different cell types , we studied the influence of uPA : PAI 1 complex on human umbilical vein endothelial cells ( HUVEC ) and human microvascular endothelial cells ( HMEC 1 ) . ^^^ Increasing concentrations of uPA : PAI 1 complex as well as free uPA resulted in a dose dependent stimulation of endothelial cell migration . ^^^ The migratory response to both uPA and the uPA : PAI 1 complex was inhibited by antibody adhesion to the cell surface receptor for uPA . ^^^ We found that the uPA : PAI 1 complex , when released from endometrial stromal cells in response to TGFbeta 1 , stimulated endothelial cell migration . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The mRNAs of ECM degrading components urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , matrix metalloproteinase 1 ( MMP 1 ) , and tissue inhibitor of metalloproteinases 1 ( TIMP 1 ) , as well as TGFbeta 1 , bFGF , and FGFR , were detected during IVM in a factor specific pattern : all transcript levels found at COC 0 generally increased after 3 h of maturation and either remained high or decreased thereafter . ^^^ On the basis of the chosen reverse transcription polymerase chain reaction technique , one could suggest relative higher mRNA concentrations for TIMP 1 , PAI 1 , and both growth factors compared to uPA , MMP 1 , and FGFR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The combination of strong expression of PAI 1 and expression of uPA was a highly significant factor for short disease free and overall survival . ^^^ Strong PAI 1 expression was significantly associated with expression of uPA receptor or CSF 1 in the tumor epithelium , but not with standard clinical parameters , and was an independent prognostic factor for poor survival on multivariate analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The transcriptional localizations of urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and its inhibitors ( PAI 1 and PAI 2 ) , which are possibly involved in cancer metastasis , have not been determined in human lung cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Finally , target genes and proteins situated on the downstream pathway of p 53 transcription appears to be the most important factors of growth acceleration or even cell dissemination in lung cancer ( Rb and its phosphorylation pathway , Bax Bc 12 balance and matrix degrading enzymes UPA and inhibitor PAI ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A strong statistically independent prognostic impact has been attributed to uPA and its inhibitor PAI 1 in a variety of malignancies . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have reported previously that both urokinase type plasminogen activator ( uPA ) and its type 1 inhibitor ( PAI 1 ) are statistically significant prognostic variables in patients with high risk breast cancer ( Grondahl Hansen et al . , Cancer Res . , 53 : 2513 2521 , 1993 ) , and we recently described that the uPA receptor ( uPAR ) is a prognostic marker in postmenopausal , node positive breast cancer patients ( Grondahl Hansen et al . , Clin . ^^^ The present retrospective study describes the prognostic impact of uPA , its receptor uPAR , and PAI 1 in breast cancer cytosol from 111 low risk premenopausal patients and 184 low risk postmenopausal patients with a median follow up of 6 . 0 years ( range , 3 . 8 14 . 9 ) and 7 . 4 ( range , 3 . 7 14 . 0 ) years , respectively . uPA , uPAR , and PAI 1 levels were determined by sandwich enzyme linked immunosorbent assays , and data were dichotomized using the median value as the cutoff for calculation of recurrence free survival and overall survival . ^^^ The prognostic value of uPA , uPAR , and PAI 1 was then compared with that of other established prognostic variables by multivariate analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have recently described the urokinase type plasminogen activator ( uPA ) and its type 1 inhibitor ( PAI 1 ) as strong prognostic variables in breast cancer ( J . ^^^ Multivariate analysis including all patients showed that when including other biochemical variables ( estrogen receptor , progesterone receptor , PS 2 , cathepsin D , uPA , and PAI 1 ) , the only retained independent variable via backward elimination was PAI 1 for both relapse free survival and overall survival . ^^^ Multivariate analysis , including the basic model , estrogen and progesterone receptors , PS 2 , cathepsin D , uPA , PAI 1 , uPARc , and uPARt in the subgroup of postmenopausal node positive patients , showed that only uPARc and PAI 1 were significant independent prognostic parameters , with respect to overall survival , RHRs being 2 . 72 ( P < 0 . 0001 ) and 1 . 81 ( P = 0 . 005 ) , respectively . ^^^ In multivariate analysis of relapse free survival , uPARc , PAI 1 , and uPA were independent parameters with respective relative relapse rates of 1 . 91 ( P = 0 . 002 ) for uPARc , 1 . 68 ( P = 0 . 02 ) for PAI 1 , and 1 . 6 ( P = 0 . 03 ) for uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
External quality assessment of trans European multicentre antigen determinations ( enzyme linked immunosorbent assay ) of urokinase type plasminogen activator ( uPA ) and its type 1 inhibitor ( PAI 1 ) in human breast cancer tissue extracts . ^^^ High levels of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) in breast cancer tissue extracts have been associated with rapid disease progression . ^^^ In these studies , different enzyme linked immunosorbent assay ( ELISA ) kits have been applied for the quantification , and consequently the ranges of uPA and PAI 1 levels reported differ considerably . ^^^ Therefore , the Receptor and Biomarker Study Group ( RBSG ) of the European Organization for Research and Treatment of Cancer ( EORTC ) and a consortium of the BIOMED 1 project ' Clinical Relevance of Proteases in Tumor Invasion and Metastasis ' initiated three collaborative between laboratory assessment trials aimed at controlling uPA and PAI 1 antigen analyses . ^^^ Furthermore , a good parallelism following dilution was found for uPA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) in tissue and serum of head and neck squamous cell carcinoma patients . ^^^ The aim of this study was to determine urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) concentrations in tumour and adjacent normal tissue samples from 58 patients , and in serum samples from 40 of 58 patients with squamous cell carcinoma of the head and neck obtained at diagnosis and after completion of therapy . uPA and PAI 1 serum concentrations were also measured in 28 healthy volunteers who served as controls . ^^^ For both uPA and PAI 1 , significantly elevated concentrations were measured in tumour tissue as compared with normal tissue ( uPA : 8 . 89 versus 0 . 41 ng / mg total protein ( mgp ) , P < 0 . 0001 ; PAI 1 : 23 . 9 versus 1 . 47 ng / mgp , P < 0 . 0001 ) . ^^^ A statistically significant difference in uPA concentrations was found between normal laryngeal and nonlaryngeal tissue ( 0 . 52 versus 0 . 3 ng / mgp , P = 0 . 008 ) , and in PAI 1 concentrations between T 1 + 2 and T 3 + 4 stage of disease ( 17 . 32 versus 35 . 63 ng / mgp , P = 0 . 04 ) . ^^^ The uPA concentrations positively correlated with those of PAI 1 measured in both tumour ( Rs = 0 . 62 , P < 0 . 0001 ) and normal tissue ( Rs = 0 . 30 , P = 0 . 02 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here , we investigated the in vivo effect of theobromine on angiogenic activity of human urothelial cell line HCV 29 , 5 raf transfected ( mouse cutaneous assay ) , and the in vitro effect of this drug on VEGF , tPA , uPA and PAI mRNA expression in these cells ( RT PCR method ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Vascular endothelial and smooth muscle cells synthesize tissue type and urokinase type PA ( tPA and uPA ) and their major physiological inhibitor , PAI 1 . ^^^ Overexpression of uPA or deficiency of PAI 1 promotes neointima and aneurysm formation , which is probably due to active remodelling of extracellular matrix in vascular wall caused by excess plasmin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We investigated the effect of CsA therapy on the regulation of fibrinolysis in kidney graft recipients by measuring plasma concentration and activity of plasminogen activators ( tPA , uPA ) and their inhibitors ( PAI 1 , 2 ) . ^^^ We found an increase in tPA activity and in PAI 1 concentration as well as a decrease in PAI 1 activity in renal allograft recipients as compared to healthy controls , but did not confirm a correlation between these observations and CsA administration . tPA and PAI 2 concentrations as well as uPA activity did not significantly differ between the studied groups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Accumulated data indicate that endocytosis of the glycosylphosphatidyl inositol anchored protein urokinase plasminogen activator receptor ( uPAR ) depends on binding of the ligand uPA : plasminogen activator inhibitor 1 ( PAI 1 ) and subsequent interaction with internalization receptors of the low density lipoprotein receptor family , which are internalized through clathrin coated pits . ^^^ We show that uPAR with bound uPA : PAI 1 is capable of entering cells in a clathrin independent process . ^^^ First , HeLaK44A cells expressing mutant dynamin efficiently internalized uPA : PAI 1 under conditions in which transferrin endocytosis was blocked . ^^^ Third , in subconfluent nonpolarized MDCK cells , endocytosis of uPA : PAI 1 was only decreased marginally by RAP . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
When PAI 2 , purified from human cornified cells , was added to synchronized keratinocytes , S phase was no longer evident and the peak uPA activity was eliminated . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Two transfected neuroblastoma cell lines with ( WAC 2 cells ) or without ( SH EP 007 cells ) enhanced expression of the N myc oncogene were examined by zymography and RNA extraction to determine UPA and PAI enzyme activity and uPA RNA and PAI RNA expression , respectively . ^^^ The effect of genistein , an inhibitor of tyrosine protein kinase , on uPA / PAI was also investigated . ^^^ Both the uPA / PAI 1 ratio at mRNA level and the PA / PAI ratio at protein activity level were higher in the more malignant , WAC 2 cell line . ^^^ Genistein attenuated uPA activity and stimulated PAI activity in both cell lines , leading to a decrease in the PA / PAI ratio . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MC were examined by Giemsa staining and by immunohistochemistry using antibodies against tryptase , chymase , tissue type plasminogen activator ( tPA ) , urokinase ( uPA ) , urokinase receptor ( uPAR ) , and plasminogen activator inhibitors ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The very low density lipoprotein receptor ( VLDLr ) binds diverse ligands , including urokinase type plasminogen activator ( uPA ) and uPA plasminogen activator inhibitor 1 ( PAI 1 ) complex . ^^^ PAI 1 complex accelerated uPAR catabolism ( t ( 1 ) / ( 2 ) to 1 . 8 h ) , while RAP inhibited uPAR catabolism in the presence ( t ( 1 ) / ( 2 ) of 7 . 8 h ) and absence ( t ( 1 ) / ( 2 ) of 16 . 9 h ) of uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The very low density lipoprotein receptor ( VLDLR ) binds , among other ligands , the Mr 40 , 000 receptor associated protein ( RAP ) and a variety of serine proteinase serpin complexes , including complexes of the proteinase urokinase type plasminogen activator ( uPA ) with the serpins plasminogen activator inhibitor 1 ( PAI 1 ) and protease nexin 1 ( PN 1 ) . ^^^ PAI 1 , and uPA . ^^^ PAI 1 and uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In a collective of 112 node negative breast cancer patients , we compared the prognostic impact of HER 2 / neu gene amplification ( AMP ) determined by fluorescence in situ hybridization ( FISH ) and HER 2 / neu protein overexpression ( EXP ) measured by immunohistochemistry ( IHC ) with traditional prognostic factors ( tumor size , grade , steroid hormone receptor status , menopausal status ) and tumor invasion markers uPA ( urokinase type plasminogen activator ) and its inhibitor PAI 1 determined by enzyme immunoassay ( ELISA ) . ^^^ CART analysis revealed that HER 2 / neu AMP together with the combination uPA / PAI 1 allowed optimal risk group assessment after a 7 year median follow up : patients with low levels of both uPA and PAI 1 and no HER 2 / neu AMP had a significantly lower relapse rate ( 4 . 6 % ) than the remaining patients ( 32 % ) . ^^^ Combining the HER 2 / neu gene status measured by FISH with levels of tumor invasion markers uPA and PAI 1 improves clinically relevant risk group assessment . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Ninety eight patients with histologically confirmed ovarian tumors ( 77 primary ovarian carcinomas of stages T 1 to T 3 according to the postoperative histopathological classification pTNM classification , 14 ovarian metastases of various origins and seven benign ovarian tumors ) were investigated with regard to the concentration of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor ( PAI 1 ) in membrane extracts of tumors . ^^^ With more advanced stage of primary ovarian carcinomas , there was a highly significant rise in the membrane concentrations of both uPA and PAI 1 . ^^^ However , increasing dedifferentiation of the tumors correlated only with uPA , but not with PAI 1 . ^^^ There was no correlation between the number of steroid receptors for estradiol and progesterone and the content of uPA or PAI 1 in the primary ovarian carcinomas . ^^^ In the 14 ovarian metastases of different origins incluced in the study , the contents of uPA and PAI 1 were comparable to those of primary ovarian carcinomas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Prognostic impact of urokinase type plasminogen activator ( uPA ) and its inhibitor ( PAI 1 ) in cytosols and pellet extracts derived from 892 breast cancer patients . ^^^ To evaluate the clinical relevance of urokinase type plasminogen activator ( uPA ) and its type 1 inhibitor ( PAI 1 ) measured by a recently developed enzyme linked immunosorbent assay ( ELISA ) , we analysed both components in samples derived from 892 patients with primary breast cancer ( median follow up 99 months ) . ^^^ Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts ( Spearman correlation coefficient r = 0 . 60 , P < 0 . 0001 for uPA and r = 0 . 65 , P < 0 . 0001 for PAI 1 ) . ^^^ Furthermore , strong correlations were found between the levels of both uPA ( r = 0 . 85 , P < 0 . 0001 ) and PAI 1 ( r = 0 . 90 , P < 0 . 0001 ) in the cytosols and their levels previously measured with ELISAs based on commercial reagents . ^^^ In both Cox univariate and multivariate analysis , high cytosolic levels of uPA or PAI 1 were significantly associated with increased rates of relapse and death . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present paper we first compared the expression levels of uPA , tPA , PAI 1 and uPAR in a compound group consisting of 33 cancer lesions of various origin ( breast , lung , colon , cervix and melanoma ) as quantitated by ELISA and semi quantitated by IHC . ^^^ Spearman correlation coefficients between IHC results and ELISA results for uPA , tPA , PAI 1 and uPAR varied between 0 . 41 and 0 . 78 , and were higher for the compound group and the breast cancer group than for the melanoma group . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In human cancers the components of matrix degrading protease systems ( uPA , uPAR , PAI 1 and MMPs ) can be expressed by either the non neoplastic stromal cells , the cancer cells or both . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The active process of pericellular proteolysis is central in tumor invasion , and in particular the essential role of the urokinase type plasminogen activator ( uPA ) is well established . uPA mediated plasminogen activation facilitates cell migration and invasion through extracellular matrices by dissolving connective tissue components . uPA , its receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) are enriched in several types of tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Prognostic significance of urokinase ( uPA ) and its inhibitor PAI 1 for survival in advanced ovarian carcinoma stage FIGO IIIc . ^^^ We evaluated the prognostic impact of the protease urokinase plasminogen activator ( uPA ) and its inhibitor PAI 1 on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk . uPA and PAI 1 antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study . ^^^ The time varying coefficient model of Gray was used to assess the time dependent strength of prognostic factors tumour mass , uPA and PAI 1 on overall survival . ^^^ In all patients , uPA and PAI 1 ( optimized cut offs of 2 . 0 and 27 . 5 ng mg ( 1 ) protein respectively ) , in addition to the traditional prognostic parameters of residual tumour mass , nodal status , grading and ascites volume , were of prognostic significance in univariate analysis for overall survival . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We show here that hK 2 rapidly forms a complex with plasminogen activator inhibitor 1 ( PAI 1 ) , the primary inhibitor of uPA in tissues . ^^^ Our current results suggest that the increased hK 2 expression in prostate cancer tissues could influence cancer biology not only by activation of uPA but also by inactivation of its primary inhibitor , PAI 1 . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Studies carried out over the past 10 years in a number of laboratories have elucidated some of the biochemical events related to the function and regulation of the PA system in the ovary : hormone induced proteolytic activity provided by tissue type PA ( tPA ) and modulated by PAI 1 in the preovulatory follicles is responsible for a controlled and directed proteolysis leading to rupture of selected follicles during ovulation , whereas the coordinated expression of urokinase type PA ( uPA ) and PAI 1 in the early growing follicle may be important in ECM degradation during cell proliferation and migration ; the PA system may also play a role in the control of corpus luteum ( CL ) development through an autocrine or paracrine mechanism . ^^^ Increase in tPA and PAI 1 expression in CL at a later stage is well correlated with a sharp decrease in CL progesterone production , while the increase in uPA mRNA levels and activity in the early stage of CL development is correlated with an increase in progesterone secretion . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TGF beta appeared to induce also membrane bound uPA activity and the release of active plasminogen activator inhibitor 1 , indicating that TGF beta has the potential to regulate plasminogen activation at the RPE cell surface . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The present study compares plasma urokinase plasminogen activator ( uPA ) peptide levels , plasma plasminogen inhibitor ( PAI 1 ) activity and urokinase receptors ( uPAR ) on peripheral blood monocytes of patients with stable coronary artery disease ( SCAD ) and healthy volunteers . 2 . ^^^ The data indicate a pattern of expression / activity of uPA and PAI 1 in patients with SCAD suggestive of an impaired fibrinolytic ability . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : To evaluate whether cathepsin D , urokinase type plasminogen activator ( uPA ) , its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) , or clinical factors can predict which patients are at risk for developing distant metastases after local recurrence ( LR ) . ^^^ From the available primary tumor tissues , we determined the cytosolic levels of cathepsin D , uPA and PAI 1 . ^^^ The primary tumor levels of uPA and PAI 1 were elevated for patients with a short DFI ( P < . 01 ) , but such a relation was not observed for patients with skin involvement . ^^^ In univariate analyses , high levels of uPA and PAI 1 in the primary tumor were associated with poor PR OS ( P = . 038 and P = . 040 , respectively ) but not PR DMFS . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Specific monkey cRNA and antibodies against human tPA , uPA , PAI 1 and PAI 2 were used as probes . ^^^ It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA , uPA , PAI 1 and PAI 2 to differing extents . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These phenotypic changes were associated with reduced expression levels of the endogenous urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) genes , the products of which are implicated in the control of cell adhesion and invasion . ^^^ In patients , high expression levels of uPA and PAI 1 correlate with poor prognosis . ^^^ Thus , reduced expression of uPA and PAI 1 is consistent with suppression of tumorigenicity in DPC 4 reconstituted cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The presence of the two plasminogen activators ( PAs ) , tissue type plasminogen activator ( tPA ) , and urokinase type plasminogen activator ( uPA ) , and their inhibitor type 1 ( PAI 1 ) in bone cells , suggests a role in one or more aspects of bone resorption such as osteoclast formation , mineral dissolution , and degradation of the organic matrix . ^^^ These different processes were assayed in vitro using cells derived from mice with either tPA ( tPA / ) , uPA ( uPA / ) , PAI 1 ( PAI 1 / ) inactivation or with a combined inactivation ( tPA / : uPA / ) and compared with wild type mice ( WT ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Changes in urokinase plasminogen activator ( uPA ) , tissue like plasminogen activator ( tPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) immunoreactivity were also assessed . ^^^ Endothelial tPA immunoreactivity decreased significantly after irradiation ( P < 0 . 001 ) , whereas uPA and PAI 1 immunoreactivity levels appeared to be unchanged . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TGF beta 1 enhanced uPA production , the number of uPA cell surface binding sites , and the expression of the plasminogen activator inhibitor PAI 1 , in transformed PDV cells , but had no major effect on nontumorigenic MCA3D keratinocytes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Furthermore , uPA is prognostic in node negative patients , and a clinical trial is currently under way to assess whether uPA and its inhibitor , plasminogen activator inhibitor 1 , can differentiate between the majority of node negative breast cancer patients who are cured by surgery from the minority who might benefit from adjuvant therapy . uPA is also prognostic in other malignancies , such as gastric , colorectal , esophageal , renal , endometrial , and ovarian cancers . uPA may thus be a prognostic indicator for multiple types of adenocarcinoma . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cytosolic determinations of cathepsin D ( cath D ) , urokinase plasminogen activator ( uPA ) and its specific inhibitor PAI 1 have shown an association with adverse prognosis in breast cancer . ^^^ Nearly all tumours expressed uPA and PAI 1 , which were categorized to cytoplasmic expression in carcinoma cells and diffuse stromal expression and quantified / + / ++ / and further dichotomized for purposes of analysis . ^^^ Expression of uPA and PAI 1 in stromal fibroblasts was recorded as / + . ^^^ However , no consistent association between the immunohistochemically quantified uPA and PAI 1 and prognosis was found . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Factors reflecting two major aspects of tumour biology , invasion ( urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibiter ( PAI 1 ) , cathepsin D ) and proliferation ( S phase fraction ( SPF ) , Ki 67 , p 53 , HER 2 / neu ) , were assessed in 125 node negative breast cancer patients without adjuvant systemic therapy . ^^^ Antigen levels of uPA , PAI 1 and cathepsin D were immunoenzymatically determined in tumour tissue extracts . ^^^ Univariate analysis determined PAI 1 ( P < 0 . 001 ) , uPA ( P = 0 . 008 ) , cathepsin D ( P = 0 . 004 ) and SPF ( P = 0 . 023 ) as significant for DFS . ^^^ In CART analysis for DFS , the combination of PAI 1 and uPA gave the best risk group discrimination . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) were determined by the ELISA assay . ^^^ Concentrations of uPA and PAI 1 were increased in CT cells , with no change in AT cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The prognostic impact of invasion markers PAI 1 and urokinase type plasminogen activator ( uPA ) on disease free survival ( DFS ) and overall survival ( OS ) in breast cancer has since been independently confirmed . ^^^ We now report on the prognostic impact of PAI 1 and uPA after long term median follow up of 77 months for our cohort ( n = 316 ) . ^^^ Levels of uPA , PAI 1 , and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods . ^^^ Using log rank statistics , optimized cutoffs were found for PAI 1 ( 14 ng / mg ) , uPA ( 3 ng / mg ) , cathepsin D ( 41 pmol / mg ) , and SPF ( 6 % ) . ^^^ In all patients , various factors ( PAI 1 , uPA , nodal status , SPF , cathepsin D , grading , tumor size , hormone receptor status ) showed significant univariate impact on DFS . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor ( PAI 1 ) , a member of the serine protein family , is the most active in vivo inhibitor of fibrinolysis induced by plasminogen , tissue plasminogen activator ( tPA ) , and urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of uPA , uPA receptor , and plasminogen activator inhibitor 1 were determined by Western blot and enzyme linked immunosorbent assay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor ( PAI ) 1 , a serine protease inhibitor , inactivates urokinase type plasminogen activator ( uPA ) and regulates degradation of the extracellular matrix ; whether it functions for or against tumor progression , however , has been the subject of controversy . ^^^ These results suggest that PAI 1 plays a role in inhibiting invasion and proliferation , and the balance between uPA and PAI 1 expression is important to assess the invasiveness of HCC cells . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) expression was determined by enzyme linked immunosorbent assay . ^^^ We conclude that TSP 1 , in a receptor mediated process that involves the activation of TGF beta 1 , upregulates PAI 1 expression in pancreatic cancer without an effect on uPA production . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) system plays an important role in tumor cell invasion , metastases , and angiogenesis . uPA , uPA receptor , and plasminogen activator inhibitor 1 ( PAI 1 ) are prognostic factors in different solid tumors , e . g . , renal cell carcinomas ( RCCs ) . von Hippel Lindau ( VHL ) disease is an inherited cancer syndrome that is characterized by extensively vascularized tumors , including hemangioblastomas and RCCs . ^^^ It has been recognized in sporadic RCC that PAI 1 mRNA levels are up regulated and uPA mRNA levels are down regulated . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Experiments have demonstrated that some other components , except UPA itself , can be very important in this process , including UPA receptor ( UPAR ) and UPA inhibitors PAI 1 and PAI 2 . ^^^ Clinical retrospective studies using predominantly ELISA techniques have shown that the high levels of UPA , PAI 1 and UPAR in the tumor tissue are associated with poor prognosis both for overall and for disease free survival of breast cancer patients , and the elevated level of PAI 2 may be indicative of better survival . ^^^ UPA and PAI 1 are now regarded as rather potent independent predictors in breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cysteine proteases [ Cathepsin B and L ( CATB , CATL ) ] and the serine protease urokinase type plasminogen activator ( UPA ) with its inhibitor type 1 ( PAI 1 ) are thought to play an important part in colorectal cancer invasion and metastasis . ^^^ Significantly higher antigen levels were found : 1 . in cancerous tissue vs . tumour free tissue ( CATB , CATL , UPA , PAI 1 ) ; in colorectal cancer with vs . without metastasis ( CATB , CATL , UPA , PAI 1 ) ; 3 . in poorly vs . well differentiated tumours ( CATB , UPA , PAI 1 ) ; 4 . in advanced Dukes ' stages ( CATB , UPA , PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To identify regions responsible for ligand recognition , soluble receptor fragments containing the eight cysteine rich class A repeats were produced . ( 125 ) 1 RAP and ( 125 ) 1 labeled urokinase type plasminogen activator : plasminogen activator inhibitor type 1 ( uPA : PAI 1 ) complexes bound to the soluble fragment with K ( D , app ) values of 0 . 3 and 14 nM , respectively . ^^^ Deletion analysis demonstrate that high affinity RAP binding requires the first four cysteine rich class A repeats ( L 1 4 ) in the VLDL receptor while the second repeat ( L 2 ) appears responsible for binding uPA : PAI 1 complexes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : To study interactions between disease free survival ( DFS ) and four components of the plasminogen activator system : urokinase type plasminogen activator ( uPA ) , its two inhibitors ( PAI 1 and PAI 2 ) , and its membrane receptor uPAR . ^^^ PATIENTS AND METHODS : We conducted a retrospective study of 499 primary breast cancer patients ( median follow up , 6 years ) . uPA , PAI 1 , and PAI 2 were determined on cytosols and uPAR on solubilized pellets , using enzyme linked immunoadsorbent assay kits ( American Diagnostica , Greenwich , CT ) . ^^^ RESULTS : By univariate analysis , higher uPA and PAI 1 values were significantly related to shorter DFS ( P = . 002 ; P < . 00002 ) . ^^^ Multiple correspondence analysis showed the parallel impact of uPA and PAI 1 on outcome , and the clearly different behavior of PAI 2 compared with PAI 1 . ^^^ A dissemination risk index [ uPA 10 PAI 1 / ( PAI 2 + 1 ) ] , taking into account the modulation of uPA proteolytic activity by the ratio of its two inhibitors , was then tested . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : Cathepsin B ( CATB ) and cathepsin L ( CATL ) , which are cysteine proteases , urokinase ( UPA ) and tissue type plasminogen activator ( TPA ) , both serine proteases , and their inhibitor type 1 ( PAI 1 ) are believed to play an important role in colorectal carcinoma ( CRC ) invasion and metastasis . ^^^ The objective of this study was to measure CATB , CATL , UPA , TPA , and PAI 1 in the same cancerous tissue ( CANCER ) and in tissues obtained from a tumor free area ( NORMAL ) to compare their respective prognostic roles in patients with CRC . ^^^ RESULTS : Significantly higher antigen levels were found : 1 ) in CANCER versus NORMAL ( with respect to CATL , UPA , and PAI 1 , with significantly lower levels for TPA ) ; 2 ) in CRC with versus without metastasis ( CATB , CATL , and PAI 1 ) ; 3 ) in poorly versus well differentiated CRC ( UPA and PAI 1 ) ; and 4 ) in advanced Dukes stages ( PAI 1 ) . ^^^ CATB and CATL significantly correlated with UPA and PAI 1 . ^^^ Finally , CATL ( P = 0 . 0001 ) , UPA ( P = 0 . 006 ) , PAI 1 ( P = 0 . 006 ) , Dukes stage ( P = 0 . 0001 ) , presence of metastases ( P = 0 . 003 ) , and vascular invasion ( P = 0 . 03 ) had a significant prognostic impact . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODOLOGY : We immunohistochemically examined 97 colorectal carcinomas for the expression of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) to investigate whether uPA and PAI 1 expressions could serve as prognostic parameters ; the gene expression of uPA and PAI 1 in human colon cancer tissues was also analyzed using reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ RESULTS : The relative expression levels of uPA and PAI 1 mRNAs were well correlated with immunoreactivities of uPA and PAI 1 , respectively ( p < 0 . 05 ) . ^^^ In immunohistochemical staining , diffuse specific staining was observed in the cytoplasm of carcinoma cells . uPA expression was detected in 57 carcinoma specimens ( 58 . 8 % ) and PAI 1 expression was detected in 36 specimens ( 37 . 1 % ) . ^^^ With regard to 5 year overall survival rate , patients whose tumors had positive uPA and negative PAI 1 immunoreactivities had a significantly poorer prognosis ( p < 0 . 05 ) . ^^^ In multivariate analysis , the combined variable of uPA and PAI 1 was shown to be an independent prognostic indicator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Levels of uPA and PA inhibitor 1 ( PAI 1 ) levels were determined under basal conditions and after IGF 1 stimulation in conditioned media from osteoblasts by enzyme linked immunosorbent assay . ^^^ Addition of plasminogen promoted uPA activity in both normal and OA osteoblasts via a positive feedback loop due to plasmin generation , since this activity was inhibited by both PAI 1 and alpha 2 antiplasmin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
There is evidence that serine proteases , such as tissue plasminogen activator ( TPA ) , urokinase type plasminogen activator ( UPA ) , and plasminogen activator inhibitor ( PAI ) , are involved in this process . ^^^ Vitreous levels of VEGF , TPA , UPA , and PAI were determined by enzyme linked immunosorbent assay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Changes in the expression of this system , consisting of urokinase and tissue type plasminogen activators ( uPA and tPA , respectively ) , plasminogen activator inhibitors ( PAI 1 , PAI 2 ) and uPA receptor , have been associated with tumour aggressiveness in a variety of solid malignant tumours . ^^^ PAI 1 transcripts were found in stromal cells of most tissue samples with , however , significantly increased levels in invasive SCC compared with SIL , microinvasive SCC , and normal mucosa . uPA positive invasive carcinomas often displayed additional PAI 1 expression by tumour cells . ^^^ In the majority of SCCs tested ( 27 / 29 cases ) , the HPV 16 E6 / E7 oncogene and uPA transcription were correlated . uPA and PAI 1 expression indicates invasive growth when expressed by atypical epithelial cells of squamous cervical lesions . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Gene expression for plasminogen activator inhibitor 1 ( PAI 1 ) , urokinase and tissue plasminogen activators ( uPA and tPA ) , urokinase plasminogen activator receptor ( uPAR ) , and transforming growth factor beta 1 ( TGF beta 1 ) was examined by Northern analysis . ^^^ Western analysis was performed to detect protein expression of PAI 1 , uPA and uPAR . ^^^ RESULTS : At 6 weeks , when fibrosis had occurred , uPA and uPAR mRNAs had increased 2 . 8 fold and 1 . 8 fold , respectively ; PAI 1 and tPA mRNA levels were unchanged . ^^^ At the cirrhotic stage ( 9 to 12 weeks ) , mRNA levels for PAI 1 , uPA , uPAR and tPA were all increased . ^^^ Western analysis also showed increased uPA and uPAR expressions in fibrotic liver , and increased PAI 1 , uPA and uPAR expressions in cirrhotic liver . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We investigated the production by leukaemic cells of plasminogen activators [ urokinase ( uPA ) and tissue type PA ( tPA ) ] , cell surface receptor for uPA ( uPAR ) and PA inhibitors ( PAI 1 and PAI 2 ) . ^^^ The finding of uPA , uPAR , PAI 1 and PAI 2 synthesized by leukaemic cells suggests that plasminogen activation may contribute to the invasive behaviour of these cells , the fibrinolytic imbalance observed in leukaemic patients and the differentiation and proliferation of M 4 M5 by interaction of uPA with uPAR . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In RT PCR experiments , tissue type PA ( tPA ) mRNA levels in both aged hGF and rGF were higher than in young cells , whereas plasminogen activator inhibitor 1 ( PAI 1 ) mRNA remained unchanged and urotype PA ( uPA ) mRNA was not detected . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The correlation between p 53 and PAI 1 as well as between UPA and PAI 1 was highly significant . ^^^ According to the Kaplan Meier estimations , Ki 67 , UPA and PAI 1 had no influence on survival in our group of patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : All uPAR , uPA , PAI 1 , and PAI 2 antigen levels in tumor tissue were significantly higher than those in normal tissue . ^^^ Significant positive correlation coefficients ( r ) were obtained between tumor size and the calculated ratios of PAI 1 / uPAR ( r = 0 . 490 ; P < 0 . 0001 ) and PAI 1 / uPA ( r = 0 . 469 ; P < 0 . 0001 ) . ^^^ CONCLUSIONS : Higher expression of uPAR was related to poor prognosis of patients with colorectal carcinoma and excess amounts of PAI 1 over uPAR or uPAR bound uPA appeared to play an important role in tumor progression . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MATERIALS AND METHODS : In the present study , we determined the plasma concentrations of tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , PAI 2 , and uPA receptor ( uPAR ) in 25 patients with ovarian cancer , 16 patients with benign gynecologic tumor or inflammation , and 36 healthy controls in order to find out whether the plasma levels of these markers could be used to evaluate the prognostic value in patients with gynecologic cancers . ^^^ Tissue concentrations of uPA , PAI 1 , and PAI 2 were significantly higher and tPA significantly lower in the malignant tumor tissue than in the cut end tissue in the patients with ovarian cancer ( P = 0 . 014 , 0 . 03 , 0 . 002 , and 0 . 01 , respectively ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Additionally , we considered the secretion of urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 and 2 ( PAI 1 and PAI 2 ) , as well as matrix metalloproteinases ( MMP ) 1 , 2 , 3 , and 9 , and their inhibitors TIMP 1 and TIMP 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , the major circulating inhibitor of urokinase [ urokinase type plasminogen activator ( uPA ) ] , has been linked to the pathogenesis of lung cancer . ^^^ PAI 1 belongs to the serpin family of inhibitors and inhibits both free urokinase ( uPA ) and receptor bound urokinase ( uPA receptor ) . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) , the major circulating inhibitor of urokinase [ urokinase type plasminogen activator ( uPA ) ] , has been linked to the pathogenesis of lung cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TGF beta 1 induces uPA and PAI 1 secretion and promotes binding of uPA at the external plasma membrane with increased membrane associated plasmin activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The association between drug resistance and three markers for invasive capacity : cathepsin D ( Cath D ) , urokinase type plasminogen activator ( uPA ) and inhibitor of plasminogen activator type 1 ( PAI 1 ) was examined in nine cervical and laryngeal carcinoma cell lines resistant to different cytostatics . ^^^ The level of Cath D was measured by solid phase two site immunoradiometric assay , while uPA and PAI 1 concentrations were determined by use of ELISA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To study this supposition , we investigated immunohistochemically the expression of tPA , uPA and its receptor , the plasminogen activator inhibitors PAI 1 and PAI 2 , tetranectin as well as the laminin breakdown as an event of secondary brain injury . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study involving 2780 patients with primary invasive breast cancer , we have evaluated the prognostic importance of the four major components of the uPA system [ uPA , the receptor uPAR ( CD 87 ) , and the inhibitors PAI 1 and PAI 2 ] . ^^^ The levels of the four factors significantly correlated with each other ; the Spearman rank correlation coefficients ( r ( s ) ) ranged from 0 . 32 ( between PAI 2 and PAI 1 or uPAR ) to 0 . 59 ( between uPA and PAI 1 ) . ^^^ In the multivariate analyses for relapse free survival ( RFS ) and overall survival ( OS ) , we defined a basic model including age , menopausal status , tumor size and grade , lymph node status , adjuvant therapy , and steroid hormone receptor status . uPA , uPAR , PAI 1 , and PAI 2 were considered as categorical variables , each with two cut points that were established by isotonic regression analysis . ^^^ Compared with tumors with low levels , those with intermediate and high levels showed a relative hazard rate ( RHR ) and 95 % confidence interval ( 95 % CI ) of 1 . 22 ( 1 . 02 1 . 45 ) and 1 . 69 ( 1 . 39 2 . 05 ) for uPA , and 1 . 32 ( 1 . 14 1 . 54 ) and 2 . 17 ( 1 . 74 2 . 70 ) for PAI 1 , respectively , in multivariate analysis for RFS in all patients . ^^^ Furthermore , uPA and PAI 1 were independent predictive factors of a poor RFS and OS in node negative and node positive patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Aged hPLF cells produced a significantly higher PA activity when compared with those of young hPLF cells in response to MTF in a time and magnitude dependent manner . tPA mRNA levels in aged cells were higher than those in young cells , whereas PAI 1 mRNA remained unchanged and uPA mRNA was not detected . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We found that overexpression of E2F1 3 , which acts mainly in late G ( 1 ) , inhibits promoter activity and endogenous expression of the urokinase type PA ( uPA ) and PA inhibitor 1 ( PAI 1 ) genes . ^^^ Interestingly , an E2F1 mutant lacking the pRB binding region strongly repressed the uPA and PAI 1 promoters . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the solid tumor , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and uPA receptor ( uPAR ) are considered as prognostic factors . ^^^ In this study , we have investigated whether secretion of the uPA , PAI 1 and uPAR from the primary breast cancer tissue can be detected in the blood of the patients using the ELISA assay . ^^^ We have found that the plasminogen activation system ( uPA , PAI 1 , uPAR ) of tumor tissue is activated from the early stage of breast cancer . ^^^ The blood level of the plasminogen activation system correlated with that of tissue in an order of uPAR ( r ( 2 ) =0 . 61 ; P=0 . 001 ) , uPA ( r ( 2 ) =0 . 35 ; P=0 . 001 ) and PAI 1 ( r ( 2 ) =0 . 11 ; P=0 . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , higher hypercoagulation evidenced by significantly raised prothrombin formation and clot elasticity together with higher levels of D dimer , uPA antigen and PAI 1 than observed in normal pregnancy suggests a hyperfibrinolytic / inhibitor state in hydrops fetalis pregnancy associated with bad obstetric outcome . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In situ hybridization and immunocytochemical localization were used to define the cellular and tissue distribution of urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and 2 ( PAI 2 ) and urokinase receptor in early monkey placenta and uterus . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The results from the biochemical analysis of tissue samples , from each form of biopsy , with respect to estradiol and progesterone receptor , UPA and PAI 1 , as well as Kathepsin D and the EGF receptor , were compared and statistically analyzed . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase type plasminogen activator system ( uPAS ) , consisting of the urokinase plasminogen activator ( uPA ) , the uPA receptor ( uPA R ) , and their corresponding inhibitors , PAI 1 and PAI 2 , is thought to play a role in this process . ^^^ In KS , we observed positive immunostaining in 16 of 31 ( 51 . 6 % ) cases for uPA R , in 11 of 31 ( 35 . 5 % ) cases for uPA , in 3 of 31 ( 9 . 6 % ) cases for PAI 1 , and in 2 of 31 ( 6 . 4 % ) cases for PAI 2 . ^^^ The GP cases showed the following positive results : 4 of 25 ( 16 % ) for uPA R , 6 of 25 ( 24 % ) for uPA , 10 of 25 ( 40 % ) for PAI 1 , and 11 of 25 ( 44 % ) for PAI 2 . ^^^ The upregulation of uPA and its corresponding receptor , uPA R , in AS and KS supports the hypothesis of the proliferative nature of these lesions ; however , the upregulation of the inhibitors ( PAI 1 and PAI 2 ) in benign and reactive proliferative angiomatous lesions ( GP and AN ) shows how this process may be limited . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumor biological factors uPA and PAI 1 as stratification criteria of a multicenter adjuvant chemotherapy trial in node negative breast cancer . ^^^ In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA ( urokinase type plasminogen activator ) and its inhibitor PAI 1 ( plasminogen activator inhibitor type 1 ) in node negative breast cancer patients . ^^^ Since then , patients have been followed up in order to assess the value of uPA and PAI 1 determination as an adequate selection criterion for adjuvant chemotherapy in node negative breast cancer patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
After long term follow up , the prognostic impact of the following proteolytic factors associated with tumor invasion and metastasis was evaluated in 276 primary breast cancer patients : uPA ( urokinase type plasminogen activator ) , PAI 1 ( uPA inhibitor type 1 ) , and cathepsins B , D and L . ^^^ Antigen levels of uPA and PAI 1 were determined by ELISA in detergent extracts ; cathepsin B , D , and L content was determined in cytosol fractions of the primary tumor : cathepsin D by ELSA and cathepsin B and L by ELISA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The inputs to the neural network include classical factors such as grading , age , tumor size , estrogen and progesterone receptor measurements , as well as tumor biological markers such as PAI 1 and uPA . ^^^ The use of neural network analysis and scoring in combination with strong tumor biological factors such as uPA and PAI 1 appears to result in a very effective risk group discrimination . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Predictive value of uPA , PAI 1 , HER 2 and VEGF in the serum of ovarian cancer patients . ^^^ BACKGROUND : Tissue levels of uPA , PAI 1 , HER 2 and VEGF are known to have prognostic value in different malignant tumors . ^^^ RESULTS : Correlations were observed between VEGF and CA 125 , HER 2 ( inversely ) as well as PAI 1 , and between uPA and PAI 1 . ^^^ CONCLUSIONS : Serum levels of uPA , PAI 1 , HER 2 and VEGF do not have enough predictive potential in recurrent ovarian cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MDCK cells transformed by LMP 1 showed invasive growth to form branching tubules into collagen gel without HGF treatment . mRNA differential display and Northern hybridization identified plasminogen activator inhibitor 1 ( PAI 1 ) , urokinase type plasminogen activator ( uPA ) and ets 1 as genes upregulated during transformation by LMP 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Coordinate regulation of the serpin plasminogen activator inhibitor 1 was also apparent ; however , a net increase in uPA activity was predominant . alpha ( 3 ) beta ( 1 ) integrin clustering induced extracellular signal regulated kinase 1 / 2 phosphorylation , and both uPA induction and extracellular signal regulated kinase activation were blocked by the mitogen activated protein kinase / extracellular signal regulated kinase kinase inhibitor PD 98059 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : We used a recently developed method for making precise distance measurements , based on donor donor energy migration ( DDEM ) , to accurately triangulate the position of the protease urokinase type plasminogen activator ( uPA ) in complex with the serpin plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : Urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and plasminogen activator inhibitors ( PAI 1 and PAI 2 ) , all play important roles in tumour invasion and metastasis . ^^^ PATIENTS AND METHODS : The levels of uPA , uPAR PAI 1 and PAI 2 were measured by enzyme linked immunosorbent assay ( ELISA ) in triton extracts , prepared from 88 NSCLC tissues ( stage 1 IIIa ) and 74 normal lung tissues from the same patients . ^^^ RESULTS : The expression levels of uPA , uPAR , PAI 1 and PAI 2 were significantly higher in tumour tissues as compared to their normal equivalents ( all , P < 0 . 0001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Furthermore , the levels of secreted plasminogen activator inhibitor 1 ( PAI 1 ) were markedly higher , while no apparent differences were seen in the levels of active uPA and tPa between EGF R ( / ) and wild type pancreata . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The purpose of this study was to evaluate the effects of 4 HPR on uPA and plasminogen activator inhibitor 1 ( PAI 1 ) in prostate cancer . ^^^ Administration of 10 ( 6 ) M 4 HPR for 3 days resulted in an increase in uPA mRNA expression ( TSU PR 1 : 391 % , PC 3 : 356 % ) , and a simultaneous increase in PAI 1 mRNA expression ( TSU PR 1 : 217 % , PC 3 : 235 % ) was observed . ^^^ Concentrations below 10 ( 6 ) M failed to alter the protein production of either uPA or PAI 1 . ^^^ The functional uPA assay demonstrated a reduction of the proteolytic activity of uPA ( TSU PR 1 : 13 % , PC 3 : 7 % ) in cell lysates of 10 ( 6 ) M 4 HPR ( p < 0 . 05 ) , while there was minimal uPA activity in the conditioned media . 4 HPR stimulates a paradoxical increase in uPA and PAI 1 , but the anti invasive effects of 4 HPR are consistent with the increase in both uPA and PAI 1 , resulting in an overall reduction of functional uPA activities . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To evaluate the most effective factor in the invasion , metastasis and prognosis of hepatocellular carcinoma ( HCC ) , we examined urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor ( PAI ) 1 , PAI 2 and uPA activity by enzyme linked immunosorbent assays ( ELISA ) in HCC tissues obtained from 46 patients . ^^^ The levels of uPA , PAI 1 and PAI 2 antigens were significantly associated with INV and histological grade . ^^^ The DFS was not different , however , between cases with uPA , PAI 1 and PAI 2 values above and below the median . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
High amounts of p 185 were significantly associated with a high expression of urokinase type plasminogen activator ( uPA ) ( P < . 010 ) , uPA receptor ( P = . 030 ) , type 1 plasminogen activator inhibitor ( PAI ) ( P < . 010 ) , type 2 PAI ( P = . 021 ) , cathepsin D ( P = . 036 ) , matrix metalloproteinase 2 ( P = . 024 ) , alpha 1 antichymotrypsin ( P = . 025 ) , and alpha 2 macroglobulin ( P = . 017 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Since reported data have indicated that plasminogen activators ( uPA and tPA ) were able to excise the angiostatin fragment from the plasminogen parent molecule via plasmin generation , we determined levels of uPA and tPA and PAI 1 antigen in the conditioned media , and correlated the results with angiostatin generating capacity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The distances found were 57+ / 4 A and 63+ / 3 A , respectively , which is comparable to the distance obtained between the same residues when PAI 1 is in complex with urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
It has become more and more clear in recent decades that the plasminogen activation system , which includes urokinase type plasminogen activator ( uPA ) , urokinase type plasminogen activator receptor ( uPAR ) , plasminogen activator inhibitor ( PAI ) 1 and PAI 2 , plays a very important role in the aggressiveness of cancer . ^^^ The positive rates of uPA , uPAR , PAI 1 and PAI 2 for immunohistochemical stains in cancer tissues were 78 . 9 , 68 . 4 , 57 . 9 and 31 . 6 % , respectively . ^^^ In ELISA , there were significant differences between cancer and non cancer tissues in concentration of uPA , uPAR and PAI 1 ( P < 0 . 0003 , 0 . 0024 and 0 . 01 , respectively ) , but there was no significant difference in that of PAI 2 ( P = 0 . 37 ) . ^^^ These results suggest that uPA , uPAR and PAI 1 are related to invasion of HCC . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both isoforms ( alpha and beta ) of IL 1 ( interleukin 1 ) increased as cells approached crisis , and the presence of these cytokines may be responsible for the increased levels of tPA , PAI , and uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPA R ) and inhibitors ( PA 1 1 ) expression in hepatocellular carcinoma in relation to cancer invasion / metastasis and prognosis ] . ^^^ OBJECTIVE : To study the relevance of uPA , uPA R and PA 1 1 to hepatocellular cancer ( HCC ) . ^^^ METHODS : The expression at protein level for uPA , uPA R and PA 1 1 was examined in 48 cases of HCC and 12 cases of benign tumors of the liver ( as control ) immunohistochemically . ^^^ RESULTS : When compared to HCC adjacent normal liver tissue and the control , positive rates of immune staining for uPA , uPA R and PA 1 1 on cell membrane were significantly higher in HCC cells ( P < 0 . 05 ) . ^^^ In 36 cases who survived , 17 was positive for uPA R and 15 for PA 1 1 , while in 12 cases who died 2 years after surgery , 12 and 9 cases were positive for uPA R and PA 1 1 , respectively ( P < 0 . 01 and < 0 . 05 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We studied the expression of uPA , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor type 1 ( PAI 1 ) in human breast carcinomas and their bone metastases , using in situ hybridisation . ^^^ The majority of the tumours examined expressed low to moderate levels of uPA mRNA and low to high levels of uPAR and PAI 1 mRNA , which was predominantly localised to the epithelial tumour cells . ^^^ There was slight over expression of uPA and PAI 1 mRNA and a marked increase in uPAR mRNA expression in the malignant tumours compared with benign tissue . ^^^ Overall , uPAR and PAI 1 mRNA expression was found to be more variable than uPA mRNA , suggesting a possible role of the receptor and inhibitor in the regulation of uPA activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factors such as uPAR and growth factors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activation system also includes the serpins PAI 1 and PAI 2 , and the uPA receptor ( uPAR ) . ^^^ Moreover , the system also supports cell migration and invasion by plasmin independent mechanisms , including multiple interactions between uPA , uPAR , PAI 1 , extracellular matrix proteins , integrins , endocytosis receptors , and growth factors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
For this purpose , the presence and enzymatic activity of matrix metalloproteinases ( MMP 2 , MMP 9 ) , tissue inhibitors of MMPs ( TIMP 1 , TIMP 2 ) , urokinase type ( uPA ) and tissue type ( tPA ) plasminogen activators ( PAs ) , and plasminogen activator inhibitor 1 ( PAI 1 ) were quantified by western blot and gelatin or plasminogen casein zymography . ^^^ Levels of PAs ( uPA and tPA ) as well as PAI 1 were both lower in varicose veins ( p < 0 . 005 ) , with minimal change in the PAI / PA ratio . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A large number of molecular biological factors have been shown to have prognostic significance in breast cancer e . g . c erbB 2 , p 53 , uPA , PAI 1 and VEGF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We compared two methods that measure plasminogen activator inhibitor ( PAI ) activity in plasma based on the ability of PAI to inhibit tissue plasminogen activator ( tPA ) or urokinase ( uPA ) in order to determine which method most accurately measures plasma PAI activity after stressors , like hemorrhage . ^^^ Using standard curves derived from rhPAI 1 , we found that the tPA PAI assay was more sensitive than the uPA PAI assay . ^^^ However , we measured a 10 fold difference in PAI activity as measured between assays , suggesting that some endogenous plasma constituents ( tPA , uPA , plasminogen or plasmin ) may interfere with the accurate determination of PAI activity . ^^^ The uPA PAI assay does not have this confounding problem because endogenous uPA does not interfere with the assay , nor does it rise during hemorrhage . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The serine protease urokinase type plasminogen activator ( uPA ) , its inhibitor ( PAI 1 ) , and its receptor ( uPAR ; CD 87 ) facilitate cancer cell invasion and metastasis . ^^^ Whereas uPA and PAI 1 antigen levels determined in tumor tissue extracts of breast cancer patients correlate with disease recurrence and overall survival , the prognostic relevance of uPAR is still a matter of debate . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this paper we describe the expression of the tissue plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and the uPA receptor ( uPAR ) , in normal and atheromatous human vascular tissue obtained at coronary and peripheral vascular surgery . tPA , uPA , PAI 1 and uPAR antigens were localised by immunohistochemistry . ^^^ Vessel homogenates were used to quantitate tPA , uPA and PAI 1 antigens as well as uPA and PAI 1 activities using immunoassay and immunoactivity assays , respectively . ^^^ Quantitative reverse transcription polymerase chain reaction assays ( PAI 1 and uPA ) were developed and used to quantify PAI 1 and uPA mRNA . ^^^ In situ hybridisation ( tPA , uPA and PAI 1 ) was used to localise mRNA . ^^^ In normal saphenous vein or internal mammary artery , expression of tPA , uPA and PAI expression is associated with endothelium and with intimal or medial smooth muscle cells , but expression is at a low level . uPAR protein was seen on the endothelium of normal saphenous vein or internal mammary artery but absent on the smooth muscle cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Since the urokinase type plasminogen activator ( uPA ) initiates this cascade , this hypothesis was tested by investigating the effects of noncytotoxic levels of nickel subsulfide on the balance of uPA expression relative to expression of its inhibitor , PAI 1 , in cultured human bronchial epithelial cells ( BEAS 2B ) . ^^^ Despite partial recovery of uPA protein levels , uPA activity remained depressed for more than 48 h after exposure to nickel due to the continued increase in PAI 1 expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Although fragments of the extracellular matrix component hyaluronan induce macrophage production of inflammatory mediators , the effect of hyaluronan on the fibrinolytic mediators plasminogen activator inhibitor ( PAI ) 1 and urokinase type plasminogen activator ( uPA ) is unknown . ^^^ This study demonstrates that hyaluronan fragments augment steady state mRNA , protein , and inhibitory activity of PAI 1 as well as diminish the baseline levels of uPA mRNA and inhibit uPA activity in an alveolar macrophage cell line . ^^^ Hyaluronan fragments alter macrophage expression of PAI 1 and uPA at the level of gene transcription . ^^^ Similarly , hyaluronan fragments augment PAI 1 and diminish uPA mRNA levels in freshly isolated inflammatory alveolar macrophages from bleomycin treated rats . ^^^ These data suggest that hyaluronan fragments influence alveolar macrophage expression of PAI 1 and uPA and may be a mechanism for regulating fibrinolytic activity during lung inflammation . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , plasminogen ( Plg ) , and plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) have been observed in many cancers and may contribute to progression and metastasis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunohistochemical expression of uPA , uPAR , and PAI 1 in breast carcinoma . ^^^ We have used immunohistochemistry to examine three components of this system , ie , uPA , uPA receptor ( uPAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) , in a pilot study on 142 cases of breast carcinoma . ^^^ These results suggest that strong expression of uPA , uPAR , and PAI 1 in fibroblasts rather than in tumor cells have the most impact on the clinical behavior of breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To investigate whether the course of primary melanoma disease correlates with expression of the various components of the proteolytic plasminogen activation ( PA ) system , immunohistochemical stainings for activators of plasminogen ( tissue type ( tPA ) and urokinase type ( uPA ) ) , inhibitors of plasminogen activation ( type 1 ( PAI 1 ) and type 2 ( PAI 2 ) ) and the receptor for uPA ( uPAR ) were performed on 214 routinely processed melanoma lesions . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To investigate the prognostic significance of the plasminogen activation system in human chondrosarcoma , the immunohistochemical expression of urokinase type plasminogen activator ( uPA ) , urokinase type plasminogen activator receptor ( uPAR ) , plasminogen activator inhibitor , 1 ( PAI 1 ) and 2 ( PAI 2 ) were analyzed in 28 patients with chondrosarcoma . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : We compared the biological characteristics , that is , growth rate , motility , and invasive activity , of five ovarian cancer cell lines with the gene expression of various matrix proteases ( matrix metalloproteinase 1 [ MMP 1 ] , MMP 2 , MMP 9 , membrane type MMP type 1 [ MT 1 MMP ] , MT 2 MMP , MT 3 MMP , urokinase plasminogen activator [ uPA ] ) , their inhibitors ( tissue inhibitor of metalloproteinase type 1 [ TIMP 1 ] , TIMP 2 , plasminogen activator inhibitor type 1 , [ PAI 1 ] , and PAI 2 ) , and the potential transcriptional regulators E1AF and Ets 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : The expression of uPA , uPAR , the tissue type plasminogen activator , and plasminogen activator inhibitor ( PAI ) 1 and PAI 2 was investigated using reverse transcription followed by polymerase chain reaction and Western blotting . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , the role of the individual activators ( urokinase [ uPA ] and tissue plasminogen [ tPA ] activators ) and inhibitors ( plasminogen activator inhibitor [ PAI 1 ] ) of the fibrinolytic system in maintaining patency after coronary artery angioplasty and stenting is unclear . ^^^ Antigen and activity assays were performed for uPA , tPA , and PAI 1 . ^^^ At all time periods , including baseline , uPA antigen levels were significantly higher and PAI 1 antigen levels were significantly lower in patients with restenosis . ^^^ CONCLUSIONS : Plasma uPA antigen levels and PAI 1 antigen levels identify patients at increased risk for restenosis after percutaneous coronary revascularization . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We assessed plasminogen activator ( uPA and tPA ) and inhibitor ( PAI 1 ) expression in rat iliofemoral arteries after balloon injury using Western blot , enzyme activity , and quantitative reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrin autography showed that plasminogen dependent fibrinolytic activity occurred at M ( r ) of 110 kDa , which represents a complex of tPA with PAI 1 , and 65 and 55 kDa bands corresponding to tPA and uPA , respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This study was designed to investigate the relationship of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) to invasion and metastasis of hepatocellular carcinoma ( HCC ) . ^^^ The expression of uPA , uPAR , and PAI 1 in HCC was determined by immunohistochemistry , Northern blot , and an LCI D 20 nude mouse metastatic model of HCC . ^^^ The overexpression of uPA , uPAR , and PAI 1 was found in HCC , especially in the patients with portal cancer embolus , tumor invasion , and metastasis . ^^^ Immunohistochemistry results showed that the rate of positive staining of uPA , uPAR , and PAI 1 were higher in HCC than those in the control groups consisting of cancer adjacent tissue and normal liver tissue . ^^^ In those in which uPA , uPAR , and PAI 1 were all positive staining , stronger cancer invasiveness and higher mortality were found ( P < 0 . 05 vs . patients with all negative staining ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Deprivation of these two amino acids decreased the secretion of urokinase plasminogen activator ( uPA ) and tissue plasminogen activator ( tPA ) while plasminogen activator inhibitor ( PAI ) 1 and 2 were increased in these cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
That the urokinase plasminogen activator ( uPA ) was involved in the activation of procollagenase 1 was suggested by findings that the 120 kDa Fn fragment induced uPA coordinately with procollagenase 1 , and the activation of procollagenase 1 was dose dependently inhibited in the presence of plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Levels of tissue and urokinase plasminogen activator ( t PA and uPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and type 2 ( PAI 2 ) mRNA and protein were assessed by quantitative reverse transcriptase polymerase chain reaction ( Q RT PCR ) and ELISA , respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We studied disruption of the blood brain barrier ( BBB ) and changes in the vasculature after a brain stab wound in uPA deficient , uPA receptor deficient , and PA inhibitor 1 ( PAI 1 ) deficient mice . ^^^ The extravasation of immunoglobulin was greater in PAI 1 deficient mice ; less pronounced in uPA deficient mice ; similar to controls in uPA receptor deficient mice . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Concentrations of the fibrinolytic components tPA and urokinase plasminogen activator ( uPA ) , tPA activity and plasminogen activator inhibitor type 1 ( PAI 1 ) concentration were measured by enzyme linked immunoabsorbent assay . ^^^ However , neither uPA ( P = 0 . 29 ) nor PAI 1 ( P = 0 . 84 ) concentrations differed significantly in fluid compared with blood . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , and its inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) , are proposed to be prognostic factors in some cancers . ^^^ METHODS : To determine the prognostic value of the urokinase plasminogen activation system , contents of uPA , uPAR , and PAI 1 were measured in extracts of endometrial cancer tissue using ELISAs . uPA , uPAR , and PAI 1 levels were determined in 91 , 54 , and 92 extracts , respectively , and correlated with tumor histology , stage , grade , lymph node involvement , prevalence of metastasis , and recurrence as well as with estrogen ( ER ) , progesterone ( PR ) , epidermal growth factor ( EGFR ) receptor and HER 2 / neu contents . ^^^ CONCLUSION : Elevated uPA and PAI 1 levels appear to correlate with unfavorable prognosis in endometrial cancer . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Among the proteases involved in the tumor invasion process , components of the plasminogen activator system ( plasminogen activator type urokinase uPA , its membrane receptor uPAR and its two inhibitors PAI 1 and PAI 2 ) appear to define high risk patients in primary breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We examined the relationship between tumor tissue level of the complex formed of urokinase ( uPA ) and its type 1 inhibitor ( PAI 1 ) and survival of breast cancer patients . ^^^ Using a newly established ELISA , the levels of preformed uPA PAI 1 complex were measured in tumor tissue extracts and analyzed with respect to total uPA , total PAI 1 , and clinicopathological parameters , including survival . uPA PAI 1 complex comprised a minor , variable fraction of both total uPA and PAI 1 levels . ^^^ The tumor levels of complex , uPA , and PAI 1 were all associated with survival ; high complex levels predicted longer recurrence free survival ( P = 0 . 03 ) and overall survival [ OS ( P = 0 . 005 ) ] , whereas high uPA or PAI 1 levels significantly predicted shorter survival . ^^^ Additional studies are needed to understand the relationship of these parameters to cancer biology and to assess the clinical utility of the uPA PAI 1 complex . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
AIMS : To plasminogen activator system ( PAS ) consists of the plasminogen activators ( urokinase ( uPA ) and tissue type ( tPA ) plasminogen activators ) , the uPA receptor ( uPAR ) , and the plasminogen activator inhibitors ( PAI 1 and PAI 2 ) . ^^^ CONCLUSION : The involvement of the PAS and VEGF in colorectal cancer appears to be complex . uPA , uPAR , PAI 1 , and VEGF were upregulated in tumour tissue and this correlated with Dukes ' s staging and lymphatic invasion . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , after the incubation of PAI 1 with SP 40 , 40 at 37 degrees C for 1 h , PAI 1 could still form a complex with tissue plasminogen activator ( tPA ) , and it inhibited plasmin formation in the mixture of plasminogen and urine plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of tissue plasminogen activator ( tPA ) , urokinase ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) and inhibitor 2 ( PAI 2 ) in bile were measured by enzyme linked immunoassay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The effect of PAI 2 on papilloma formation did not appear to involve inhibition of the secreted protease urokinase type plasminogen activator ( uPA ) : PAI 2 accumulated predominantly in cells , and PAI 2 overexpression failed to alleviate a phenotype induced by uPA secretion , as demonstrated by a double transgenic strategy . ^^^ In addition , in situ hybridization revealed that uPA mRNA is not expressed concomitantly with PAI 2 in developing papillomas . ^^^ We conclude that overexpression of PAI 2 promotes the development and progression of epidermal papillomas in a manner that does not involve inhibition of its extracellular target protease , uPA , but appears to be related to an inhibition of apoptosis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : The aim of the study was to evaluate the prognostic significance of tumour and serum concentrations of urokinase type plasminogen activator ( uPA ) , its type 1 inhibitor ( PAI 1 ) and cathepsin D ( Cath D ) in patients with squamous cell carcinoma of the head and neck ( SCCHN ) . ^^^ PATIENTS AND METHODS : Determinations of uPA and PAI 1 were made using enzyme linked immunosorbent assays in tumour and serum samples of 47 and 32 / 47 patients , respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : Urokinase type plasminogen activator ( uPA ) and its inhibitor , plasminogen activator inhibitor ( PAI ) 1 , have been shown to be related to poor prognosis in a variety of malignant solid tumors . ^^^ Studies on the prognostic relevance of uPA and PAI 1 in ovarian cancer , however , have been inconclusive . ^^^ The current study tests the hypothesis that elevated expression of uPA and PAI 1 is associated with prognosis and disease progression . ^^^ EXPERIMENTAL DESIGN : uPA and PAI 1 were prospectively measured by quantitative ELISA in tumor samples from 103 ovarian cancer patients ( 82 primary invasive epithelial carcinomas , 9 low malignant potential tumors , and 12 recurrent ovarian carcinomas ) . ^^^ RESULTS : uPA but not PAI 1 levels were consistently associated with malignant progression , with levels increased from low malignant potential tumors to primary tumors ( uPA , P = 0 . 04 ; PAI 1 , P = 0 . 019 ) , from early to advanced disease stages ( uPA , P = 0 . 014 ; PAI 1 , P = 0 . 23 ) , and from primary to intra abdominal metastatic tumors ( uPA , P = 0 . 001 ; PAI 1 , P = 0 . 16 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , expression and selected activities of urokinase type plasminogen activator ( uPA ) , matrix metalloproteinases ( MMPs ) , their inhibitors ( plasminogen activator inhibitor 1 ( PAI 1 ) and tissue inhibitors of metalloproteinases ( TIMPs ) ) were examined in bovine oviducts by RT PCR , ribonuclease protection assay and activity assays . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MCs reacted with monoclonal antibodies to tryptase , chymase , and c kit / CD117 and stained positively for tissue type plasminogen activator ( tPA ) and urokinase receptor ( uPAR / CD87 ) but did not express detectable urokinase ( uPA ) or plasminogen activator inhibitors ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PSK also suppressed the expression of urokinase plasminogen activator ( uPA ) and uPA receptor but did not change plasminogen activator inhibitor 1 ( PAI 1 ) expression . ^^^ Western blot analysis showed that PSK reduced uPA protein expression but not PAI 1 expression in the both cell lines . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These clinical data have since been supported by experimental evidence that the concerted action of uPA , its cell surface receptor uPA R , and PAI 1 facilitates invasion and metastasis . ^^^ There is clinical evidence that high risk patients with elevated PAI 1 in their tumor benefit from adjuvant systemic therapy . uPA also has a strong prognostic impact in primary breast cancer . ^^^ In node negative breast cancer , risk group selection for adjuvant systemic therapy based on tumor levels of both PAI 1 and uPA is close to routine clinical use . ^^^ Novel therapeutic approaches targeting the PAI 1 / uPA interaction are already in pre clinical testing . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Proteolytic enzymes , like urokinase ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) , are involved in remodelling tissues during invasion and metastasis of tumor cells . ^^^ We used immunohistochemical staining to localize uPA and PAI 1 antigens and evaluate their expression , and the enzyme linked immunosorbent assay ( ELISA ) to measure their levels during the progression of endometrial carcinoma . ^^^ The results show that the levels of uPA and PAI 1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia . ^^^ We did not find any correlation between uPA and PAI 1 concentrations and the standard prognostic parameters for evaluating endometrial carcinoma . ^^^ In conclusion , this study demonstrates that in hyperplastic endometria and in endometrial carcinoma there is a progressive increase in expression of uPA and PAI 1 than in normal endometrial tissue . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Therefore , the expression of the matrix metalloproteinase ( MMP ) 2 and MMP 9 and of the serine protease urokinase type plasminogen activator ( uPA ) and its inhibitor plasminogen activator inhibitor type 1 ( PAI 1 ) in the progression of ovarian cancer was investigated . ^^^ In the same tissue extracts , antigen levels of uPA and its inhibitor PAI 1 were determined by ELISA . ^^^ Protein expression of pro MMP 2 ( 72 kDa ) and pro MMP 9 ( 92 kDa as well as antigen levels of uPA and PAI 1 were low in benign ovarian tumors but increased significantly from LMP tumors to advanced ovarian cancers . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : Recent studies suggest that HER 2 / neu specifically promotes the invasive capacity of tumor cells by up regulating secretion of the proteolytic enzyme , urokinase type plasminogen activator ( uPA ) , or its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) , in colon and gastric cancer . ^^^ It was the purpose of this study to : ( a ) evaluate the association between HER 2 / neu and uPA and PAI 1 expression in a large primary breast cancer cohort ; ( b ) perform the first multivariate analysis , including HER 2 / neu , uPA , and PAI 1 in breast cancer ; and ( c ) define the effect of HER 2 / neu overexpression on uPA and PAI 1 expression in breast cancer cells . ^^^ EXPERIMENTAL DESIGN : HER 2 / neu , uPA , and PAI 1 were measured as continuous variables by ELISA in primary breast cancer tissue extracts from 587 patients with clinical follow up and analyzed for correlations with clinical outcome . ^^^ Furthermore , a full length human HER 2 / neu cDNA was introduced into five human breast cancer cell lines to define the effects of HER 2 / neu overexpression on uPA and PAI 1 expression . ^^^ In addition , we tested whether HER 2 / neu antibodies could reverse any given alteration of uPA and PAI 1 levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
AIMS : Weak staining for urokinase plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , or plasminogen activator inhibitor 1 ( PAI 1 ) confined to crescents has been described in a few cases of severe crescentic glomerulonephritis . ^^^ METHODS AND RESULTS : We examined uPA , tPA and PAI 1 mRNA expression in 12 renal biopsies with crescentic glomerulonephritis , and in six control renal biopsies with no detectable abnormalities by RNA in situ hybridization . ^^^ The expressions of uPA , tPA and PAI 1 proteins were also assessed by immunofluorescence . ^^^ To better determine the cellular origin of uPA and PAI 1 transcripts , CD 68 protein was studied by immunohistochemistry on the same sections on which in situ hybridization had been performed . ^^^ In controls , there were very low level signals of uPA and PAI 1 mRNAs in a few glomerular epithelial cells ( GECs ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Several antibodies against the serine proteinase domain ( SPD ) were found to have overlapping epitopes composed of variable combinations of Arg 178 , Arg 179 , His 180 , Arg 181 , Tyr 209 , Lys 211 , and Asp 214 in the so called 37 loop and 60 loop , located near the active site and taking part in the binding of uPA to plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^ Besides inhibiting uPA catalysed plasminogen activation , all antibodies to SPD strongly delayed the binding of uPA to PAI 1 , decreasing the second order rate constant 15 to 6500 fold . ^^^ There was no correlation between the relative effects of the 37 loop and 60 loop substitutions on the second order rate constant and on the binding of the antibodies , indicating that the antibodies did not delay complex formation by blocking residues of specific importance for the uPA PAI 1 reaction , but rather by steric hindrance of the access of PAI 1 to the active site . ^^^ The affinity of the SPD antibodies for the uPA PAI 1 complex was only slightly lower than that for free uPA , indicating that the 37 loop and 60 loop are exposed in the complex . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : A balance between urokinase type plasminogen activator ( uPA ) and its main inhibitor type 1 ( PAI 1 ) appears to be important for cancer invasive behavior . ^^^ Since uPA / PAI 1 system seems to be regulated by transforming growth factor beta 1 ( TGFbeta 1 ) in different cell types , our aim was to investigate the relationship between the expression of the three genes and lymph node status in head and neck squamous cell carcinomas ( HNSCC ) at specific sites . ^^^ MATERIALS AND METHODS : uPA , PAI 1 , and TGFbeta 1 mRNAs were determined by Northern analysis in tumor , and paired normal mucosa samples were obtained from 91 operable HNSCC patients . ^^^ RESULTS : In oral cavity , excluding tongue , TGFbeta 1 , PAI 1 , and uPA mRNAs values were consistently lower in the normal tissues than in tumors . ^^^ In larynx tumors , TGFbeta 1 expression was increased , but no statistically significant differences were found for uPA or PAI 1 mRNAs as compared with normal tissues . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Enzyme immunoassay ( ELISA ) was used to estimate the levels of plasminogen activators of urokinase ( uPA ) and tissue ( tPA ) types and one of their inhibitors ( PAI 1 ) in the cytosolic fraction of the thyroid in 129 patients with malignant and benign tumors and various non cancer diseases of the gland . ^^^ Tumors from patients with thyroid cancer displayed the lowest levels of tPA and the highest levels of uPA and PAI 1 , while those from patients with benign thyroid diseases , including adenoma , had high concentrations of tPA and relatively low levels of uPA and PAI 1 in the tissue of the diseased organ . ^^^ At the same time , the lowest levels of uPA and PAI 1 were found in patients suffering from toxic goiter with and without adenomatosis . ^^^ In terms of uPA and PAI 1 levels , patients with nodular colloidal goiter were intermediate between those with toxic goiter and adenoma , on the one hand , and those with thyroid cancer , on the other . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Analysis of the proteolytic plasminogen activator system revealed that endostatin modulates the distribution of soluble and cell surface associated urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor , type 1 ( PAI 1 ) . ^^^ Casein zymographic and immunoprecipitation analyses indicated that endostatin exerts its effects by decreasing the levels of soluble uPA and PAI 1 and their complexes in a dose dependent manner . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To establish the necessary and sufficient components of the PA system [ PAI 1 , urokinase type PA ( uPA ) , or tissue type PA ( tPA ) , and plasminogen ( Plg ) ] for angiogenesis , we examined angiogenic competence of vascular explant cultures obtained from mice deficient in PAI 1 , tPA , uPA , and Plg . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Furthermore , adhesion to vitronectin and fibronectin was reduced by compounds that interfere with integrin function , such as EDTA , anti integrin antibodies , or by antibodies that interfere with the binding of pro uPA to uPAR , soluble uPAR , soluble vitronectin , phosphatidylinositol specific phospholipase C , as well as plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 ( plasminogen activator inhibitor 1 ) binds the urokinase type plasminogen activator ( uPA ) and causes its degradation via its receptor uPAR and low density lipoprotein receptor related protein ( LRP ) . ^^^ While both uPA and PAI 1 are chemoattractants , we find that a preformed uPA PAI 1 complex has no chemotactic activity and that PAI 1 inhibits uPA induced chemotaxis . ^^^ The inhibitory effect of PAI 1 on uPA dependent chemotaxis is reversed when uPAR internalization is inhibited by the 39 kDa receptor associated protein or by anti LRP antibodies . ^^^ Under the same conditions , the uPA PAI 1 complex is turned into a chemoattractant causing cytoskeleton reorganization and extracellular regulated kinase / mitogen activated protein kinases activation . ^^^ PAI 1 ( plasminogen activator inhibitor 1 ) binds the urokinase type plasminogen activator ( uPA ) and causes its degradation via its receptor uPAR and low density lipoprotein receptor related protein ( LRP ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Highly significant quantitative increases in urokinase PA ( uPA ) , urokinase receptor ( uPAR ) and plasminogen activator inhibitor 1 were detected in acute multiple sclerosis lesions ( P < 0 . 0001 ) and in uPAR in normal appearing white matter ( P < 0 . 0001 ) compared with control tissue . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , we characterized the production of fibrinolytic factors including tissue type plasminogen activator ( tPA ) , urokinase type PA ( uPA ) , and PAI 1 in the differentiation of preadipocytes , and examined the hormonal regulation of these fibrinolytic factors in mature adipocytes . ^^^ Insulin , IBMX , and dexamethasone significantly decreased both uPA and tPA production , and increased PAI 1 production . ^^^ Our results reveal that uPA is one of the markers for the differentiation of 3T3 L 1 cells and that insulin , IBMX , and dexamethasone are potent regulators of the fibrinolytic activity in differentiated 3T3 L 1 cells , reciprocally affecting PA and PAI 1 levels in them . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The Cyr 61 regulated genes fall into several groups known to participate in processes important for cutaneous wound healing , including : 1 ) angiogenesis and lymphogenesis ( VEGF A and VEGF C ) ; 2 ) inflammation ( interleukin 1beta ) ; 3 ) extracellular matrix remodeling ( MMP 1 , MMP 3 , TIMP 1 , uPA , and PAI 1 ) ; and 4 ) cell matrix interactions ( Col1alpha1 , Col1alpha2 , and integrins alpha ( 3 ) and alpha ( 5 ) ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Indeed in several tumour types , elevated levels of uPA , its receptor ( uPAR ) or its inhibitor plasminogen activator inhibitor 1 ( PAI 1 ) is associated with a poorer prognosis . ^^^ The aims were to assess whether the uPA , uPAR and / or PAI 1 correlates with angiogenic activity and could therefore be a useful objective clinical measure of tumour neovascularization ; and to clarify whether the poor outcome associated with high levels of the urokinase system is due to its association with angiogenesis . ^^^ The cytosolic levels of uPA , PAI 1 and uPAR were therefore measured by enzyme linked immunoabsorbent assay , together with tumour vascularity , in 136 well characterized invasive breast carcinomas . ^^^ There were significant relationships between uPA and uPAR ( Spearman r=0 . 37 , p < 0 . 0001 ) , uPA and PAI 1 ( Spearman r=0 . 19 , p=0 . 03 ) and between uPAR and PAI 1 ( Spearman r=0 . 23 p=0 . 01 ) . ^^^ A significant correlation was also observed between PAI 1 and vessel remodelling ( Spearman r=0 . 34 , p=0 . 04 ) , patient age ( p=0 . 01 ) , nodal status ( p=0 . 047 ) and tumour grade ( p=0 . 04 ) , but no association between tumour vascularity and PAI ( p=0 . 96 ) , uPA ( p=0 . 69 ) or uPAR ( p=0 . 81 ) was present . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Antibodies to PA 1 dose dependently , and significantly , inhibited the invasive and migratory potential of human HT 1080 fibrosarcoma cells , as did an antibody to uPA and the plasmin inhibitor aprotinin . ^^^ The non invasive human melanoma cell line , IF 6 , which does not express uPA , provided further confirmation of PAI 1 and uPA ' s role as , upon transfection with uPA , this cell line attained an invasive phenotype , which was again attenuated by MAI 12 . ^^^ Although antibodies to PAI 1 did not affect the adhesion of HT 1080 cells to vitronectin , the antibody to uPA reduced their attachment . ^^^ Furthermore melanoma cells transfected with a uPA variant , which had an impaired interaction with PAI 1 , were not invasive and had impaired binding to vitronectin . ^^^ These data also suggest that uPA and PAI 1 may co operate in the migratory process by respectively facilitating the attachment to , and subsequent detachment from , vitronectin in the extracellular matrix . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The components of the plasminogen activator system were measured , i . e . tissue plasminogen activator ( tPA ) , urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
After a median follow up time of 6 . 8 years , univariate analysis of patients with stage 1 2 disease ( n=188 ) showed that high u PA and high PAI 1 content was associated with a shorter progression free survival ( PFS ) , but at different cut off levels , uPA at the median ( P=0 . 003 ) , and PAI 1 at the 80th percentile ( P < 0 . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study we examined the relation of uPA ( urokinase plasminogen activator ) , uPAR ( uPA receptor ) and PAI 1 ( plasminogen activator inhibitor type 1 ) to the biological growth behavior of esophageal cancer , as well as their influence on survival in esophageal cancer . ^^^ MATERIALS and METHODS : The expression and distribution of uPA , uPAR and PAI 1 were analyzed by Northern blot analysis and immunostaining in 41 resected esophageal cancers and in normal esophagi . ^^^ RESULTS : Northern blot analysis revealed a 5 . 0 , 3 . 6 and 5 . 4 fold increase in uPA , uPAR , and PAI 1 mRNA levels in esophageal cancer , respectively , in comparison to normal controls ( p < 0 . 01 ) . ^^^ Statistical analysis revealed no differences in uPA , uPAR and PAI 1 immunoreactivity between well differentiated , moderately differentiated and poorly differentiated tumors . ^^^ CONCLUSION : Our data revealed that overexpression of uPA , uPAR and PAI 1 is often present in human esophageal carcinomas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
There is abundant evidence that the plasminogen activator ( PA ) system with its key components uPA ( urokinase type plasminogen activator ) , its cell surface receptor uPA R ( CD 87 ) and its inhibitor PAI 1 plays a key role in tumour invasion and metastasis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
There is ample information on the clinical role of biologic factors in female breast cancer : urokinase type plasminogen activator ( uPA ) , its receptor uPAR , its inhibitors PAI 1 and PAI 2 , cathepsin D and pS 2 protein . ^^^ We determined the cytosolic levels of oestrogen receptor ( ER ) , progesterone receptor ( PgR ) , cathepsin D , pS 2 protein , uPA , uPAR , PAI 1 and PAI 2 of the primary tumour tissues from 40 male breast cancer patients . ^^^ In male breast tumours the level of PgR was higher , those of uPA , PAI 1 , PAI 2 and cathepsin D lower . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The present study was undertaken to investigate the expression of the molecules of the PA system ( tPA , uPA , PAI 1 , uPAR , LRP ) , as well as several members of the MMP family and their inhibitors in the course of actively induced EAE in BALB / c mice . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Thrombin / antithrombin 3 complex ( TAT ) , soluble fibrin ( SF ) , total fibrinogen and fibrin degradation products ( TDP ) , plasminogen activator inhibitor type 1 ( PAI 1 ) , urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) were measured preoperatively , starting anesthesia , during surgery and postoperatively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
AIM : To determine the activity of glutathione ( GSH ) and concentrations of glutathione S transferases ( GST ) , urokinase type plasminogen activator ( uPA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) , and to evaluate their diagnostic and prognostic value and possible correlation with clinical and histopathological prognostic factors for ovarian carcinomas . ^^^ METHODS : The concentrations of GSH , uPA , PAI 1 , and activity of GST were analyzed in 35 tissue samples taken from 10 normal ovaries , 10 benign , 10 primary malignant , and 5 metastatic ovarian tumors . ^^^ The GSH level and GST activity were determined by spectrophotometric methods , and uPA and PAI 1 concentrations by ELISA commercial kits . ^^^ There were no statistical differences in uPA and PAI 1 concentrations between normal , benign , and malignant tumor samples . ^^^ Concentrations of GSH , uPA and PAI 1 , and activity of GST were independent from histopathological and clinical prognostic factors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
DRL performance in mice with deletion of tPA , uPA or PAI 1 genes . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary inhibitor of tPA and uPA activity , and is expressed in corresponding brain areas . ^^^ The current set of experiments were designed to investigate further the role of tPA and to extend our knowledge to uPA and PAI 1 , using mice with the respective genes deleted ( uPA / and PAI 1 / mice ) in the DRL 15 ' ' task . uPA / mice showed no disruption of DRL acquisition , but PAI 1 / mice showed a deficit similar to that seen in tPA / mice . ^^^ These data indicate that uPA deletion does not affect performance of a standard DRL 15 ' ' task , whereas deletion of PAI 1 has the same behavioural consequences in these tasks as deletion of tPA . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary inhibitor of tPA and uPA activity , and is expressed in corresponding brain areas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of tissue factor ( TF ) , the primary initiator of hemostasis ; urokinase type plasminogen activator ( uPA ) ; tissue type plasminogen activator ( tPA ) ; plasminogen activator inhibitor 1 ( PAI 1 ) as well as the potent matrix metalloprotease , MMP 3 was assessed . ^^^ It was observed , that RU 486 blocks and reverses progestin enhanced stromal cell TF protein and mRNA expression and PAI 1 protein and mRNA expression , whereas blocks and reverses progestin inhibited stromal cell uPA , tPA and MMP 3 protein and mRNA expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recent evidence confirms the independent prognostic value of VEGF , UPA and PAI 1 in women with early breast cancer and suggests that such parameters may have a role in selecting systemic therapy . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Components investigated were the fibrinolytic stimulator tissue plasminogen activator ( t PA ) , urokinase plasminogen activator ( uPA ) and the antagonist . plasminogen activator inhibitor type one ( PAI 1 ) . ^^^ RESULTS : Immediately after 8 h of total anoxia and reoxygenation with HBO 2 ( for 1 . 5 h ) , the mean ( SEM ) concentrations of t PA , PAI 1 and uPA were significantly increased compared to the other groups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Y box factor YB 1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER 2 , uPA and PAI 1 . ^^^ In our pilot study , we analyzed the clinical relevance of YB 1 expression in breast cancer ( n = 83 ) after a median follow up of 61 months and compared it with tumor biologic factors already used for clinical risk group discrimination , i . e . , HER 2 , urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ There was no significant correlation between YB 1 expression and either HER 2 expression or uPA and PAI 1 levels . ^^^ Risk group assessment achieved by YB 1 differed significantly from that by HER 2 or uPA / PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
On the other hand , high tumor tissue concentrations of urokinase plasminogen activator ( uPA ) , uPA receptor ( R ) and PAI 1 have more consistently been associated with poor histologic differentiation and poor prognosis . ^^^ The results were also compared with DNA ploidy status , S phase fraction , uPA and PAI 1 , which we reported in a previous study ( Fredstorp Lidebring et al . , Eur J Cancer 2001 ; in press ) . ^^^ A high PAI 2 level was associated with shorter progression free survival in univariate analysis and was an independent prognostic factor in bivariate analyses , which included PAI 1 , uPA and DNA ploidy status . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition to inhibiting serine proteases , mainly tissue type ( tPA ) and urokinase type ( uPA ) plasminogen activators , PAI 1 interacts with different components of the extracellular matrix , i . e . fibrin , heparin ( Hep ) and vitronectin ( Vn ) . ^^^ In contrast to other active PAI 1 mutants , the inhibitory properties of A 114 118 towards thrombin as well as uPA were significantly reduced in the presence of Hep . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , we used immunohistochemistry and in situ hybridization techniques to determine the localization of urokinase type ( u PA ) and tissue type ( t PA ) plasminogen activators , type 1 plasminogen activator inhibitor ( PAI 1 ) and membrane receptor for u PA ( uPA R ) antigen and their sites of synthesis in renal thrombotic microangiopathy ( N = 10 ) as compared to acute tubular necrosis ( N = 5 ) and normal human kidneys ( N = 7 ) . ^^^ We found an induction of PAI 1 and uPA R expression in glomeruli and in arterial walls in renal thrombotic microangiopathy . ^^^ In most case , local synthesis of PAI 1 and uPA R was confirmed by in situ hybridization with the corresponding cDNA probes . ^^^ In contrast , using similar techniques PAI 1 and uPA R antigens and messenger RNAs could not be detected in normal kidneys . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) system is a dynamic complex in which the membrane receptor uPAR binds uPA that binds the plasminogen activator inhibitor ( PAI ) 1 localized in the extracellular matrix , resulting in endocytosis of the whole complex by the low density lipoprotein receptor related protein ( LRP ) . ^^^ We previously reported a nonproteolytic role of the [ uPAR : uPA : PAI 1 : LRP ] complex operative in cell migration . ^^^ We showed that the uPA system and LRP are localized at filopodia of invasive cells , and that formation / internalization of the [ uPAR : uPA : PAI 1 : LRP ] complex is required for attachment and migration of cancer cells on plastic and on a PAI 1 coat . ^^^ Migration velocity , expression of the uPA system , use of the [ uPAR : uPA : PAI 1 : LRP ] complex to migrate , and promigratory effects of PAI 1 paralleled cancer cell invasiveness . ^^^ Phenotyping and functional analysis of invasive cancer cell subclones indicated that different cell subpopulations may use different strategies to migrate depending on both the environment and their expression of the uPA system , some of them taking advantage of abundant available PAI 1 . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : Urokinase type plasminogen activator ( uPA ) and its inhibitor ( PAI 1 ) play essential roles in tumor invasion and metastasis . ^^^ High levels of both uPA and PAI 1 are associated with poor prognosis in breast cancer patients . ^^^ To confirm the prognostic value of uPA and PAI 1 in primary breast cancer , we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer Receptor and Biomarker Group ( EORTC RBG ) . ^^^ Levels of uPA and PAI 1 in tumor tissue extracts were determined by different immunoassays ; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets . ^^^ Associations of ranks of uPA and PAI 1 levels with relapse free survival ( RFS ) and overall survival ( OS ) were analyzed by Cox multivariable regression analysis stratified by dataset , including the following traditional prognostic variables : age , menopausal status , lymph node status , tumor size , histologic grade , and steroid hormone receptor status . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Antibodies to both uPA and uPA receptor ( uPAR ) were shown to significantly inhibit cell invasion , as did the uPA inhibitors ( plasminogen activator inhibitor 1 [ PAI 1 ] , p aminobenzamidine [ PABN ] , aprotinin , and amiloride ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the plasmin dependent pathway , the expression of plasminogen activator inhibitor ( PAI 1 ) mRNA was continuously increased , while the expression of urokinase type plasminogen activator ( uPA ) mRNA was not increased . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
When negative PAI 1 conupared with positive urokinase type plasminogen activator ( uPA ) and positive uPA receptor ( uPAR ) . ^^^ The nambeigs invasion case increased , the difference was more significant than that in the group with negative PAI 1 , uPA and uPAR ( P = 0 . 039 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : A strong prognostic impact of urokinase type plasminogen activator ( uPA ) and its inhibitor and plasminogen activator inhibitor type 1 ( PAI 1 ) as individual factors is well established in breast cancer . ^^^ PATIENTS AND METHODS : uPA and PAI 1 levels were prospectively measured by enzyme linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer . ^^^ RESULTS : In the clinically important subgroup of node negative patients without adjuvant systemic therapy ( n = 269 ; median follow up , 60 months ) , the clinical value of testing both uPA and PAI 1 is demonstrated . ^^^ The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low risk group . uPA / PAI 1 is the strongest predictor of disease free survival and overall survival ; patients with high uPA / PAI 1 have an increased relapse risk ( P < . 001 ; relative risk , 4 . 8 ; 95 % confidence interval [ CI ] , 2 . 5 to 9 . 1 ) , in particular for early relapse . ^^^ Even within risk groups stratified by established criteria ( nodal or menopausal status , tumor size , grade , or steroid hormone receptors ) , uPA / PAI 1 provides significant risk group discrimination . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Levels of tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor ( PAI ) type 1 ( PAI 1 ) and type 2 ( PAI 2 ) , and tPA / PAI complex in tissue extracts were determinated by commercially available enzyme linked immunosorbent assay kits . ^^^ RESULTS : tPA was significantly reduced in peritonitis compared with normal peritoneum ( P < 0 . 001 ) , whereas it was found that the levels of PAI 1 , PAI 2 , uPA , and tPA / PAI complex in peritonitis were significantly higher than those in normal controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tissue plasminogen activator ( tPA ) and urokinase ( uPA ) are targets of plasminogen activator inhibitor 1 ( PAI 1 ) inhibition . ^^^ Activation of protein kinase A ( PKA ) , however , lowered PAI 1 secretion induced by uPA and tPA , as a result of an inhibition of the PKC pathway and inhibition of Raf , Mek and MAPK phosphorylations . ^^^ These multiple pathways utilized by uPA and tPA to modulate PAI 1 secretion might be involved in determining the proteolytic or antiproteolytic potential of the SMCs under different pathophysiological conditions . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Its antiinvasive action is due to an upregulation of tissue inhibitor of matrix metalloprotease 1 ( TIMP 1 ) and plasminogen activator inhibitor ( PAI 1 ) and a downregulation of urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The independent prognostic value of protease uPA and its inhibitor PAI 1 for survival in breast cancer patients is firmly established . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The aim of the present study was to determine the level of urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and plasminogen activator inhibitor type 2 ( PAI 2 ) in normal and malignant tissues of corpus uteri and to evaluate the possible correlation with clinical and histopathological prognostic factors . ^^^ UPA , PA 1 and PAI 2 were determined by the ELISA assay in tissue cytosol of matched pair samples from 27 patients with endometrial carcinoma . ^^^ Results show that significantly higher levels of these proteins were found in malignant than in normal tissue samples ( uPA : 1 . 266 versus 0 . 633 ng / mg protein , PAI 1 : 4 . 468 versus 1 . 958 ng / mg protein , and PAI 2 : 3 . 428 versus 0 . 483 ng / ml protein ) . ^^^ The levels of uPA and PAI 1 did not correlate with clinical staging or pathohistological grading . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cytosol of primary breast cancers from 217 women of predominantly Arab ethnicity were assayed for uPA , tPA , PAI 1 and a subset for ER , PR and pS 2 . ^^^ PAI 1 was related to uPA and both were inversely correlated with PR and pS 2 ( PAI 1 also to ER ) . ^^^ Women with high tumour uPA and PAI 1 , but not tPA , had shorter overall , and relapse free , survival . ^^^ However , uPA and PAI 1 were more prognostically informative than ER or PR and their usefulness may extend to delineation of patients likely to respond to adjuvant therapy . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The components of the PPS include the urokinase plasminogen activator ( uPA ) , its cell surface receptor urokinase plasminogen activator receptor ( uPAR ) , and its naturally occurring inhibitors , plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) . ^^^ Increases in tumor and serum levels of uPA , uPAR , and PAI 1 are associated with a worse prognosis in patients with colon cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Invasion and metastasis of solid tumors require tumor biologic factors that promote the dissolution of the surrounding tumor matrix and the basement membranes , and the serine protease urokinase type plasminogen activator ( uPA ) and its inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) , play major roles in these invasive processes . ^^^ Our laboratory and others have reported that determinations by enzyme linked immunosorbent assay ( ELISA ) of uPA and PAI 1 concentrations in tumor tissue extracts reliably separate patients with node negative breast cancer at very low risk of relapse even without chemotherapy from high risk patients who urgently need intensive effective treatment in order to reduce increased mortality . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here , the authors investigated how PAF affects the expression of PAI 1 , TIMP 1 and 2 relative to that of uPA , MMP 1 , and 9 in rabbit corneal epithelial cells . ^^^ PAF produced a 20 fold increase in the gene expression of PAI 1 at 8 hr , while similar fold increases in uPA mRNA expression occurred at 2 hr . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunohistochemical expression of uPA , PAI 1 , cathepsin D and apoptotic cells in ductal carcinoma in situ of the breast . ^^^ We chose urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and Cathepsin D as invasive markers , and Ki 67 and C erbB 2 oncoproteins as proliferative factors for our study . ^^^ METHODS : We used immunohistochemical methods to investigate the expression of uPA , PAI 1 , Cathepsin D , Ki 67 , C erbB 2 and ssDNA ( single stranded DNA for apoptotic cells ) in 20 cases of DCIS . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Paradoxically , high levels of plasminogen activator inhibitor 1 ( PAI 1 ) , an endogenous inhibitor of uPA , also predict for aggressive disease . ^^^ Recently , the prognostic impact of both uPA and PAI 1 in axillary node negative breast cancer was confirmed using two different Level 1 Evidence studies , i . e . in both a randomized prospective trial and a pooled analysis . ^^^ Therefore , uPA and PAI 1 appear to have fulfilled all the criteria for the routine assessment of prognosis in newly diagnosed breast cancer patients . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Adhesion molecules ( E cadherin , catenins , serum intercellular adhesion molecule 1 , CD 44 variants ) , proteinases involved in the degradation of extracellular matrix ( MMP 2 , MMP 9 , uPA , uPAR , PAI ) , as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC , and are related to prognosis and therapeutic outcomes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Since anti invasive effects of TGF beta in the normal EVT cells were shown to be mediated in part by plasminogen activator inhibitor 1 ( PAI 1 ) and urokinase type plasminogen activator ( uPA ) , we compared the expression of PAI 1 and uPA in the normal EVT , JAR , and JAR smad3 / c cells in the presence or absence of TGF beta 1 . ^^^ The basal levels of PAI 1 mRNA and secreted PAI 1 and uPA proteins were found to be very low in JAR and JAR smad3 / c cells , as compared to the normal EVT cells . ^^^ However , TGF beta 1 upregulated PAI 1 and downregulated uPA in JAR smad3 / c cells , but not in JAR cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Northern blot analysis demonstrated that genes encoding urokinase type plasminogen activator ( uPA ) , urokinase type plasminogen activator receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , tissue inhibitor of metalloproteinases ( TIMP 1 ) and c myc were up regulated in response to hyaluronan . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , its inhibitors ( PAI 1 and PAI 2 ) , and its receptor ( uPAR ) play a key role in tumor invasion and metastasis . ^^^ This study was designed to evaluate the prognostic impact of uPA , PAI 1 , PAI 2 , and uPAR and the combination of these factors in a group of 460 primary breast cancer patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
After 48hr mRNA expression of MMP 1 , MMP 3 , TIMP 1 , uPA , tPA and PAI 1 was analyzed by RT PCR ELISA . ^^^ Both drugs inhibited the IL 1 induced mRNA expression of tPA , whereas expression of uPA was only mildly reduced by PSGAG , which also induced PAI 1 above IL 1 stimulated levels . ^^^ In this study we determined the in vitro effects of polysulfated glycosaminoglycan ( PSGAG ) and the glucocorticoid triamcinolone acetonid ( TA ) on the IL 1 altered expression and activity of matrix metalloproteinases ( MMP 1 , MMP 3 ) , tissue inhibitor of metalloproteinases 1 , the plasminogen activators tPA and uPA and plasminogen activator inhibitor 1 by articular chondrocytes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Human breast adenocarcinoma cell lines promote angiogenesis by providing cells with uPA PAI 1 and by enhancing their expression . ^^^ During angiogenesis , endothelial cells use uPA and PAI 1 to migrate and degrade the basement membrane surrounding capillary blood vessels . ^^^ Within a short incubation period ( 30 min ) with both CM , an increase of uPA , PAI 1 and uPA PAI 1 complex was detected in endothelial cell layer as assessed by casein zymography , ELISA and uPA immunostaining . ^^^ After 2 hr of incubation , the CM from both tumor cells upregulated uPA and PAI 1 mRNA levels in endothelial cells in a time dependent manner . ^^^ Our data demonstrate that the interactions occurring between breast tumor cells and endothelial cells can modulate tumor angiogenesis at least by two mechanisms : an increase of uPA and PAI 1 cell surface binding and of their expression by endothelial cells . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TCDD induced the early appearance of ovarian plasminogen activator inhibitor type 1 ( PAI 1 ) , plasminogen activator inhibitor type 2 ( PAI 2 ) , urokinase plasminogen activator ( uPA ) , and tissue plasminogen activator ( tPA ) at 24h after dosing when compared with controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Paradoxically , high concentrations of plasminogen activator inhibitor ( PAI 1 ) , an endogenous inhibitor of uPA , also correlate with poor prognosis in patients with breast cancer , including the subgroup with node negative disease . ^^^ The prognostic value of uPA / PAI 1 in axillary node negative breast cancer patients was recently confirmed in both a prospective randomized trial and a pooled analysis , i . e . , two different level 1 evidence ( LOE 1 ) studies . ^^^ CONCLUSIONS : uPA and PAI 1 are among the first biological prognostic factors to have their clinical value validated using LOE 1 evidence studies . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Quantitative real time reverse transcription PCR ( RT PCR ) assays were developed to quantify urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) , and tissue metalloproteinase inhibitor type 1 ( TIMP 1 ) mRNA in 54 breast cancer tissues . ^^^ PAI 1 , uPA , and TIMP 1 mRNA and antigen concentrations and PAI 1 and uPA functional concentrations increased with tumor severity ; the increase was statistically significant for PAI 1 , uPA , and TIMP 1 mRNA and antigen concentrations and for uPA functional concentrations . ^^^ Node positive patients showed significantly higher PAI 1 , uPA , and TIMP 1 mRNA and antigen concentrations than those who were node negative . ^^^ CONCLUSIONS : Quantitative real time RT PCR is a highly sensitive , reproducible , and fast method for measuring gene expression of PAI 1 , uPA , and TIMP 1 in breast cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We investigated the effects of low density lipoprotein ( LDL ) on PA inhibitor 1 ( PAI 1 ) , urokinase type PA ( uPA ) , and tissue type PA ( tPA ) in relationship to protein kinase C ( PKC ) in cultured human mesangial cells ( HMC ) . ^^^ LDL downregulated 2 . 4 kb PAI 1 , uPA , and tPA mRNA expression within 6 h of incubation with HMC . ^^^ On the other hand , after 12 48 h , LDL treated cells showed a significant increase in PAI 1 , tPA , and uPA mRNA levels . ^^^ The stimulatory effects of LDL on PAI 1 , tPA , and uPA gene regulation in HMC were blocked by the inhibition of PKC using GF 109203X 12 h after treatment with LDL or downregulation of PKC using phorbol myristate acetate . ^^^ In summary , LDL regulates PAI 1 , uPA , and tPA in biphasic patterns in HMC , and the upregulation of PAI 1 , uPA , and tPA after long term LDL exposure seems to be mediated by a delayed PKC activation associated with an increased PA inhibitory activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activator system , including urokinase type plasminogen activator ( uPA ) and type 1 plasminogen activator inhibitor ( PAI 1 ) , plays an important role in repair of the peritoneum damaged by several types of peritonitis . ^^^ We investigated and compared the expression of uPA and PAI 1 in the peritoneum of cancer patients with and without PD . ^^^ The presence or absence of cancer cells in the peritoneal tissues was confirmed by both hematoxylin eosin staining and reverse transcriptase polymerase chain reaction ( RT PCR ) detection of carcinoembryonic antigen ( CEA ) mRNA . uPA and PAI 1 mRNA expression in these peritoneal tissues was determined by RT PCR and the proteins were localized immunohistochemically . ^^^ RESULTS : uPA mRNA was expressed in the cancer cell positive peritoneum from 9 of the 11 ( 81 . 8 % ) patients with PD ; PAI 1 mRNA was expressed in the peritoneal tissue from 10 of ( 91 . 9 % ) these patients . ^^^ Either uPA or PAI 1 mRNA was expressed in the cancer cell negative peritoneum from 8 ( 72 . 7 % ) of the 11 patients with PD , whereas uPA mRNA was expressed in none of the peritoneal tissues from the 24 patients without PD and PAI 1 mRNA was expressed in specimens from 4 ( 16 . 7 % ) of these patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Ligands that regulate the interaction of uPA with LRP , such as PAI 1 or the PAI 1 derived peptide ( EEIIMD ) , abolished the vasoactivity of tcuPA in vitro and in vivo . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The strong prognostic impact of the two invasion factors urokinase type plasminogen activator ( uPA ) and its inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) , in breast cancer has recently been validated at level 1 evidence . ^^^ This article considers the predictive impact of uPA / PAI 1 on response to adjuvant chemo and endocrine therapy in 3424 primary breast cancer patients from two different data sets . uPA and PAI 1 antigen levels were measured by ELISA in primary tumor tissue extracts . ^^^ After a median follow up of 83 months , uPA / PAI 1 has a significant impact on disease free survival in Cox multivariate analysis ( P < 0 . 001 ; hazard ratio , 2 . 0 ; 95 % confidence interval , 1 . 8 2 . 3 ) . ^^^ Patients with high uPA / PAI 1 levels benefit more strongly from adjuvant chemotherapy than those with low levels . ^^^ This effect is seen as a significant interaction between chemotherapy and uPA / PAI 1 for the entire collective ( P < 0 . 003 ; hazard ratio , 0 . 68 ; 95 % confidence interval , 0 . 53 0 . 88 ) and separately within nodal subgroups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We found that mLRP1B4 and urokinase plasminogen activator receptor ( uPAR ) form immunoprecipitable complexes on the cell surface in the presence of complexes of uPA and its inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Expression of mLRP1B4 , or an mLRP 4 mutant deficient in endocytosis , leads to an accumulation of uPAR at the cell surface and increased cell associated uPA and PAI 1 when compared with cells expressing mLRP 4 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Invasion factors urokinase type plasminogen activator ( uPA ) and its plasminogen activator inhibitor ( PAI 1 ) are the only novel tumor biological prognostic factors validated at the highest level of evidence with regard to their clinical utility in breast cancer . ^^^ Numerous studies showed that patients with low levels of uPA and PAI 1 have a significantly better survival than patients with high levels of either factor . ^^^ The particular combination of both factors , uPA / PAI 1 ( both low vs . either or both factors high ) , outperforms the single factors as well as other traditional prognostic factors with regard to risk group assessment , particularly in node negative breast cancer . ^^^ Node negative breast cancer patients with low levels of uPA and PAI 1 have a very good prognosis and , as such , may be candidates for being spared the burden of adjuvant chemotherapy . ^^^ In contrast , node negative patients with high uPA / PAI 1 are at a substantially increased risk of relapse , comparable to that of patients with > or = 3 involved axillary lymph nodes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The prognostic biomarkers chosen for comparison represented surrogate measures of tumor : ( 1 ) . proliferation , growth and genetic instability ( mitotic and apoptotic indices , Ki 67 / MIB 1 positivity , nuclear grade , p 53 positivity ) , ( 2 ) . endocrine dependence ( estrogen receptor ( ER ) , progesterone receptors ( PR ) , pS 2 , Bcl 2 ) , ( 3 ) . growth factor receptor dependence ( ErbB 2 , EGFR / ErbB1 ) , and ( 4 ) . angiogenic , invasive and proteolytic potential ( uPA , PAI 1 , Cathepsin D , VEGF ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition to aspartyl and cysteineproteinases , serine proteinases including the plasminogen activator system ( uPA , uPAR , tPA , PAI 1 and PAI 2 ) and matrix metalloproteinases ( MMPs ) with their tissue inhibitors ( TIMPs ) play an essential role in these processes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Its major components are urokinase ( uPA ) and tissue type plasminogen activator ( tPA ) , plasminogen activation inhibitor type 1 and 2 ( PAI 1 and PAI 2 ) and a receptor for urokinase ( uPAR ) . ^^^ Spitz naevi had melanocytic positivity for uPA in 0 % ( 0 / 36 ) , tPA in 30 % ( 6 / 20 ) , PAI 1 in 10 % ( 3 / 35 ) , PAI 2 in 40 % ( 8 / 21 ) and uPAR in 60 % ( 13 / 21 ) of cases . ^^^ This was much ( for most components significantly ) less than the proportion of primary melanomas with tumour cell positivity , which was 30 % ( 11 / 38 ) for uPA , 80 % ( 19 / 24 ) for tPA , 75 % ( 28 / 38 ) for PAI 1 , 80 % ( 19 / 24 ) for PAI 2 and 80 % ( 19 / 24 ) for uPAR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , we describe an assay for the assessment of components of the plasminogen activation system ( uPA , tPA and PAI 1 , and their complexes ) in blood which is not susceptible to interference by heterophilic antibodies . ^^^ The assay is compared to our earlier reported ELISA for measuring uPA , tPA and PAI 1 components in tumor tissue extracts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , the antigen levels of urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 , and their immunohistochemical staining were compared in paired colorectal tumor ( n = 64 ) and background colon tissue of the same patients with clinical and pathological staging . ^^^ The antigen levels , measured with an ELISA method , were found to be significantly higher in cancer tissue ( mean 1 . 92 ng / mg protein for uPA and 7 . 08 for PAI 1 ) than in corresponding normal mucosa ( 0 . 29 ng / mg protein for uPA and 1 . 11 ng / mg protein for PAI 1 ) . ^^^ There was a positive correlation between uPA and PAI 1 antigen levels and clinicopathological parameters such as grade ( p < 0 . 001 and p = 0 . 01 , respectively ) , while for Dukes ' stage , only PAI 1 correlated positively ( p = 0 . 018 ) . ^^^ Nodal status correlated positively with uPA but not with PAI 1 antigen levels . ^^^ The degree of staining was associated with grade , Dukes ' stage and nodal status for uPA ( p < 0 . 001 , p = 0 . 002 , p < 0 . 001 , respectively ) and only with grade for PAI 1 ( p = 0 . 007 ) . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We evaluated the concentration and activities of tPA , uPA and PAI 1 in plasma from kidney allograft recipients . ^^^ The results of our study suggest a stimulatory effect of CsA on tPA and PAI 1 plasma activities as well as on uPA Ant concentration , while prednisone in turn seems to enhance PAI 1 activity in plasma and decrease uPA expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : To determine the in vitro effects of several nonsteroidal antiinflammatory drugs on the IL 1 altered expression and activity of tPA , uPA and PAI 1 by articular chondrocytes . ^^^ Expression of mRNA for the plasminogen activators ( uPA and tPA ) and their inhibitor ( PAI 1 ) were analyzed by RT PCR ELISA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : The fibrinolytic activities of conditioned medium and cell lysates from human glioma cell lines , A 172 , T98G , U 87 and TM 1 were studied by fibrin plate zymography . mRNA expression of tissue plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitors ( PAI 1 , PAI 2 ) was measured by Northern blot analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here , we show that oncostatin M ( OSM ) and interleukin 1 ( IL 1 ) regulate the expression of plasminogen activator inhibitor 1 ( PAI 1 ) and urokinase type plasminogen activator ( uPA ) in human astrocytes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In our study , we have studied the effects of CD 44 stimulation by ligation with HA upon the expression of matrix metalloproteinases ( MMPs ) 2 and 9 as well as urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and its inhibitor ( PAI 1 ) and the subsequent induction of invasion of human chondrosarcoma cell line HCS 2 / 8 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : The expression of uPA and PAI 1 as parameters of tumour associated proteolysis has been implicated in the process of tumour cell invasion and the metastatic process . ^^^ METHODS : Quantitative levels for uPA ( n = 114 ) and PAI 1 ( n = 103 ) were researched in operatively treated , surgically staged squamous cell cancer of the uterine cervix , using an ELISA technique . ^^^ Multivariate analysis , including nodal status , tumour stage , lymphovascular space involvement and grading failed to demonstrate any prognostic impact of uPA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumor tissues from 71 patients with CRC were assayed to determine the antigen levels of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor 1 and 2 ( PAI 1 and PAI 2 ) , as well as immunohistochemical expression of VEGF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To test the hypothesis that during wounding , exposed collagen , the most abundant ECM molecule in the skin , regulates keratinocyte PA and PAI gene expression , we utilized an in vitro model in which activated keratinocytes were cultured in dishes coated with collagen or other ECM substrates . tPA , uPA , and PAI 1 mRNA and enzymatic activity were detected when activated keratinocytes attached to fibronectin , vitronectin , collagen 4 , and RGD peptide . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : CSF and serum concentrations of urokinase plasminogen activator ( urokinase [ uPA ] ) , uPA receptor ( uPAR ) , and PA inhibitor 1 ( PAI 1 ) were quantified by ELISA in 12 patients with bacterial meningitis , control patients ( n = 10 ) with noninflammatory neurologic diseases , and 10 patients with Guillain Barr syndrome ( GBS ) , a disease in which blood CSF barrier disruption occurs without CSF pleocytosis . ^^^ The serum of patients with bacterial meningitis showed elevated protein levels of uPA , but not uPAR or PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
DNA synthesis was assessed by measuring the incorporation of [ 3H ] thymidine into cellular DNA fraction . tPA , uPA and type 1 plasminogen activator inhibitor ( PAI 1 ) gene expressions were measured by Northern blotting . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The serpin plasminogen activator inhibitor type 1 ( PAI 1 ) , as the primary physiological inhibitor of both urokinase type ( uPA ) and tissue type ( tPA ) plasminogen activator , plays an important role in the regulation of the fibrinolytic system as well as in extracellular remodeling in both physiological and pathophysiological processes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We hypothesized that the relative balance between urokinase type plasminogen activator ( uPA ) and PAI 1 expression in favor of uPA prevents scarring in early fetal skin wounds , whereas a change in favor of PAI 1 in late gestation results in wound scarring . ^^^ To evaluate uPA and PAI 1 expression , 1 mm skin wounds were made in E14 . 5 and E 18 mice and harvested 24 , 48 , or 96 hours postwounding . ^^^ Normal skin and skin wounds were evaluated for uPA , PAI 1 , and collagen expression . ^^^ We showed that in normal skin uPA level is higher in E14 . 5 than in E 18 mice , while PAI 1 is lower in E14 . 5 than in E 18 mice . ^^^ After wounding , E14 . 5 wounds show a moderate increase in uPA and a minimal increase in PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The regulated expression of the urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor ( PAI 1 ) is believed to modulate the invasive capacity of human trophoblastic cells in vitro and in vivo . ^^^ To date , the factors capable of regulating the expression of uPA and PAI 1 in these cells remain poorly characterized . ^^^ In these studies , we have examined the ability of the classical mammalian GnRH 1 and the second form of GnRH ( GnRH 2 ) to regulate uPA and PAI 1 mRNA and protein expression levels in primary cultures of human extravillous cytotrophoblasts using quantitative competitive PCR and ELISA , respectively . ^^^ Both GnRH 1 and 2 increased uPA and concomitantly decreased PAI 1 mRNA and protein expression levels in our extravillous cytotrophoblast cultures in a dose and time dependent manner . ^^^ Cetrorelix , a peptide GnRH antagonist specific for the GnRH 1 receptor , was capable of inhibiting the regulatory effects of GnRH 1 , but not GnRH 2 on uPA and PAI 1 expression levels in primary cell cultures . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We report here the following . 1 ) The human ovarian cancer cell line HRA produced secreted and cell associated urokinase type PA ( uPA ) and PA inhibitor type 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : Trophoblast proteases , matrix metalloproteases ( MMP 2 , MMP 9 ) , membrane type matrix metalloproteases ( MT MMP 1 & 2 ) and urokinase type plasminogen activator ( uPA ) were found to be up regulated by IL 1beta while the protease inhibitors , tissue inhibitor of metalloproteases ( TIMP 1 & 2 ) and plasminogen activator inhibitors ( PAI 1 & 2 ) to be up regulated by TGF beta 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : The roles of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) in the formation of macroscopic types and invasion were investigated . ^^^ MATERIALS AND METHODS : A total of 40 surgically resected esophageal carcinoma tissues were immunohistochemically stained , and the expression of uPA , PAI 1 and the uPA / PAI 1 ratio , were evaluated . ^^^ RESULTS : The expression of uPA was significantly stronger in the macroscopically infiltrative type ( n = 20 : p = 0 . 0027 ) , whereas PAI 1 was significantly stronger in the localized type ( n = 20 : p = 0 . 0005 ) . ^^^ The uPA / PAI 1 ratio was significantly higher in the infiltrative type ( p < 0 . 0001 ) . ^^^ CONCLUSION : The results demonstrated that uPA and PAI 1 play important roles in invasion and formation of macroscopic types of esophageal carcinoma . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Prognostic value of uPA , PAI 1 and PAI 2 mRNA expression in primary breast cancer . ^^^ BACKGROUND : The prognostic value of uPA , PAI 1 and PAI 2 mRNA expression was studied in a retrospective series of 130 primary breast cancer patients ( median follow up 8 . 1 years ) . ^^^ MATERIALS AND METHODS : UPA , PAI 1 and PAI 2 mRNA were quantified by means of real time quantitative RT PCR . ^^^ The mRNA expression of uPA , PAI 1 and PAI 2 was significantly correlated with one another . ^^^ Higher uPA and PAI 1 mRNA values were significantly associated with shorter disease free survival ( DFS ) ( p = 0 . 002 ; p = 0 . 03 , respectively ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have chosen plasminogen activator inhibitor ( s ) type 1 ( PAI 1 ) , which selectively inhibits the urokinase plasminogen activator ( uPA ) . ^^^ Novel PAI 1 were fully functional against uPA and showed activity in the in vitro model of angiogenesis , e . g . , in the inhibition of sprout formation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Besides degrading of matrix proteins , PMN E has been shown to be able to cleave and inactivate plasminogen activator inhibitor 1 ( PAI 1 ) , the main inhibitor of uPA , and alpha 2 antiplasmin , the natural inhibitor of plasmin , thus enabling an uncontrolled matrix degradation by the fibrinolytic enzymes . ^^^ Levels of complexed PMN E have been correlated with the lengths of metastasis free survival ( MFS ) , relapse free survival , and overall survival , and a comparison was made with data previously obtained for uPA and PAI 1 . ^^^ PMN E was an independent prognostic factor for MFS even in the multivariate analysis including the traditional clinical prognostic factors and the strong established biochemical prognostic factors uPA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Changes in the expression of urokinase type PA ( uPA ) , uPA receptor , and PAI 1 mRNA in BAEC after treatment with Rb 2 were analyzed by Northern blot . ^^^ Rb 2 greatly or moderately increased the amount of urokinase type PA ( uPA ) or its inhibitor ( PAI 1 ) , present in the culture medium , whereas saponin did not influence mRNA levels of uPA , its surface receptor , and PAI 1 , suggesting that Rb 2 may stimulate the secretion of uPA without enhancing its gene expression . ^^^ Rb 2 may stimulate the secretion of uPA without enhancing the gene expression of uPA , uPA receptor ( uPAR ) , and PAI 1 . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Accumulation of uPA PAI 1 complexes inside the tumour cells is associated with axillary nodal invasion in progesterone receptor positive early breast cancer . ^^^ Both urokinase like plasminogen activator ( uPA ) and its inhibitor plasminogen activator inhibitor ( PAI 1 ) , as well as uPA PAI 1 complexes , have been identified as important prognostic factors in breast cancer . ^^^ Using this technique , we have studied a series of 212 early ( pT 1 ) unifocal breast cancers and have correlated the expression of uPA PAI 1 complexes , together with other clinical and biological features ( histologic variety , histologic and nuclear grade , hormone receptors , Ki 67 labelling index , c erb B 2 , p 53 and CD44std expression ) with or without the occurrence of axillary node invasion . ^^^ In a logistic regression model , looking for associations with axillary metastasis , we found a statistically significant interaction between the presence of uPA PAI 1 complexes and progesterone receptor positivity ( P=0 . 04 ) . ^^^ A final model showed that the presence of uPA PAI 1 complexes was a determinant factor for axillary metastasis among women carrying tumours expressing progesterone receptors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of PAI 1 and its target proteinase uPA in tumour extracts were analysed by ELISA . ^^^ The Chalkley count was not correlated with the levels of uPA or PAI 1 . ^^^ High values of uPA , PAI 1 , and Chalkley count were all significantly correlated with a shorter recurrence free survival and overall survival . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Stromal cells also contribute to breast cancer growth and metastasis through the production of extracellular matrix ( ECM ) modifiers such as urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , its inhibitors ( PAI 1 and PAI 2 ) , matrix metalloproteinases ( MMPs ) , and growth factors , including the fibroblast and insulin like growth factors ( FGF ' s and IGF ' s ) . ^^^ We furthermore demonstrate in one tumour derived fibroblast strain that the increases in uPA and PAI 1 mRNA and MMP 2 protein production are inversely related to the telomere length . ^^^ Artificially increasing telomere length in this fibroblast strain by expressing human telomerase reverse transcriptase ( hTERT ) prevented senescence and resulted in late passage cultures with early passage uPA , PAI 1 and MMP 2 levels . ^^^ Our results show that aging accompanied by telomere loss induces PAI 1 and FGF 1 mRNA expression in all breast fibroblast strains , increases uPA and decreases IGF 1 mRNA expression in a subset , and increases MMP 2 protein expression only in tumour derived breast fibroblasts . ^^^ These age induced levels of PAI 1 , FGF 1 , uPA and MMP 2 in stromal breast fibroblast could contribute to breast cancer progression . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Moreover , using cells deficient for uPA receptor ( uPAR ) we have demonstrated that the inhibition of PAI 1 on insulin signaling is independent of uPAR VN binding . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We provide evidence that plasminogen activator inhibitor ( PAI ) 1 can detach cells by disrupting uPAR VN and integrin VN interactions and that it does so by binding to the uPA present in uPA uPAR integrin complexes on the cell surface . ^^^ Immunoprecipitation and subcellular fractionation experiments reveal that PAI 1 treatment triggers deactivation and disengagement of uPA uPAR integrin complexes and their endocytic clearance by the low density lipoprotein receptor related protein . ^^^ Transfection experiments demonstrate that efficient cell detachment by PAI 1 requires an excess of matrix engaged uPA uPAR integrin complexes over free engaged integrins and that changes in this ratio alter the efficacy of PAI 1 . ^^^ Together , these results suggest a VN independent , uPA uPAR dependent mechanism by which PAI 1 induces cell detachment . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Protein expression of the PAS , including urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , plasminogen ( Plg ) , and plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) , was determined in the colonic tissue samples of 56 patients with resected primary CRC by quantitative immunohistochemistry and correlated with clinicopathological parameters and patient outcome . ^^^ RESULTS : Overexpression of uPA ( t test , P < 0 . 001 ) , uPAR ( P < 0 . 001 ) and PAI 1 ( P = 0 . 031 ) was significantly associated with liver metastatic CRC tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have investigated whether there are any differences in the release of urokinase plasminogen activator ( uPA ) and its inhibitor ( PAI 1 ) from cultured endometrial and endometriotic stromal cells , and whether the release is regulated by epidermal growth factor ( EGF ) or transforming growth factor beta 1 ( TGFbeta 1 ) . ^^^ Stromal cells from all three types of tissues released uPA and PAI 1 , but the soluble receptor of uPA was not measurable in any group . ^^^ The basal release of uPA and PAI 1 from endometriotic cells was higher than from endometrial cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Invasion factors uPA / PAI 1 and HER 2 status provide independent and complementary information on patient outcome in node negative breast cancer . ^^^ PURPOSE : The independent clinical relevance of invasion factors urokinase type plasminogen activator ( uPA ) / PAI 1 and HER 2 status was evaluated in lymph node negative breast cancer patients ( N = 118 ) without adjuvant systemic therapy after long term follow up of more than 10 years ( median , 126 months ) . ^^^ PATIENTS AND METHODS : Levels of uPA and its inhibitor PAI 1 were prospectively measured by enzyme linked immunosorbent assay in primary tumor tissue extracts . ^^^ RESULTS : uPA / PAI 1 was high ( either one or both factors were high ) in 44 % of the tumors . ^^^ In a multivariate analysis of established and tumor biologic prognostic factors , uPA / PAI 1 was the only independent prognostic factor for disease free survival ( [ DFS ] ; P < . 001 ; relative risk [ RR ] , 8 . 3 ; 95 % confidence interval [ CI ] , 3 . 4 to 20 . 4 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen / plasmin system , urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , and its inhibitor ( PAI 1 ) , influence extracellular proteolysis and cell migration in lung injury or neoplasia . ^^^ In this study , we sought to determine whether tcuPA ( two chain uPA ) alters expression of its major inhibitor PAI 1 in lung epithelial cells . ^^^ Inactivation of the catalytic activity of tcuPA had little effect on PAI 1 induction and the activity of the isolated amino terminal fragment was comparable with full length single or two chain uPA . ^^^ In contrast , deletion of either the uPA receptor binding growth factor domain or kringle domain ( kringle ) from full length single chain uPA markedly attenuated the induction of PAI 1 . ^^^ Induction of PAI 1 by exposure of lung epithelial cells to uPA is a newly recognized pathway by which PAI 1 could regulate local fibrinolysis and urokinase dependent cellular responses in the setting of lung inflammation or neoplasia . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Newly described pathways by which lung epithelial cells regulate expression of uPA , its receptor uPAR , and PAI 1 at the posttranscriptional level have been identified . ^^^ The regulatory mechanisms seem to involve multiple protein mRNA interactions , and the phosphorylation state of the proteins appears to determine whether complex formation of , or dissociation from , the regulatory sequences occurs . uPA is capable of inducing its own expression in lung epithelial cells as well as that of uPAR and PAI 1 the effects involve posttranscriptional regulatory components . ^^^ Expression of uPA , uPAR , and PAI 1 by the lung epithelium , as well as the ability of uPA to induce other components of the fibrinolytic system , involves posttranscriptional regulation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) and its inhibitors type 1 ( PAI 1 ) and type 2 ( PAI 2 ) are considered to have a key role in the process of invasion and metastasis . ^^^ We investigated the differences in uPA , PAI 1 and PAI 2 concentrations in primary cutaneous melanoma and normal skin and correlations with well established melanoma prognostic factors . ^^^ The uPA concentrations were determined in 36 pairs of triton extracts , and the PAI 1 and PAI 2 concentrations in 43 pairs of cytosols prepared from the tumour and adjacent normal tissue samples ( matched pairs ) . ^^^ The uPA , PAI 1 and PAI 2 concentrations were measured by enzyme linked immunosorbent assay ( ELISA ) . ^^^ Significantly higher concentrations of both uPA and PAI 1 were measured in melanomas than in normal surrounding skin ( uPA : 1 . 08 vs 0 . 48 ng / mg total protein ( mgp ) , p < 0 . 001 ; PAI 1 : 14 . 07 vs 2 . 07 ng / mgp , p < 0 . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PA inhibitor 1 ( PAI 1 ) is the predominant inhibitor of soluble and receptor bound uPA . ^^^ These data indicate that pneumonia is associated with inhibition of the fibrinolytic system at the site of the infection secondary to increased production of PAI 1 ; an intact fibrinolytic response is not required for an adequate host response to respiratory tract infection , however , suggesting that the previously described role of uPA and uPAR are restricted to their function in cell migration . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunoassays of urokinase ( uPA ) and its type 1 inhibitor ( PAI 1 ) in detergent extracts of breast cancer tissue . ^^^ Two immunoassays for quantitation of the biological markers uPA and PAI 1 were evaluated for their use with detergent extracts of breast cancer tissue . ^^^ The assay detected free uPA as well as uPA in complex with PAI 1 and / or with its receptor . ^^^ The assay detected both free PAI 1 and uPA : PAI 1 complex . ^^^ Highly significant associations between tumour tissue uPA and PAI 1 levels and prognosis were verified in a cohort of 164 lymph node negative primary breast cancer patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunohistochemical studies revealed that although dermal fibroblasts of normal scars and keloids expressed both urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) , keloid fibroblasts had a much higher PAI 1 expression . ^^^ In long term three dimensional fibrin gel cultures ( the in vitro fibroplasia model ) , normal fibroblasts expressed moderate and modulated activity levels of uPA and PAI 1 . ^^^ In contrast , keloid fibroblasts expressed a persistently high level of PAI 1 and a low level of uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These data suggest that uPAR deficiency suppresses renal Mphi recruitment , but the absence of this scavenger receptor actually accentuates the fibrogenic response , likely due in part to the delayed clearance of angiogenic / profibrotic molecules such as PAI 1 and decreased receptor associated uPA activity . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , renal expression of several genes that regulate plasmin activity were similar in both genotypes , including uPA , tPA , PAI 1 , protease nexin 1 , and alpha 2 antiplasmin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cancer tissues from 101 gastric cancer patients were assayed immunohistochemically for expression of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , PA inhibitor 1 ( PAI 1 ) and VEGF protein . ^^^ The positive rates of uPA , uPAR , PAI 1 , VEGF expression were 22 . 8 % , 32 . 7 % , 36 . 6 % and 26 . 7 % , respectively . ^^^ Positive staining was observed in tumor cells ( uPA , uPAR , VEGF ) , or in both tumor cells and stromal cells ( PAI 1 ) . ^^^ The expressions of uPA , uPAR , PAI 1 and VEGF were significantly correlated with the clinicopathological factors : uPA , depth of tumor invasion , differentiation , lymphatic and vascular invasion ; uPAR , tumor size , depth , lymph node involvement , differentiation , vascular invasion ; PAI 1 , tumor size , depth , lymph node involvement , differentiation , vascular invasion ; VEGF , differentiation , vascular invasion . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , PAI 1 and HKa did not affect fibronectin dependent adhesion or cell survival . uPA did not influence apoptosis in vitronectin or fibronectin adherent cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The processes of ovarian cancer dissemination are characterized by altered local proteolysis , cellular proliferation , cell attachment , and invasion , suggesting that the urokinase type plasminogen activator ( uPA ) and its specific inhibitor ( plasminogen activator inhibitor type 1 ( PAI 1 ) ) could be involved in the pathogenesis of peritoneal dissemination . ^^^ We showed previously that expression of uPA and PAI 1 in the human ovarian cancer cell line HRA can be down regulated by exogenous bikunin ( bik ) , a Kunitz type protease inhibitor , via suppression of transforming growth factor beta 1 ( TGF beta 1 ) up regulation and that overexpression of the bik gene can specifically suppress the in vivo growth and peritoneal dissemination of HRA cells in an animal model . ^^^ To test this hypothesis , we used complementary techniques in mesothelial cells to determine whether uPA and PAI 1 expression are altered by exposure to culture media conditioned by HRA cells . ^^^ Here we show the following : 1 ) that expression of PAI 1 , but not uPA , was markedly induced by culture media conditioned by wild type HRA cells but not by bik transfected clones ; 2 ) that by antibody neutralization the effect appeared to be mediated by HRA cell derived TGF beta 1 ; 3 ) that exogenous TGF beta 1 specifically enhanced PAI 1 up regulation at the mRNA and protein level in mesothelial cells in a time and concentration dependent manner , mainly through MAPK dependent activation mechanism ; and 4 ) that mesothelial cell derived PAI 1 may promote tumor invasion possibly by enhancing cell cell interaction . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MATERIALS AND METHODS : We prospectively evaluated VEGF and microvessels density on tumor specimen and cytosolic levels of uPA and PAI 1 . ^^^ Using the median value as cutoff for the statistical analysis , we found significant correlation between cytosolic levels of uPA and PAI 1 ( r = 0 . 61 ; p < . 0001 ) , between VEGF and steroid hormone receptor status ( p = . 01 ) , between PAI 1 and tumor grading ( p = . 009 ) , and between uPA and tumor size greater than 1 cm ( p = . 04 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This effect was accompanied by a strong reduction in TGFbeta responsivess of the slow responder genes pthrp , pai 1 and upa , while the reactivity of the fast responder gene smad 7 to TGFbeta remained almost unchanged . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MAIN OUTCOME MEASURE ( S ) : Concentrations of total and active transforming growth factor beta 1 ( TGF beta 1 ) , tumor necrosis factor alpha ( TNF alpha ) , tissue type plasminogen activator ( t PA ) , urokinase plasminogen activator ( uPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) were obtained . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
VEGF and bFGF stimulation also significantly induced uPA expression , most strikingly the level of 33 kDa uPA , and increased the expression of PA inhibitor ( PAI ) 1 . ^^^ Genistein , apigenin , and 3 hydroxyflavone effectively blocked the generation of 33 kDa uPA , and further decreased the activity of the 55 kDa uPA and the expression of PAI 1 below the basal level . ^^^ In conclusion , these data suggest that genistein , apigenin , and 3 hydroxyflavone inhibit in vitro angiogenesis , in part via preventing VEGF / bFGF induced MMP 1 and uPA expression and the activation of pro MMP 2 , and via modulating their inhibitors , TIMP 1 and 2 , and PAI 1 . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , a member of the serine protease inhibitor ( serpin ) superfamily , is the principal inhibitor of tPA and uPA in the fibrinolytic system . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) , a member of the serine protease inhibitor ( serpin ) superfamily , is the principal inhibitor of tPA and uPA in the fibrinolytic system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : To detect the expression of urokinase type plasminogen activator ( uPA ) and its inhibitors ( plasminogen activator inhibitors , PAI ) type 1 and type 2 in squamous cell carcinoma of human larynx and reveal the correlation of the major clinicopathologicl parameters and prognosis . ^^^ METHODS : uPA , PAI 1 and PAI 2 were detected from 104 cases squamous cell carcinoma of human larynx undergoing primary resection using immunohistochemistry ( labeled streptoavidin biotin peroxidase , SAB ) method . ^^^ Overall survival were analyzed according to Kaplan Meier and log rank statistics , the prognostic relevance of uPA , PAI 1 and PAI 2 and conventional prognostic factors were analyzed by Cox analyses . ^^^ RESULTS : uPA , PAI 1 and PAI 2 positivity were present both in neoplastic cells and in fibroblast cells and macrophages . ^^^ The total positive rate of uPA , PAI 1 and PAI 2 was 66 . 3 % , 70 . 2 % and 50 . 0 % respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of urokinase ( uPA ) and tissue type ( tPA ) plasminogen activators and their type 1 inhibitor ( PAI 1 ) were determined by immunoassay in tumor cytosols and samples of histologically unaltered adjacent mucosa in gastric cancer patients . ^^^ Gastric tumor revealed enhanced uPA and PAI 1 matched by decreased tPA in intact mucosa . ^^^ The expression of uPA and PAI 1 was particularly was high at the later stages of the disease . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A random sample of 70 of the 112 cases had plasma levels of urokinase like plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , macrophage inhibiting factor ( MIF ) , tumour growth factor beta 1 ( TGF beta 1 ) , homocysteine , and serum levels of IgA antibodies against Chlamydia pneumoniae ( IgA CP ) and Cotinine ( a nicotine metabolite ) measured . ^^^ RESULTS : the annual expansion rate correlated positively with tPA , IgA CP and S Cotinine ; r =0 . 37 ( p=0 . 002 ) , 0 . 29 ( p=0 . 006 ) and 0 . 24 ( p=0 . 038 ) , while PAI 1 , uPA , TGF beta 1 , homocysteine , and MIF did not . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The tumor cell associated urokinase type plasminogen activator system , consisting of the serine protease uPA , its substrate plasminogen , its membrane bound receptor uPAR , as well as its inhibitors PAI 1 and PAI 2 , plays an important role in these pericellular processes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Clinically relevant molecules whose expression or structure is altered include the plasminogen activator ( uPA ) and its inhibitor PAI 1 ( plasminogen activator inhibitor type 1 ) , the cell cycle regulator cyclin E , epidermal growth factor ( EGF ) , the apoptosis inhibitor bcl 2 , the cell adhesion molecule E cadherin , and the multifunctional protein beta catenin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
It consists of the serine protease uPA , its membrane bound receptor ( uPAR , CD 87 ) and one of the natural inhibitors PAI 1 or PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Results from two groups reveal a role for PAI 1 in promoting cycles of attachment and detachment of the cell from the extracellular matrix that is independent of its role as an enzymatic inhibitor of urokinase type plasminogen activator ( uPA ) . ^^^ Through the formation of a complex of integrins , uPA and its receptor , and the clearance receptors of the low density lipoprotein family , PAI 1 may promote endocytosis and recycling of these adhesion controlling proteins , allowing cycling of cellular attachment and detachment . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Vascular endothelial cells ( EC ) synthesize activators and inhibitors for fibrinolysis , tissue and urokinase plasminogen activators ( tPA and uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Prognostic and predictive value of the urokinase type plasminogen activator ( uPA ) and its inhibitors PAI 1 and PAI 2 in operable breast cancer . ^^^ Already in univariate analysis PAI 1 was the only proteolytic factor with a significant impact on DFS , which was retained in multivariate analysis ( p = 0 . 020 ) ; PAI 2 showed borderline significance in univariate analysis ( p = 0 . 0503 ) and uPA did not present as a significant prognostic factor for DFS in our patient series . ^^^ In a separate univariate analysis of DFS on patient subgroups defined by adjuvant systemic therapy , a higher risk of relapse associated with higher uPA and PAI 1 levels was found in the subgroup of patients who did not receive any treatment ; this difference did not reach the level of significance , probably due to the small number ( n = 52 ) of patients in this group ( HR 1 . 37 ; p = 0 . 71 and HR 2 . 14 ; p = 0 . 321 , respectively ) . ^^^ In contrast , the bad prognostic impact of high uPA and PAI 1 levels was lost in the subgroup of patients treated with adjuvant hormone therapy ( HR 0 . 79 ; p = 0 . 693 and HR 0 . 26 ; p = 0 . 204 , respectively ) . ^^^ The same observations were made for the uPA / PAI 1 combination . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
High levels of uPA and plasminogen activator inhibitor 1 ( PAI 1 ) correlate with poor prognosis in several cancers . ^^^ In addition to the uPA : PAI 1 ratio , the presence of PAI 2 may be an important factor in the determination of metastatic sites for prostate cancer cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Single site mutants within the Asp 355 Arg356 Pro 357 segment of PAI 1 yield guanidine activatable inhibitors ( a ) that can still form SDS stable complexes with tPA and urokinase plasminogen activator ( uPA ) , and ( b ) that have inhibition rate constants towards plasminogen activators which resemble those of the fibrosarcoma inhibitor . ^^^ Glu 351 is a specificity determinant of PAI 1 toward uPA , plasmin and thrombin , but not for tPA . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : To evaluate the role of plasminogen activator inhibitor 1 ( PAI 1 ) , urokinase plasminogen activator ( uPA ) , and tissue type plasminogen activator ( tPA ) in adhesion formation after laparoscopic surgery . ^^^ ANIMAL ( S ) : Seventy female wild type and transgenic knockout mice for PAI 1 ( PAI 1 ( / ) ) , uPA ( uPA ( / ) ) or tPA ( tPA ( / ) ) . ^^^ RESULT ( S ) : In PAI 1 , uPA , and tPA wild type mice , pneumoperitoneum enhanced adhesions . ^^^ Compared with wild type mice , basal adhesions were fewer in PAI 1 ( / ) mice and more in uPA ( / ) and tPA ( / ) mice . ^^^ The absence of pneumoperitoneum enhanced adhesions in PAI 1 ( / ) , uPA ( / ) , and tPA ( / ) mice and the increase in PAI 1 expression indicate that PAI 1 up regulation by carbon dioxide pneumoperitoneum is a mechanism of pneumoperitoneum enhanced adhesion formation . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 is like the corresponding plasminogen activator uPA ( urokinase type plasminogen activator ) consistently expressed in human breast cancer . ^^^ Paradoxically , high levels of PAI 1 as well as uPA are equally associated with poor prognosis in cancer patients . ^^^ In these tumors , the expression pattern of uPA and PAI 1 resembles that of human ductal breast cancer and plasminogen is required for efficient metastasis . ^^^ These results agree with the virtual lack of spontaneous phenotype in PAI 1 deficient mice and humans and may reflect that the plasminogen activation reaction is not rate limiting for tumor vascularization and metastasis , or that there is a functional redundancy between PAI 1 and other inhibitors of the uPA / plasmin system , masking the effect of PAI 1 deficiency . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Of the `` new ' ' tumor biologic parameters , only the measurement of the urokinase type plasminogen activator ( uPA ) and its inhibitor ( PAI 1 ) in the primary tumor of node negative patients has been adequately validated and can therefore be recommended for clinical application . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is the principal inhibitor of urokinase type plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) , and as such is thought to play an important role in the regulation of extracellular matrix remodeling . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the principal inhibitor of urokinase type plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) , and as such is thought to play an important role in the regulation of extracellular matrix remodeling . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of plasminogen activator inhibitor ( PAI ) 1 activity , uPA antigen and factor ( F ) XIIa did not significantly differ between the patient groups and healthy controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The results indicate that the biological characteristics of ATF PAI2CD were very similar to those of the wide type PAI 2 ( or mutants PAI 2 , PAI 2CD ) and to pro uPA in binding to uPAR bearing cells . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Type 1 plasminogen activator inhibitor ( PAI 1 ) is the primary inhibitor of tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , paraffin embedded material from 84 human pituitary adenomas ( acromegaly n=18 , Cushing ' s disease n=21 , prolactinoma n=18 , thyroid stimulating hormone secreting adenoma n=1 , nonsecreting adenoma n=26 ) and 9 nontumourous anterior pituitary lobes ( obtained from patients with prostate cancer ) was immunohistochemically analysed for expression of MMP 2 , MMP 9 , tissue inhibitor of metalloproteinases 2 ( TIMP 2 ) , urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and interleukin 6 ( IL 6 ) . ^^^ In pituitary adenomas , reactions were positive ( diffuse expression ) to MMP 2 ( 74 % of cases ) , MMP 9 ( 49 % ) , TIMP 2 ( 88 % ) , uPA ( 89 % ) , uPAR ( 90 % ) , tPA ( 69 % ) , and PAI 1 ( 87 % ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To date , the factors capable of regulating the coordinate expression of the urokinase type plasminogen activator ( uPA ) and its endogenous inhibitor , plasminogen activator inhibitor ( PAI 1 ) , at the maternal fetal interface remain poorly characterized . ^^^ In these studies we examined the ability of the classical form of gonadotropin releasing hormone ( GnRH ) 1 and the second , mammalian form of this hormone , GnRH 2 , to regulate uPA and PAI 1 mRNA and protein expression levels in cultures of stromal cells isolated from first trimester decidual tissues using quantitative competitive PCR and ELISA , respectively . ^^^ Cetrorelix , a GnRH receptor antagonist , inhibited the regulatory effects of GnRH 1 , but not GnRH 2 , on uPA and PAI 1 expression levels in these decidual stromal cell cultures . ^^^ Taken together , these observations suggest that GnRH 1 and GnRH 2 differentially regulate the balance between uPA and PAI 1 expression levels in the human decidua , possibly via distinct receptor mediated signaling pathways . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Pooled analysis of prognostic impact of uPA and PAI 1 in breast cancer patients . ^^^ In this report we present an extension of the pooled analysis of the prognostic impact of urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 in breast cancer patients . ^^^ We checked the consistency of the estimates for uPA and PAI 1 for relapse free survival ( RFS ) and MFS exploring possible sources of heterogeneity . ^^^ Nodal status , the most important prognostic factor for breast cancer , introduced heterogeneity in the uPA / PAI 1 survival analyses , reflecting the interaction between nodal status and uPA / PAI 1 . ^^^ The estimates for uPA and PAI 1 were found to be consistent , even when a different transformation of their values was used . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : Urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor ( PAI 1 ) , and uPA receptor ( uPAR ) are prognostic factors in various cancer types , especially breast cancer . ^^^ We sought to determine ( 1 ) whether uPA , PAI 1 , and uPAR were detectable in breast nipple aspirate fluid ( NAF ) , a physiologic fluid produced by the breast and collected noninvasively , and ( 2 ) the association of these markers in NAF with the presence of breast cancer . ^^^ PATIENTS AND METHODS : One hundred twenty NAF specimens were collected from women with and women without breast cancer . uPA , PAI 1 , and uPAR expression in NAF was measured by enzyme linked immunosorbent assay . ^^^ RESULTS : Median NAF PAI 1 , but not uPA or uPAR , expression was higher in subjects with breast cancer than in those without breast cancer , regardless of whether expression was controlled for total NAF protein level . ^^^ A multiple logistic regression model that included age , race , menopausal status , uPA , PAI 1 , and uPAR level to differentiate patients with regard to cancer risk revealed that uPA , PAI 1 , and age were each associated with risk ( P < or = 0 . 019 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The serine protease urokinase type plasminogen activator ( uPA ) , its inhibitor PAI 1 , and its cellular receptor uPA R ( CD 87 ) are of crucial importance during cellular invasion and migration , required for a variety of physio and pathophysiological processes . ^^^ Moreover , there is a growing body of evidence that cellular uPA , uPA R , and PAI 1 expression is under control of specific ECM / integrin interactions and also that integrins are regulated by components of the uPA / uPA R system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This activity was completely inhibited by plasminogen activator inhibitor 1 and by amiloride , identifying the activity as urokinase plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Substantial evidence exists which implicates the urokinase plasminogen activator system [ urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) ] in the neo vascularization , invasion and metastasis of many solid tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The levels of uPA , PAI 2 and the uPA : PAI 1 complex increased with progressive loss of histological differentiation ( p ( trend ) < 0 . 001 , < 0 . 05 and < 0 . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : Tumor expression of urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and uPA receptor ( uPAR ) are breast cancer prognostic factors . ^^^ We determined the association of uPA , PAI 1 , and uPAR levels in NAF with breast cancer ( 1 ) detection and ( 2 ) advanced disease . ^^^ METHODS : A total of 88 NAF specimens were collected from women with or without breast cancer , and uPA , PAI 1 , and uPAR expression were measured by enzyme linked immunosorbent assay . ^^^ CONCLUSIONS : NAF evaluation of uPA , uPAR , and , perhaps , PAI 1 ( significant only in univariate analysis ) may provide useful breast cancer diagnostic and prognostic information . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This study utilized mesangial cells isolated from mice with gene deletions for tPA , uPA , and plasminogen activator inhibitor 1 ( PAI 1 ) to further delineate the role of the PA / plasminogen / plasmin system in ECM accumulation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Limited prognostic value of c erbB 2 compared to uPA and PAI 1 in primary breast carcinoma . ^^^ In a retrospective study of 488 women with primary breast cancer , after a median follow up of 10 years , we sought interactions between disease free survival ( DFS ) and overall survival ( OS ) and tumor antigen levels of two components of the plasminogen system , urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 , and the transmembrane growth factor receptor c erbB 2 . ^^^ We used ELISAs ( American Diagnostica , Greenwich , CT , USA ) to quantify uPA and PAI 1 antigen levels in cytosols , and a double monoclonal antibody based assay ( EIA ) ( Ciba Corning Diagnostics , Alameda , CA , USA ) to quantify c erbB 2 in membrane extracts of the same tissues . ^^^ Weak positive correlations were found between uPA and c erbB 2 ( r ( s ) = 0 . 146 ; p = 0 . 001 ) and between PAI 1 and c erbB 2 ( r ( s ) = 0 . 154 ; p < 0 . 001 ) . ^^^ In the overall population , using univariate analyses , c erbB 2 overexpression and high uPA and PAI 1 antigen levels ( > 300 IU / mg , > 1 . 40 ng / mg and > 5 . 53 ng / mg , respectively ) were significantly associated with shorter DFS ( p = 0 . 003 , p < 0 . 001 and p < 0 . 001 , respectively ) and OS ( p < 0 . 001 in all cases ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Interestingly , urokinase plasminogen activator ( uPA ) and and PA inhibitor 1 ( PAI 1 ) levels were not significantly affected by HA of increasing MW ; however , the PAI 1 to uPA ratio showed a slight , yet nonsignificant increase . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Twenty PVR , PDR or pucker membranes were examined to identify the cells with cell specific markers and to detect the expression of urokinase ( uPA ) , tissue type plasminogen activator ( tPA ) or plasminogen activator inhibitor 1 ( PAI 1 ) by in situ hybridization and by immunohistochemistry . ^^^ RESULTS : In PVR , uPA , tPA and PAI 1 were expressed by retinal pigment epithelial ( RPE ) cells , macrophages or retinal glial cells . ^^^ Semiquantitative analysis in in situ hybridization and immunohistochemistry results demonstrated no notable differences in uPA , tPA or PAI 1 expression between PDR and PVR membranes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator ( urinary plasminogen activator , urokinase ) ( uPA ) and its PA 1 type 1 inhibitor are not only prognostically but also predictively significant and support clinical decisions on therapy in primary carcinoma of the breast ] . uPA and PAI 1 are the first novel tumor biological prognostic factors in breast cancer for which the prognostic impact has been validated at the highest level of evidence and hence all evaluation criteria for transfer into clinical practice have been fullfilled . ^^^ Breast cancer patients with high uPA and / or PAI 1 levels in their primary tumor tissue have a significantly lower chance for cure than patients with low levels of both uPA and PAI 1 . ^^^ Our research that was honored with the Schmidt Matthiesen Award 2002 shows for the first time that uPA and PAI 1 are not only prognostic factors but also have a predictive impact with regard to response to adjuvant chemotherapy . ^^^ Patients with high uPA / PAI 1 derive a significantly greater benefit from adjuvant chemotherapy than patients with low uPA / PAI 1 . ^^^ Benefit from adjuvant endocrine therapy is independent of uPA / PAI 1 status . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The binding of plasminogen activator inhibitor 1 ( PAI 1 ) to serine proteinases , such as tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) , is mediated by the exosite interactions between the surface exposed variable region 1 , or 37 loop , of the proteinase and the distal reactive center loop ( RCL ) of PAI 1 . ^^^ We have used protein engineering , stopped flow fluorimetry , and rapid acid quenching techniques to elucidate the role of exosite interactions in the neutralization of tPA , uPA , and beta trypsin by PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The degradation of basement membranes by tumor cells involves secretion and activation of proteinases , such as matrix metalloproteinases ( MMPs ) and the plasminogen activation system ( uPA , tPA , PAI 1 ) , and results from an imbalance between their inhibitors and activators , controlled by various growth factors or cytokines . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Several new factors that may better describe tumour behaviour , like proliferation rate ( determined by thymidine labelling index , S phase fraction , mitotic index , or Ki 67 ) , presence of disseminated tumour cells , as well as expression of invasion factors ( urokinase type plasminogen activator uPA and its inhibitor PAI 1 ) and of cell cycle genes ( cyclin E ) , as well as gene expression patterns ( ' genomic profiling ' ) are currently discussed as future methods of risk assessment and also as tools for prediction of response to specific therapy modalities . ^^^ Among the aforementioned factors , only the invasion factors uPA and PAI 1 have reached the highest levels of evidence and are mature enough to be transferred into clinical routine : their prognostic impact has been shown in several retrospective and prospective studies and in a pooled analysis of almost 3 , 500 node negative patients . ^^^ Thus , in order to correctly assess the individual risk and to design an adequate adjuvant treatment plan for node negative breast cancer patients , we recommend to use uPA and PAI 1 as additional criteria together with grading and age . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
AIM : To evaluate the relationship between uPA , PAI 1 , CEA , PI3K and metastatic potential in three colorectal tumor cell lines . ^^^ Urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) were determined using ELISA in colorectal carcinoma WiDr , HT 29 and HT 29d cell lines with different metastatic potentials . ^^^ The level of uPA and PAI 1 is positively correlated with the metastatic capacity of tumor cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : We detected MMP 7 , urokinase plasminogen activator ( uPA ) and PAI 1 in both Matrigels , TIMP 2 was detected only in regular Matrigel and no MMP 1 or TIMP 1 was detected in either matrix . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Molecular research into the invasiveness of HCC identified some factors positively related to invasiveness , P 16 and P 53 mutation , H ras , c cerbB 2 , mdm 2 , transforming growth factor ( TGF ) , epidermal growth factor receptor ( EGF R ) , matrix metalloproteinase 2 ( MMP 2 ) , urokinasetype plasminogen activator ( uPA ) , its receptor ( uPA R ) and inhibitor ( PAI 1 ) , intercellular adhesion molecule 1 ( ICAM 1 ) , vascular endothelial growth factor ( VEGF ) , platelet derived endothelial cell growth factor ( PD ECGF ) , and basic fibroblast growth factor ( bFGF ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the last few months , there have been three sets of new , provocative data that might have important implications for the daily prescription of adjuvant chemotherapy ( CT ) in the future . ( 1 ) Urokinase type plasminogen activator ( UPA ) and type 1 plasminogen activator inhibitor ( PAI 1 ) , two molecular markers of invasion already known for their powerful prognostic value in node negative breast cancer , seem to predict for enhanced benefit from adjuvant CT , while the benefit from adjuvant endocrine therapy seems independent of them . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Renal gene expressions of type 1 plasminogen activator inhibitor ( PAI 1 ) , tissue type PA ( tPA ) , and urokinase type PA ( uPA ) were examined by real time PCR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Since PCI itself did not affect the proliferation rate of Caki 1 cells or cell expression of uPA in vitro , the effect of uPA , PCI , heat inactivated PCI and plasminogen activator inhibitor ( PAI ) 1 on the invasive potential of cultured RCC cells was evaluated . ^^^ The in vitro invasiveness of Caki 1 cells , which express uPA , was significantly enhanced by the addition of uPA , and it was inhibited by anti uPA antibody , PCI and PAI 1 , but not by heat inactivated PCI . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This system comprises of , among others , the urokinase type plasminogen activator ( uPA ) and its main inhibitor ( PAI 1 ) . ^^^ In this study we investigated whether the uPA : PAI 1 complex is associated with the responsiveness of patients with primary breast cancer to adjuvant systemic therapy . ^^^ Quantitative enzyme linked immunosorbent assays were used to assess the levels of uPA , PAI 1 , and uPA : PAI 1 complex in 1119 tumors of patients with primary invasive breast cancer . ^^^ High uPA : PAI 1 complex levels were correlated with an adverse histological grade , and inversely associated with negative estrogen and progesterone receptor status . ^^^ High tumor levels of uPA : PAI 1 complex predicted an early relapse in the univariate relapse free survival analysis ( P < 0 . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase plasminogen activator ( uPA ) system consists of the serine protease uPA , its glycolipid anchored receptor , uPAR and its 2 serpin inhibitors , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) . ^^^ The prognostic value of uPA / PAI 1 in axillary node negative breast cancer patients was recently validated using both a prospective randomised trial and a pooled analysis , i . e . , in 2 different Level 1 Evidence studies . ^^^ Assay of uPA and PAI 1 may thus help identify low risk node negative patients for whom adjuvant chemotherapy is unnecessary . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHOD : We studied urokinase ( uPA ) , tissue type plasminogen activator ( tPA ) , urokinase receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) expression by in situ hybridization and by immunohistochemistry in 14 NF 2 and 15 sporadic patients with 34 schwannomas . uPAR and vitronectin immunohistochemistry were also studied . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Vascular endothelial growth factor ( VEGF ) and such plasminogen activation system components as uPA , PAI 1 and tPA were determined by enzyme immunoassay methods in endometrial tumors from 121 patients and 18 samples of endometrial hyperplasia of varying degree . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVES : To measure the plasma levels of urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) , and study the relationship between the plasma levels of uPA , PAI 1 and the serum albumin ( Alb ) , collagen type 4 ( CIV ) , the serum hyaluronic acid ( HA ) , prothrombin time ( PT ) and prothrombin activity ( PTA ) in patients with different stages of liver cirrhosis following chronic hepatitis B . ^^^ The plasma levels of uPA , uPAR , PAI 1 and the serum levels of HA , CIV were detected by ELISA . ^^^ RESULTS : With the progression of hepatic fibrosis , the plasma levels of uPA , uPAR and PAI 1 were ( 1 . 36+ / 0 . 43 ) microg / L , ( 3 . 03+ / 1 . 48 ) microg / L and ( 24 . 09+ / 7 . 14 ) microg / L respectively in group A , ( 1 . 79+ / 0 . 62 ) microg / L , ( 4 . 80+ / 2 . 22 ) microg / L and ( 41 . 40+ / 17 . 52 ) microg / L respectively in group B . ^^^ There was negative correlation between the plasma levels of uPA and the serum PCIII ( r= 0 . 4785 , P < 0 . 05 ) in child A , but , positive correlation between the plasma PAI 1 and the serum HA ( r=0 . 5447 , P < 0 . 01 ) in child C . ^^^ The value of PAI 1 / uPA was significantly decreased in child A , but increased in child B and child C . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In situ localization of mRNA for the fibrinolytic factors uPA , PAI 1 and uPAR in endometriotic and endometrial tissue . ^^^ We have previously demonstrated elevated levels of the fibrinolytic factors urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor ( PAI 1 ) in endometriotic tissue and endometrium from women with endometriosis . ^^^ The aim of the present study was to localize the uPA , PAI 1 and urokinase plasminogen activator receptor ( uPAR ) mRNA in endometriotic tissue and in endometrium both from women with and without endometriosis . ^^^ With in situ hybridization , we found that uPA mRNA seems to be up regulated in endometriotic glands and endometrial stroma as well as PAI 1 mRNA in endometriotic and endometrial stroma from women with endometriosis . uPAR mRNA likewise appears to be up regulated in both glands and stroma in endometriotic tissue and in endometrial glands from patients compared to endometrial glands and stroma from healthy women . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
XR 5967 , a diketopiperazine , dose dependently inhibited the activity of human and murine PAI 1 , towards urokinase plasminogen activator ( uPA ) , with IC 50 values of 800 nM and 8 . 3 microM , respectively . ^^^ This was confirmed by SDS PAGE , revealing that XR 5967 inhibited complex formation between PAI 1 and uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To clarify the role of proteins involved in the regulation of fibrinolysis during corneal angiogenesis , we have studied corneal vessel formation in mice deficient for urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , plasminogen , plasminogen activator inhibitor 1 ( PAI 1 ) and thrombin activatable fibrinolysis inhibitor ( TAFI ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , there was no significant difference of plasminogen activator inhibitor 1 ( PAI 1 ) , pro uPA , and tissue type plasminogen activator ( tPA ) concentrations in the medium between dDAVP treatment and control . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TGF beta 1 also downregulated urokinase type plasminogen activator ( uPA ) activity while upregulating PA inhibitor ( PAI ) 1 and thrombospondin ( TSP ) 1 gene expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Differential localization and expression of urokinase plasminogen activator ( uPA ) , its receptor ( uPAR ) , and its inhibitor ( PAI 1 ) mRNA and protein in endometrial tissue during the menstrual cycle . ^^^ Cyclic variation and distribution of uPA , uPAR and plasminogen activator inhibitor 1 ( PAI 1 ) mRNA were examined by in situ hybridization , real time PCR and northern blot in normal endometrium . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activation system includes the urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) , among other molecules . ^^^ Both uPA and PAI 1 are established prognostic factors for patients with breast carcinoma . ^^^ In the current study , the authors investigated whether the complex of uPA with PAI 1 is also associated with the natural course of this malignancy . ^^^ METHODS : Cytosolic levels of uPA , PAI 1 , and the uPA : PAI 1 complex were measured in tumor tissue from 576 patients with lymph node negative invasive breast carcinoma using quantitative enzyme linked immunosorbent assays . ^^^ RESULTS : uPA : PAI 1 complex levels were positively associated with adverse histologic grade and inversely correlated with estrogen and progesterone receptor status . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , enzyme linked immunosorbent assays ( ELISA ) of uPA antigen , and the activities of tissue plasminogen activator ( tPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) were not statistically different from those in control experiments . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
LRP protein was reduced and extracellular accumulation of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) proteins were greater in uPAR / cultures . ^^^ These data suggest that uPAR deficient kidney fibroblasts express lower levels of its scavenger co receptor LRP , resulting in greater extracellular accumulation of uPA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasma levels of fibrinopeptide A ( FPA ) , fibrin d dimer , thrombin antithrombin ( TAT ) complex , prothrombin fragment 1 . 2 ( F1 . 2 ) , urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( t PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) were measured before and after therapy , as was the cellular expression of the genes for tissue factor ( TF ) and interleukin 1 beta ( IL 1 beta ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is the major physiological inhibitor of both tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) . ^^^ In this study , we identify WAY 140312 as a structurally novel small molecule inactivator of PAI 1 , compare its inhibitory activity with other previously identified small molecule inhibitors , and investigate the mechanism of inactivation of PAI 1 in the presence of both tPA and uPA . ^^^ Immunoblot analysis demonstrated that WAY 140312 near the IC ( 50 ) inhibited the complex formation between either tPA or uPA and PAI 1 . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the major physiological inhibitor of both tissue type plasminogen activator ( tPA ) and urokinase type plasminogen activator ( uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen system participates in this process with the balance between urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) being a critical determinant of the extent of collagen accumulation that follows lung injury . ^^^ Because the plasminogen system is known to influence the rate of migration of epithelial cells , including keratinocytes and bronchial epithelial cells , we hypothesized that the balance of uPA and PAI 1 would affect the efficiency of alveolar epithelial cell ( AEC ) wound repair . ^^^ Using an in vitro model of AEC wounding , we show that the efficiency of repair is adversely affected by a deficiency in uPA or by the exogenous administration of PAI 1 . ^^^ The significant effect of uPA and PAI 1 on epithelial repair suggests a mechanism by which the plasminogen system may modulate pulmonary fibrosis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the study reported here we examined the expression of plasminogen activator inhibitor 1 ( PAI 1 ) , urokinase type plasminogen activator ( uPA ) , and uPA receptor ( uPAR ) , as well as the relevance of such expression to the production of type 4 collagen , a major component of extracellular matrix , in the renal tissue of rats with streptozotocin induced diabetes . ^^^ Because angiotensin 2 is involved in the synthesis of PAI 1 and uPA , we also examined the effect of benazepril , an angiotensin converting enzyme inhibitor , on the expression of PAI 1 , uPA , and uPAR messenger RNAs ( mRNAs ) and type 4 collagen protein . ^^^ We examined the expression of PAI 1 , uPA , and uPAR mRNAs through the use of in situ hybridization and that of type 4 collagen by means of immunohistochemical methods . ^^^ In control rats , we detected weak signals for PAI 1 , uPA , and uPAR mRNAs in glomeruli . ^^^ Diabetic rats exhibited high levels of expression of PAI 1 , uPA , and uPAR mRNAs and type 4 collagen protein , mainly in mesangial cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The aim of this study was to evaluate the expression of urokinase plasminogen activator ( uPA ) , its receptor ( uPAR ) and the plasminogen activator inhibitor type 1 ( PAI 1 ) in human aorta , and to balance them with the stage of atherosclerotic lesion . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The release of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI ) by GEC or whole glomeruli was assessed by ELISA , fibrin zymography and Northern blot . ^^^ The binding of AgIgG to GEC elicited a dose and time dependent increase in the release of uPA activity , as in the uPA protein and mRNA expression without modification in the release of PAI . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The net balance between urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) has been implicated in tumor cell invasion and metastasis . ^^^ These data also reflect the complex biological effect of uPA PAI 1 system . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Because absence of urokinase plasminogen activator ( uPA ) prevents development of cardiac fibrosis after experimental myocardial infarction in mice , we hypothesized that elevated activity of uPA or deficiency of the uPA inhibitor plasminogen activator inhibitor 1 ( PAI 1 ) might cause cardiac fibrosis . ^^^ We used mice with scavenger receptor ( SR ) directed , macrophage targeted uPA overexpression ( SR uPA+ / 0 mice ) and PAI 1 null mice to test these hypotheses . ^^^ We conclude : ( 1 ) either elevated macrophage uPA expression or PAI 1 deficiency is sufficient to cause cardiac macrophage accumulation and fibrosis ; ( 2 ) macrophages are important contributors to the development of cardiac fibrosis ; and ( 3 ) the heart is particularly sensitive to the effects of excess uPA activity . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumor levels of BCAR 1 were correlated with relapse free survival ( RFS ) and overall survival ( OS ) and compared with collected data on urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^ BCAR 1 levels exhibited a positive correlation with steroid hormone receptor levels , age and menopausal status , and uPA and PAI 1 levels . ^^^ When added together with uPA and PAI 1 in the multivariate model , BCAR 1 contributed independently of PAI 1 and was favored over uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : MMP 2 , MMP 9 , uPA , PAI 1 , IGF 2 , BFGF , VEGF , ANG 1 , IRS 1 , and TSP 1 were significantly ( p < or =0 . 05 ) upregulated in CIS and INV , whereas TIMP 1 , ANG 2 , MASPIN , IGF 1 R and HBEGF were unchanged . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition to inhibiting serine proteases ( mainly tPA and uPA ) , PAI 1 interacts with vitronectin ( Vn ) , fibrin or alpha ( 1 ) acid glycoprotein , interactions which are important for PAI 1 mediated effects in inflammation , tumor invasion and metastasis . ^^^ We suggest that PAI 1 , via interaction with both Act 4 and uPA , may function as a modulator of this mononuclear phagocyte response , not only in inflammation but also in tumor invasion and metastasis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We conclude that glycosylated bik attenuates TGF beta 1 elicited signaling cascades in cells possibly by abrogating the coupling between TbetaRI and TbetaRII and that this probably provides the mechanism for the suppression of uPA and PAI 1 expression . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In combination with other ECM proteins found in our analysis , PAI 1 and uPA , the association with DFI and OS became even more significant ( p < 0 . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Semi quantitative analysis was used to observe stained intensity and area of tissue type plasminogen activator , urokinas type plasminogen activator / plasminogen activator inhibitor ( tPA , uPA / PAI 1 ) in remnant renal tissue . ^^^ RESULT : In model control group , the urinary PA activity and protein expression of tPA , uPA were down regulated , but protein expression of PAI 1 , TGF beta mRNA was up regulated in remnant renal tissue . ^^^ In each treated group , the urinary PA activity and protein expression of tPA / uPA were enhanced , but the protein expression of PAI 1 , TGF beta mRNA decreased simultaneously . ^^^ CONCLUSION : Shenle capsule can delay glomerulosclersis and tubulointerstitial fibrotic lesions of remnant kidney by improving the activity of urinary PA and modulating the expression of tPA , uPA / PAI 1 and TGF beta mRNA . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis , and high levels of urokinase plasminogen activator ( uPA ) and plasminogen activator ( PA ) inhibitor 1 ( PAI 1 ) in tumors predict poor disease outcome . ^^^ Laser capture microdissection ( LCM ) was combined with plasminogen casein zymography to analyze uPA , tissue PA ( tPA ) , uPA PAI 1 complexes , and tPA PAI 1 complexes in 11 tumors and adjacent non malignant epithelium from squamous cell carcinomas of the tongue , floor of mouth , larynx , and vocal cord . uPA was detectable in all tumor samples analyzed , uPA PAI 1 complexes in three samples , and tPA in nine . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Specifically , overexpression of SRF in human lung fibroblasts upregulated urokinase type plasminogen activator ( uPA ) and its substrate Plg , whereas it downregulated plasminogen activator inhibitor ( PAI ) 1 . ^^^ To determine whether uPA , Plg , and PAI 1 were abnormally expressed in LAM in vivo , we immunostained 12 LAM cases . ^^^ Microdissection based reverse transcriptase / polymerase chain reaction further confirmed upregulation of uPA and Plg and downregulation of PAI 1 message in LAM . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have studied the expression of urokinase type plasminogen activator ( uPA ) mRNA , uPA receptor ( uPAR ) mRNA and immunoreactivity , and type 1 plasminogen activator inhibitor ( PAI 1 ) mRNA and immunoreactivity in 16 prostate adenocarcinomas and 9 benign prostate hyperplasias . uPA mRNA and uPAR mRNA expression were found in 9 and 8 of the adenocarcinomas , respectively , and in 7 and 6 of the benign hyperplasias , respectively . ^^^ No immunoreactivity and / or mRNA expression of uPA , uPAR or PAI 1 was observed in cancer cells or in other epithelial cells in any of the cases . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHOD : In a consecutive series of 127 patients resected for primary squamous cell carcinoma of human larynx , the expression of uPA and plasminogen activator inhibitors ( PAI ) type 1 , type 2 was determined immunohistochemically . ^^^ Overall survival were analyzed according to Kaplan Meier and log rank statistics , the prognostic relevance of uPA , PAI 1 , PAI 2 and conventional prognostic factors were analyzed by Cox analyses . ^^^ RESULT : These revealed a high significant inverse correlation of uPA positive expression survival time ( P = 0 . 006 ) ; and patients with PAI 2 positive expression had a significantly longer survival time than those with PAI 2 negative expression ( P = 0 . 009 ) ; in different clinicopathological parameters subgroups uPA , PAI 2 added significant survival information , whereas PAI 1 positive expression did not associate with prognoses . ^^^ Patients with uPA positive / PAI 2 negative expression had the poorest prognoses . ^^^ Multivariate analysis revealed that four independent prognostic factors for overall survival time were uPA , PAI 2 , lymph node metastasis and differentiation of tumor , P = 0 . 0002 , 0 . 0001 , 0 . 0117 , 0 . 0436 respectively , relative risk and 95 % confidence interval were 1 . 99 ( 1 . 39 to 2 . 85 ) 0 . 36 ( 0 . 212 to 0 . 609 ) , 2 . 36 ( 1 . 21 to 4 . 61 ) 1 . 51 ( 1 . 01 to 2 . 25 ) respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This difference in behavior was most likely related to the presence of excessive amounts of uPA in HLMVEC cells and the known mechanism of clearing PAI 1 / uPA / uPAR complexes from the cell surface . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The main components in plasminogen activation include plasminogen , tissue plasminogen activator ( tPA ) , urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) , and plasminogen activator inhibitors 1 and 2 ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Combined determination of urokinase type plasminogen activator ( uPA ) and its inhibitor , activator inhibitor type 1 ( PAI 1 ) , supports risk adapted individualized therapy concepts , particularly in node negative breast cancer . ^^^ Patients with node negative breast cancer with low antigen levels of uPA and PAI 1 in their primary tumor tissue have a very good prognosis and therefore may be spared the burden of adjuvant chemotherapy , whereas those with elevated uPA / PAI 1 antigen levels carry an increased risk of disease recurrence . ^^^ Recent retrospective analysis of > 3000 patients indicated that patients with breast cancer with high uPA / PAI 1 values derive a significantly greater benefit from adjuvant chemotherapy than patients with low uPA / PAI 1 levels . ^^^ Similarly , in the multicenter prospective Chemo N 0 trial , administration of cyclophosphamide / methotrexate / 5 fluorouracil based chemotherapy led to a substantial reduction in risk of disease recurrence in patients with high uPA / PAI 1 . ^^^ However , benefit from adjuvant endocrine therapy appears to be independent of a patient ' s uPA / PAI 1 status . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : The expression of uPA , tPA , urokinase receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and vitronectin was investigated by immunohistochemical staining , in addition to uPA , tPA and PAI 1 expression by in situ hybridization , in samples from eight chronic venous ulcers , five decubitus ulcers , five well granulating acute wounds and five normal skin samples . ^^^ Although no qualitative differences in expression of uPA , PAI 1 or uPAR in the wound edge keratinocytes in chronic ulcers vs . normally granulating wounds were found , their expressions were more pronounced in the granulation tissue of well granulating wounds . ^^^ CONCLUSIONS : These results suggest that in poorly healing venous leg ulcers , the pattern of tPA expression is altered in keratinocytes at the leading edge of the wound , and the patterns of tPA , uPA and PAI 1 expression are altered in the granulation tissue . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of uPA , one of the fibrinolytic enzymes , its receptor ( uPAR ) and its inhibitor 1 ( PAI 1 ) were also examined . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition to its role as an inhibitor of urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) is hypothesized to regulate epithelial cell adhesion and migration . ^^^ We have previously reported that PAI 1 may be an important regulatory factor of the uPA system in cornea . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In a chromogenic substrate based urokinse ( uPA ) / PAI 1 assay and a tissue type plasminogen activator ( tPA ) mediated clot lysis assay , ZK 4044 inhibited human PAI 1 activity with IC 50 values of 644+ / 255 and 100+ / 90 nM , respectively . ^^^ In the chromogenic substrate based uPA / PAI 1 assay , ZK 4044 was approximately 2 fold less potent against a mutant PAI 1 ( 14B 1 ) , which contains four mutations at N150H , K154T , Q319L and M354I , compared with wild type PAI 1 , suggesting that the ZK 4044 binding site on the surface of PAI 1 is close to these mutant residues . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Increased levels of tPA , uPA , uPA receptor ( uPAR ) , and their inhibitor , plasminogen activator inhibitor ( PAI ) 1 , have been found in the cerebrospinal fluid ( CSF ) of patients with bacterial meningitis . ^^^ Here , we show that expression of tPA , uPA , uPAR , PAI 1 , and PAI 2 is up regulated during experimental pneumococcal meningitis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Several cell biological studies have shown that the invasiveness of different malignant tumors ( breast , renal , prostate , gastric , ovarian cancers ) depends at least in part on the urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 . uPA converts plasminogen into plasmin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
EGFR phosphorylation and beta catenin activation were inhibited by plasminogen activator inhibitor 1 and pertussis toxin , two inhibitors of the urokinase type plasminogen activator ( uPA ) / uPA receptor system . beta Catenin activation was correlated with the phosphorylation of glycogen synthase kinase 3beta through a phosphatidylinositol 3 kinase / Akt dependent mechanism . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , we tested the hypothesis that loss of the primary inhibitor of uPA , plasminogen activator inhibitor 1 ( PAI 1 ) , would improve muscle regeneration . ^^^ Repair of the extensor digitorum longus muscle was assessed after cardiotoxin injury in wild type , uPA / , and PAI 1 deficient ( PAI 1 / ) mice . ^^^ On the other hand , uPA activity was increased in injured muscle from PAI 1 / mice to a greater extent than in wild type controls . ^^^ The injured muscles of PAI 1 null mice also demonstrated increased macrophage accumulation , contrasting with impaired macrophage accumulation in uPA deficient mice . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
LysoPC also induced the mRNA expression of urokinase type plasminogen activator ( uPA ) , uPA receptor , and plasminogen activator inhibitor 1 , but the kinetics were different from that of tPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RT PCR assay for urokinase type plasminogen activator ( uPA ) , its cellular receptor ( uPAR ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) , and tumor necrosis factor ( TNF ) alpha was performed to assess the cecal tissue . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Activities ( cath B ( AT ) , cath B ( A7 . 5 ) ) and protein levels of cath B ( C ) , cath L ( C ) , uPA , PAI 1 , uPAR [ measured by three different assays uPAR ( ADI ) , uPAR ( HD 13 ) , uPAR ( IIIF 10 ) ] and TF were measured in homogenates of lung tumour tissue and corresponding non malignant lung parenchyma . ^^^ The concentrations of cath B ( C ) , cath L ( C ) , uPA , PAI 1 , uPAR and TF were determined by ELISAs . uPAR was determined using three different ELISA formats . ^^^ The median levels of cath B ( AT ) ( 5 . 1 fold ) , cath B ( A7 . 5 ) ( 2 . 5 fold ) , cath B ( C ) , ( 8 . 5 fold ) , cath L ( C ) ( 6 . 6 fold ) , uPA ( 6 . 5 fold ) , PAI 1 ( 4 . 2 fold ) , uPAR ( ADI ) ( 2 . 2 fold ) , uPAR ( HD 13 ) ( 4 . 0 fold ) and uPAR ( IIIF 10 ) ( 2 . 6 fold ) were higher in tumour tissue compared to the lung parenchyma . ^^^ PAI 1 significantly correlated with cath B ( AT ) and cath B ( A7 . 5 ) with uPAR ( ADI ) , uPAR ( HD 13 ) , uPAR ( IIIF 10 ) with uPA , and only weakly with TF , but not with cath B ( C ) and cath L ( C ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here we examined whether the plasminogen activator inhibitor 1 and 2 ( PAI 1 and PAI 2 ) mRNA , endogenous inhibitors of tPA and uPA , are induced in the DRG following sciatic nerve transection . ^^^ Co expression of PAI 1 , 2 with tPA and uPA in DRG neurons suggests that these inhibitors may act in an autocrine manner to modulate extracellular proteolytic activity after nerve injury . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Levels of plasminogen activity , uPA , tissue plasminogen activator ( tPA ) , and their inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) were measured in tears and plasma of patients with VKC . ^^^ The presence of tPA , uPA , and urokinase receptor ( uPAR ) in conjunctival tissues were evaluated by immunohistochemistry . uPA , uPAR , and PAI 1 expression and production were measured in conjunctival epithelial cell and fibroblast cultures treated with cytokines . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Tissue type plasminogen activator deficient ( tPA ( / ) ) , urokinase type plasminogen activator deficient ( uPA ( / ) ) , plasminogen activator inhibitor 1 deficient ( PAI 1 ( / ) ) , alpha 2 antiplasmin deficient ( alpha 2 AP ( / ) ) mice , and their wild type counterparts were used . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A coordinated increase in tPA and its inhibitor PAI 1 expression in the monkey and rat CL may be instrumental in initiating luteal regression in both species , and correlated well with the timing of the closure of the implantation window , whereas high uPA activity in the CL is important for the early formation of the CL and for maintaining its function which is closely correlated to the period of establishment of the implantation window . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : To investigate whether separated and cultured endometriotic and endometrial stromal and epithelial cells release urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and soluble plasminogen activator receptor ( suPAR ) antigens in vitro . ^^^ MAIN OUTCOME MEASURE ( S ) : The antigen concentrations of uPA , PAI 1 , and suPAR in culture medium were assayed by enzyme linked immunosorbent assay . ^^^ CONCLUSION ( S ) : This study has demonstrated the basic capacity of separated epithelial and stromal cells from all three types of tissue to release uPA , PAI 1 , and suPAR without any paracrine influence , as in vivo . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Thus , the generation of plasmin involves the pro enzyme plasminogen , the urokinase type plasminogen activator uPA and its pro enzyme pro uPA , the uPA inhibitor PAI 1 , the cell surface uPA receptor uPAR , and the plasmin inhibitor alpha ( 2 ) antiplasmin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Similar expression patterns were observed for urokinase plasminogen activator ( uPA ) , uPA receptor , and plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
CLINICAL RELEVANCE : Elevated urokinase like plasminogen activator ( uPA ) and decreased plasminogen activator inhibitor 1 ( PAI 1 ) levels are predictors for restenosis . ^^^ Proteases such as uPA can effect smooth muscle cells and alter the matrix ; their activity is controlled by a series of inhibitors ( eg , PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumour associated urokinase type plasminogen activator ( uPA ) and its inhibitor PAI 1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity clinical relevance and prognostic value . ^^^ The central role of the serine protease urokinase type plasminogen activator ( uPA ) and its inhibitor , the plasminogen activator inhibitor 1 ( PAI 1 ) , in tumour invasion and metastasis becomes more and more evident . ^^^ In several studies , uPA and PAI 1 proved to be of prognostic relevance as shown for different types of cancer ( e . g . breast , stomach , lung ) . ^^^ Elevated antigen levels of uPA and / or PAI 1 predict poor outcome ( relapse free survival ) for patients afflicted with cancer . ^^^ For oral squamous cell carcinomas , however , the prognostic relevance of the tumour associated proteolytic factors uPA and PAI 1 has still to be evaluated . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Evaluation of cerebrospinal fluid uPA , PAI 1 , and soluble uPAR levels in HIV infected patients . ^^^ To evaluate the potential role of the uPAR / uPA / PAI 1 system in HIV induced blood brain barrier ( BBB ) disruption , CSF uPA dependent plasminogen activation ( PdPA ) was analyzed by casein zymography , and CSF protein levels of all three molecules were measured by ELISA . ^^^ CSF uPAR , but not uPA , PAI 1 , or PdPA levels was significantly increased in neurologically compromised HIV+ patients . ^^^ Only individual patients with severe AIDS dementia complex had increased levels of uPA ( but not PAI 1 ) which fell upon initiation of antiretroviral therapy . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen / plasmin system includes the uPA , its receptor , and its inhibitor ( plasminogen activator inhibitor 1 ) . ^^^ In previous studies , we found that uPA regulates cell surface fibrinolysis by regulating its own expression as well as that of the uPA receptor and plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
One proteolytic system involved in these processes is the urokinase type plasminogen activator ( uPA ) system , which consists of uPA , uPA receptor ( uPAR ) and uPA inhibitors 1 and 2 ( PAI 1 and PAI 2 ) . ^^^ Increased levels of uPA , PAI 1 and uPAR have been reported to be associated with poor prognosis in patients with breast cancer . ^^^ Furthermore , uPA and PAI 1 may be new prognostic markers for axillary node negative patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activator ( PA ) system comprises the 2 serine proteases , urokinase PA ( uPA ) and tissue PA ( tPA ) , the 2 serpin inhibitors , PAI 1 and PAI 2 and the uPA receptor ( uPAR ; CD 87 ) . ^^^ High levels of uPA , PAI 1 , uPA PAI 1 complex and uPAR in breast cancer tissue are associated with poor prognosis , while high levels of tPA or PAI 2 correlate with good prognosis . ^^^ In this study , pre operative plasma levels of uPA , PAI 1 , uPAR , tPA , uPA PAI 1 complex , and tPA PAI 1 complex were measured in patients with benign ( n=103 ) and malignant breast disease ( n=113 ) by immunoenzymatic assays ( ELISA ) . ^^^ While plasma antigen levels of uPA , PAI 1 , uPA PAI 1 complex and uPAR were not significantly different in the 2 groups , antigen levels of tPA and tPA PAI 1 complex were significantly higher in patients with breast carcinoma compared to the control group . ^^^ In plasma from the breast cancer patients , uPA levels correlated weakly but significantly with those of tPA ( r=0 . 20 , p=0 . 035 ) and uPAR ( r=0 . 208 , p=0 . 028 ) . tPA levels correlated strongly with tPA PAI 1 complex ( r=0 . 972 , p=0 . 0001 ) while uPA PAI 1 levels were significantly associated with PAI 1 levels ( r=0 . 534 , p < 0 . 0001 ) , tPA levels ( r=0 . 348 , p=0 . 0003 ) and tPA PAI 1 levels ( r=0 . 356 , p=0 . 002 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , As2O3 increased the expression of tissue inhibitor of metalloproteinase ( TIMP ) 1 and PA inhibitor ( PAI ) 1 , and reduced the MMP 2 , 9 , and uPA promoter activity in the presence and absence of PMA . ^^^ These results suggest that As2O3 inhibits tumor cell invasion by modulating the MMPs / TIMPs and uPA / uPAR / PAI systems of extracellular matrix ( ECM ) degradation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This study attempted to verify the existence of a relationship between SOX documented by Cu / Zn superoxide dismutase ( Cu / Zn SOD ) and fibrinolysis analyzed by tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and plasmin / antiplasmin ( PAP ) complexes in dialysis patients . ^^^ PAI 1 / uPA ratio and PAI 1 / tPA ratio were significantly decreased in CAPD and HD compared to controls , being significantly lower in CAPD patients relative to HD patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
VEC null cells also present an altered fibrinolytic activity with increases in tPA , uPA , uPAR and a strong reduction in PAI 1 , which may be correlated to the high incidence of abrupt hemorrhages in VEC null tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activation system in skeletal muscle regeneration : antagonistic roles of urokinase type plasminogen activator ( uPA ) and its inhibitor ( PAI 1 ) . ^^^ Skeletal muscle regeneration induced by injury has been analyzed in urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , plasminogen ( Plg ) and plasminogen activator inhibitor 1 ( PAI 1 ) deficient mice and has demonstrated profound effects of these molecules on the fibrotic state and the inflammatory response , which contribute to muscle repair . ^^^ In particular , the opposite roles of uPA and its inhibitor PAI 1 in this process are highlighted . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The cell associated fibrinolytic system ( urokinase type plasminogen activator , uPA ; uPA receptor , uPAR ; plasminogen activator inhibitor type 1 , PAI 1 ) is pivotal in cell invasion and proliferation . ^^^ METHODS : In SF obtained from RA patients and control subjects , uPA , uPAR and PAI 1 were measured by ELISA of cell lysates and culture medium and by RT PCR of mRNAs . uPA was also studied by zymography . ^^^ RESULTS : RA SF over express uPAR and PAI 1 and are more prone than the normal counterpart to spontaneous and uPA challenged invasion and proliferation , which are counteracted by antagonists of the fibrinolytic system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) in the articular cartilage of rabbit temporomandibular joint ( TMJ ) with disc displacement ( DD ) and to probe the relationship between fibrinolytic activity and cartilage remodeling . ^^^ The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI 1 in articular cartilage using in situ hybridization techniques . ^^^ RESULTS : The expression of uPA and PAI 1 was co expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone , while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits . ^^^ The most striking was the up regulation of uPA and PAI 1 mRNA in 4 day rabbits postoperatively at the onset of cartilage degeneration . ^^^ The strongest hybridizing signals for uPA and PAI 1 were seen in 2 week rabbits postoperatively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here , we report that prostate carcinoma cells LNCaP and PC 3 autoactivate latent full length PDGF D into its active form under serum independent conditions and that this autoactivation is inhibited by PAI 1 , a urokinase plasminogen activator ( uPA ) / tissue plasminogen activator ( tPA ) inhibitor . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Importantly , the bactericidal properties of uPA are associated with the serine protease domain of the molecule but are not dependent on its plasminogen activation potential and can not be inhibited by plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Expression of total uPA was constant , but PAI 1 levels were dramatically increased in plasma and in kidney homogenates during the course of staphylococcal infection . ^^^ Active uPA levels were inversely related to PAI 1 levels and to bacterial loads in kidney homogenates . ^^^ The decreased active uPA levels in infected organs might be due to the dramatically increased PAI 1 production during S . aureus infection . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : Extracellular fibrinolysis , controlled by the cell associated fibrinolytic system ( urokinase plasminogen activator , uPA ; uPA receptor , uPAR ; plasminogen activator inhibitor type 1 , PAI 1 ) , is involved in cartilage damage generation and in rheumatoid arthritis ( RA ) synovitis . ^^^ Since steroids reduce the rate of radiological progression of RA , we planned to evaluate in healthy and RA synoviocytes the effects of the steroid deflazacort on uPA , uPAR and PAI 1 expression , and subsequent phenotypic modifications in terms of uPA / uPAR dependent invasion and proliferation . ^^^ METHODS : uPA , uPAR and PAI 1 levels were studied by ELISA , RT PCR ( uPAR ) and zymography ( uPA ) in synoviocytes from four RA patients and four healthy controls . ^^^ In RA synoviocytes , deflazacort induced higher PAI 1 and lower uPA and uPAR levels , as well as a decrease in uPA enzymatic activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition , uPA receptor ( uPAR ) and plasminogen activator inhibitors ( PAIs ) , composed of PAI 1 and 2 , are also known to affect such activities . ^^^ The expression of uPA , uPAR , PAI 1 and PAI 2 was determined by immunohistochemistry . ^^^ RESULTS : The mean immunoreactive scores ( range 0 to 6 ) of uPA , uPAR , PAI 1 and PAI 2 were 3 . 09 , 2 . 22 , 1 . 99 and 0 . 56 , respectively . ^^^ The expression of uPA , uPAR and PAI 1 but not PAI 2 correlated negatively with cause specific survival . ^^^ Of uPA family members multivariate analysis showed that PAI 1 independently influenced cause specific survival . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) protein levels were not significantly different from sham over time ; however , the ratio of uPA to PAI 1 was decreased through 8 days . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Serial blood specimens were obtained for pharmacokinetics and levels of urokinase plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
On the 14th day adhesions were evaluated and tissue plasminogen activator ( tPA ) , urokinase plasminogen activator ( uPA ) , plasminogen activator inhibitor ( PAI ) type 1 and 2 were measured in peritoneal biopsy specimens . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) regulates the proteolytic activity of urokinase type plasminogen activator ( uPA ) and there is increasing evidence for a PAI 1 role in regulating cell migration / invasion by other mechanisms like vitronectin ( VN ) binding and lipoprotein receptor related protein ( LRP ) binding . ^^^ We examined the role of PAI 1 to interact with uPA , VN , and LRP in MDA MB 435 breast cancer and SKOV 3 ovarian cancer cells in a wound induced cell migration assay . ^^^ However , manipulation of the endogenous plasminogen activator system ( using blocking antibodies to PAI 1 and to uPA ) in wound induced SKOV 3 cell migration demonstrated an important role for uPA inhibition by PAI 1 that was dependent on plasminogen . ^^^ These findings contribute to the overall complexity of the role of PAI 1 in regulating cell migration ; especially since both VN binding and uPA inhibition are involved in suppressing wound induced breast and ovarian cancer cell migration . . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) regulates the proteolytic activity of urokinase type plasminogen activator ( uPA ) and there is increasing evidence for a PAI 1 role in regulating cell migration / invasion by other mechanisms like vitronectin ( VN ) binding and lipoprotein receptor related protein ( LRP ) binding . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In eighty seven patients with CRC , the levels of IL 8 , and VEGF as representative angiogenic factors and urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and PAI 2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues . ^^^ The IL 8 level was significantly associated with tumor size , depth of infiltration , Dukes stage , and liver metastasis , and also significantly correlated with the levels of VEGF , uPAR , uPA , and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) inhibited this PAI 1 action in a dose dependent manner . ^^^ The inhibitory effect of antibody to uPA receptor ( uPAR ) on PAI 1 induced TGF beta function suggested that uPAR mediated the cellular effect of PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To clarify the role of H . pylori infection in the processes of destruction of the extracellular matrix and basement membrane in cancerous tissue , the effect of H . pylori on the expressions of uPA , uPAR and PAI 1 in cancer cells was investigated . ^^^ The specific inductions of uPA , uPAR and PAI 1 mRNA were examined by reverse transcription polymerase chain reaction ( RT PCR ) amplification . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Interestingly , we observed that fibrin also induced the expression of tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 by casein zymographic and reverse zymographic analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : The rat model of portal branch ligation ( PBL ) was compared with partial hepatectomy ( PH ) and sham operation ( SO ) and evaluated for the expression of heat shock protein 70 ( hsp 70 ) , heme oxygenase 1 ( hmox 1 ) , early growth response gene 1 ( Egr 1 ) and urokinase type plasminogen activator ( uPA ) , its inhibitor ( PAI 1 ) and receptor ( uPAR ) . ^^^ PAI 1 specific mRNA was transiently elevated at 3 48 h after PBL in the atrophying lobes , whereas uPA and uPAR were unaffected in comparison with PH or SO . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MAIN OUTCOME MEASURE ( S ) : After 24 hours ' incubation , tissue plasminogen activator ( tPA ) , urokinase plasminogen activator ( uPA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) levels were determined in medium and cell lysates by using ELISA techniques . ^^^ RESULT ( S ) : In medium of co cultures , tPA and PAI 1 concentrations were statistically significantly increased compared with the case of monocultures , whereas uPA concentration was statistically significantly decreased . ^^^ In cell lysates of co cultures , PAI 1 concentration was statistically significantly increased compared with the case of monocultures , whereas tPA and uPA were unaffected . ^^^ Treatment with sodium hyaluronate statistically significantly decreased PAI 1 and uPA concentrations in medium of monocultures but decreased uPA concentration only in medium of co cultures , compared with the case of controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Levels of sputum interleukin ( IL ) 8 , IL 10 , interferon ( IFN ) gamma , tumor necrosis factor ( TNF ) alpha , human cationic antimicrobial protein 18 ( CAP 18 ) , urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor ( PAI ) 1 were determined . ^^^ CAP 18 levels were elevated in CF and COPD patients compared to control subjects , while asthma patients had reduced CAP 18 levels . uPA levels were similar but uPAR was elevated in CF and COPD patients more so than in asthma patients , while PAI 1 levels were elevated in all three disease groups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The most upregulated gene identified encodes plasminogen activator inhibitor 1 ( PAI 1 , Serpine 1 ) , a protease inhibitor that blocks urokinase plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) activity . ^^^ Because PAI 1 , uPA , and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling , we evaluated the role of PAI 1 in cholestatic liver injury by comparing the injury and repair processes in wild type ( WT ) and PAI 1 deficient ( PAI 1 / ) mice after BDL . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : We used OVCAR 3 cells and the following methods : cell migration assay , time lapse video microscopy , real time PCR , assays for cellular binding of 125I uPA and cellular degradation of 125I uPA : PAI 1 complex , biosynthetic labeling using 35S methionin , Western blot , Northern blot , and ELISAs for uPA , PAI 1 , and uPAR . ^^^ RESULTS : EGF up regulates both protein and mRNA not only for uPAR , but also for the ligand uPA and its inhibitor PAI 1 . ^^^ In addition , EGF treatment resulted in decreased degradation of radiolabeled uPA : PAI 1 complex . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This association has been intriguing since PAI 1 is known to inhibit urokinase plasminogen activator ( uPA ) that converts plasminogen to plasmin , which is actively involved in tumor progression and invasion . ^^^ The present study suggests that PAI 1 , besides its uPA inhibiting function , has a role in cancer progression by protecting tumor cells from undergoing apoptosis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The increased levels of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) and type 1 PA inhibitor ( PAI 1 ) are reported in human renal cell carcinoma ( RCC ) . ^^^ In this study , we examined the effect of expression of Cx 32 gene on the production of uPA , uPAR and PAI 1 , and on the induction of PAI 1 stimulated by hypoxia in a human metastatic RCC cell line , Caki 1 cells . ^^^ Cx 32 expression decreased both mRNA level and production of PAI 1 , uPA and uPAR in Caki 1 cells . ^^^ PP 1 , a Src inhibitor , significantly decreased PAI 1 , uPA , uPAR and HIF alpha mRNA levels in Caki 1 cells . ^^^ These results suggest that Cx 32 might reduce PAI 1 , uPA and uPAR production in metastatic RCC cells via the inhibition of Src dependent induction of HIF 1alpha and HIF 2alpha gene expression and that Cx 32 might suppress hypoxia inducible gene expression under hypoxic conditions . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To verify the applicability of the cell invasion model , multilayer cell constructs of oral squamous cell carcinoma and oral mucosal fibroblasts were exposed to extrinsic urokinase type plasminogen activator ( uPA ) or plasminogen activator inhibitor ( PAI 1 ) , which are known effectors of cell migration . ^^^ Microscopic study showed that the presence of uPA enhanced cell invasion , while PAI 1 inhibited cell migration . ^^^ Western blot and zymographic analysis demonstrated that hypoxia up regulated uPA and matrix metalloproteinases ( MMPs ) expression and activity ; conversely , PAI 1 level was down regulated in response to hypoxic challenge as compared to normoxic condition . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This turnover is regulated by matrix metalloproteinases ( MMPs ) , tissue inhibitor of matrix metalloproteinases ( TIMPs ) , and the plasminogen activation system , including tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ In this study , we examined the effect of IL 1alpha on the expression of the MMPs , TIMPs , tPA , uPA , and PAI 1 genes in osteoblasts derived from the rat osteosarcoma cell line ROS 17 / 2 . 8 . ^^^ The levels of MMPs , TIMPs , uPA , tPA , and PAI 1 expression were estimated by determining the mRNA levels using real time RT PCR and by determining protein levels using ELISA . ^^^ These results suggest that IL 1alpha stimulate bone matrix turnover by increasing MMPs , tPA , and uPA production and decreasing PAI 1 production by osteoblasts , and incline the turnover to the resolution . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We analyzed cDNA expression by using the CNIO OncoChipTM , a cDNA microarray containing a total of 6386 genes represented by 7237 clones . uPA , uPAr , tPA , PAI 1 and PAI 2 were also studied at RNA and protein levels . ^^^ Microarrays of cDNA expression , RT PCR and Western blot performed in IMR 90 E1A expressing cells showed downregulation of uPA , uPAr , tPA , PAI 1 and upregulation of PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here , we show that 1 ) higher frequency of spontaneous 3LL lung metastasis was observed in Bik / mice compared to Bik+ / + mice , suggesting that bikunin deficiency increases the sensitivity of mice to lung metastasis ; 2 ) administration of exogenous bikunin caused a significant reduction of lung metastasis in Bik / and Bik+ / + mice ; 3 ) primary and metastatic tumors significantly upregulated uPA and PAI 1 expression in Bik / mice relative to Bik+ / + mice at least through phosphorylation of ERK1 / 2 and 4 ) exogenous bikunin suppressed phosphorylation of ERK1 / 2 and upregulation of uPA and PAI 1 expression in 3LL cells in response to G CSF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The abundance of mRNA encoding PN 1 , tissue type PA ( tPA ) , urokinase ( uPA ) and PA inhibitor 1 ( PAI 1 ) were initially upregulated by human chorionic gonadotropin ( hCG ) in bovine preovulatory follicular wall homogenates . ^^^ PN 1 , PAI 1 and tPA mRNA expression then decreased near the expected time of ovulation , whereas uPA mRNA levels remained high . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The components of the plasminogen activator ( PA ) system ( urokinase type PA , uPA ; PA inhibitors , PAI 1 / 2 ; uPA receptor , uPAR ) have been implicated in the local degradation of the extracellular matrix ( ECM ) and PCa progression . ^^^ The aim of this study was to test the possible effects of the treatment with an agonist ( Leuprolide , GnRH A ) and an antagonist ( Cetrorelix , GnRH ANT ) of GnRH on the expression and activity of uPA and PAI 1 in the conditioned media of DU 145 and PC 3 , two PCa androgen independent cell lines . ^^^ The results obtained in DU 145 and PC 3 cells show that both GnRH A and GnRH ANT : 1 ) inhibit cell proliferation ; 2 ) significantly decrease the enzymatic activity and the secretion of uPA ; 3 ) significantly increase the protein levels of PAI 1 ; 4 ) induce a significant decrease of the migratory and invasion PCa capabilities . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study we ( a ) evaluated the association between survivin and HER 2 , vascular endothelial growth factor ( VEGF ) and uPA / PAI 1 expression and ( b ) defined its effect on clinical outcome in a large breast cancer patient cohort . ^^^ Increased survivin levels were significantly associated with high nuclear grade ( P < 0 . 0001 ) , negative hormone receptor status ( P = 0 . 0028 ) , HER 2 overexpression ( P = 0 . 0094 ) , VEGF expression ( P < 0 . 0001 ) , high uPA ( P = 0 . 0002 ) and PAI 1 levels ( P = 0 . 0002 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We wanted to study plasminogen activators , urokinase ( uPA ) and tissue type ( tPA ) and their inhibitor PAI 1 , which have not earlier been studied comprehensively in cutaneous NF 1 related tumors . ^^^ We analyzed the distribution of uPA , tPA and PAI 1 antigen level by immunohistochemistry and mRNA level by in situ hybridization , to identify which cells are primarily involved in proteolytic activity and plasminogen activation . ^^^ Large extent of tumor cells of Schwann cell origin and prominent expression levels of uPA , tPA and PAI 1 indicated that these cells are responsible for the main source of PA components in cutaneous NF 1 related neurofibromas . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A multiplexed fluorescence immunoassay using a novel planar waveguide technology based microarray system , ZeptoMARK ( Zeptosens ) , was developed to detect simultaneously urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and vascular endothelial growth factor ( VEGF ) in extracts of breast cancer tissues . ^^^ The three analytes assay was cross validated with single analyte ELISA / chemiluminescence immunosorbent assay tests , revealing good correlations and enhanced assay sensitivities ( LODs ) of 1 pg / mL for uPA , 33 pg / mL for PAI 1 , and 1 pg / mL for VEGF . ^^^ The uPA , PAI 1 , and VEGF results obtained from 50 breast cancer cytosols using the protein array system demonstrated that the microarray based multiplexed assay is a sensitive and robust tool to be used for the simultaneous quantification of cancer markers in small breast cancer tissue samples ( core biopsies ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
As reported previously for PAI 1 , inhibition of uPA by PAI 2 significantly increased the affinity of the complex for LRP ( K ( D ) of 36 nm for uPA PAI 2 versus 200 nm for uPA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The activities of tissue and urokinase plasminogen activators ( tPA and uPA , respectively ) , the relative inhibition of tPA , and the amounts of plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 , respectively ) in cell free saliva were studied . ^^^ The activities of tPA and uPA , and tPA inhibition , were measured using in house microtiter plate assays , and PAI 1 and PAI 2 levels were measured using commercial enzyme linked immunosorbent assay ( ELISA ) kits . ^^^ Tissue plasminogen activator , PAI 1 , and PAI 2 were evident in salivary gland tissue , whereas the expression of uPA was low . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : We compared the antigenic values of urokinase type PA ( uPA ) , soluble uPA receptor ( suPAR ) , and PA inhibitor type 1 ( PAI 1 ) and the levels of matrix metalloproteinase 2 ( MMP 2 ) and MMP 9 in 63 synovial fluid ( SF ) samples from knee joints of 38 patients with gouty arthritis and 20 SF samples from knee joints of 20 patients with osteoarthritis ( OA ) . ^^^ RESULTS : The increases of uPA , suPAR , and PAI 1 antigenic values in SF were associated with increased levels of latent MMP 9 ( pro MMP 9 ) ( p < 0 . 001 , p < 0 . 001 , p < 0 . 001 , respectively ) in gouty arthritis , whereas a correlation was not observed between uPA , suPAR , and PAI 1 antigenic values and MMP 2 levels . ^^^ Increased uPA , suPAR , and PAI 1 antigenic values in gouty arthritis SF were also correlated to each other ( p < 0 . 001 , p < 0 . 001 , p < 0 . 001 ) . ^^^ In gouty arthritis SF , no significant relations were observed between uPA and suPAR antigenic values and leukocyte , neutrophil , or monocyte counts , while increased values of PAI 1 corresponded closely with increased leukocyte and neutrophil counts ( p = 0 . 005 , p = 0 . 004 ) . ^^^ Significantly higher values of the uPA , suPAR , and PAI 1 ( p < 0 . 001 , p < 0 . 001 , p = 0 . 012 ) appeared in SF of gouty arthritis than in SF from patients with OA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
For cellular invasive processes during a variety of physio and pathophysiological events , including cancer , a fine tuned balance between the formation and loosening of cell adhesive contacts has to occur , implicating the action of pericellular proteases ; among those , the serine protease , urokinase type plasminogen activator ( uPA ) , its inhibitor PAI 1 , and its cellular receptor uPA R ( CD 87 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In a cell free system , using tissue plasminogen activator ( tPA ) and urokinase plasminogen activator ( uPA ) to activate plasminogen , PAI 1 inhibited plasmin generation induced by both activators , whereas IGFBP 5 prevented the effects of PAI 1 on tPA but not uPA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Bone matrix turnover is regulated by matrix metalloproteinases ( MMPs ) , tissue inhibitors of matrix metalloproteinases ( TIMPs ) , and the plasminogen activation system , including tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Here , we examined the effect of mechanical stress on the expression of MMPs , TIMPs , tPA , uPA , and PAI 1 in Saos 2 cells . ^^^ The levels of MMPs , TIMPs , uPA , tPA , and PAI 1 gene expression were estimated by determining the mRNA levels using real time PCR , and the protein levels were determined using ELISA . ^^^ The expression levels of MMP 1 , MMP 2 , MMP 14 , and TIMP 1 markedly exceeded the control levels at 1 . 0g / cm ( 2 ) of compressive force , whereas the expression levels of MMP 3 , MMP 13 , TIMP 2 , TIMP 3 , TIMP 4 , tPA , uPA , and PAI 1 markedly exceeded the control levels at 3 . 0g / cm ( 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of components of the plasminogen activator system [ i . e . , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 , and uPA receptor ] was detected in six human pancreatic cancer cell lines . ^^^ Moreover , activation of PPAR gamma by ligands increased plasminogen activator inhibitor 1 and decreased uPA levels in pancreatic cancer cells , and this was accompanied by a reduction in total urokinase activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Conversely , treatment with plasminogen activator inhibitor 1 or neutralizing antibody to uPA blocked Matrigel invasion of 4T1 control cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Glucose deprivation did not increase the levels of gelatinase and plasminogen activator inhibitor 1 secretion , or the expression of cell associated uPA receptor . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We studied levels of major plasminogen activator inhibitor 1 ( PAI 1 ) , tissue type plasminogen activator ( tPA ) , and urokinase type plasminogen activator ( uPA ) in lungs of preterm infants with RDS . ^^^ METHODS : The antigen levels of PAI 1 , tPA , and uPA were measured in 262 samples of tracheal aspirate fluid collected from 37 intubated preterm infants during the first 2 postnatal weeks . ^^^ To examine the expression of PAI 1 , tPA , and uPA in lung tissue , immunohistochemical analyses were performed on autopsy specimens from 7 preterm infants with RDS and 6 newborn infants without pulmonary pathologic conditions . ^^^ RESULTS : For infants with an immature surfactant profile , as indicated by lecithin / sphingomyelin ratios in tracheal aspirate fluid of < 10 , PAI 1 levels and ratios of PAI 1 to uPA and tPA were significantly higher during postnatal days 1 to 2 , compared with infants with lecithin / sphingomyelin ratios of > or = 10 . ^^^ For preterm infants with RDS , immunohistochemical analyses demonstrated increased expression of PAI 1 , tPA , and uPA predominantly in alveolar epithelium . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Inhibition of uPA activity with natural ( plasminogen activator inhibitor 1 ) or synthetic ( amiloride ) inhibitors diminished HT hi / diss Matrigel invasion in vitro and intravasation and metastasis in vivo . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The HUVECs were treated with various concentrations of BDNF ( 25 400 ng / ml ) for different ( 6 48 hours ) , reverse transcriptase polymerase chain reaction ( RT PCR ) was used to assay MMP 2 , MMP 9 , TIMP 1 , and TIMP 2 mRNA in HUVECs , and the conditioned medium was analyzed for MMP and uPA activity by gelatin zymography and fibrin zymography , respectively . uPA , plasminogen activator inhibitor ( PAI ) 1 , tissue inhibitors of metalloproteinase ( TIMP ) 1 , and TIMP 2 were quantified by western blotting analysis . ^^^ BDNF increased uPA and PAI 1 production in a dose dependent manner . ^^^ Maximal activation of uPA and PAI 1 expression in HUVECs was induced by 100 ng / ml BDNF , while effects of 200 ng / ml and 400 ng / ml BDNF were slightly reduced in comparison with with those of 100 ng / ml . ^^^ BDNF also stimulated uPA and PAI 1 production beyond that in control cultures in a time dependent manner from 12 hours to 48 hours after BDNF treatment . ^^^ CONCLUSIONS : BDNF stimulates MMP and uPA / PAI 1 proteolytic network in HUVECs , which may be important to the acquisition of proangiogenic potential . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , a member of the serine protease inhibitor superfamily , modulates fibrinolysis by interacting with proteolytic mediators , including urokinase plasminogen activator ( uPA ) . ^^^ Although the roles of uPA and PAI 1 in plasmin generation and the degradation of fibrin are well known , recent evidence also suggests that they can participate in acute inflammatory conditions that involve neutrophil activation . ^^^ In the present experiments , we found that the addition of PAI 1 to LPS stimulated neutrophils resulted in enhanced nuclear translocation of NF kappaB and increased production of the proinflammatory cytokines IL 1beta , Tnf alpha , and Mip 2 . uPA and the kringle domain ( KD ) of uPA potentiated cytokine expression and NF kappaB activation by neutrophils cultured with LPS , and had additive effects when combined with PAI 1 . ^^^ The c Jun N terminal kinase ( JNK ) was activated after exposure of resting neutrophils to PAI 1 or the uPA KD . ^^^ Enhanced JNK activation , but not that of other kinases induced by LPS , was present in neutrophils cocultured with PAI 1 or uPA KD . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Generation of angiostatin by platelet membranes was not affected by a matrix metalloproteinase ( MMP ) inhibitor , phenanthroline , but was inhibited by serine proteinase inhibitors aprotinin , leupeptin , plasminogen activator inhibitor 1 , and selective inhibitor of urokinase plasminogen activator ( uPA ) , uPA STOP ( TM ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The functions of the serpin PAI 1 ( plasminogen activator inhibitor 1 ) are based on molecular interactions with its target proteases uPA and tPA ( urokinase type and tissue type plasminogen activator respectively ) , with vitronectin and with endocytosis receptors of the low density lipoprotein family . ^^^ The peptide with an N terminal biotin inhibited the binding of the uPA PAI 1 complex to the endocytosis receptors low density lipoprotein receptor related protein 1A ( LRP 1A ) and very low density lipoprotein receptor ( VLDLR ) in vitro and inhibited endocytosis of the uPA PAI 1 complex in U 937 cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasmin , tissue plasminogen activator ( tPA ) , and urokinase plasminogen activator ( uPA ) activity , plasminogen activator inhibitor 1 ( PAI 1 ) , and alpha 2 antiplasmin ( alpha2AP ) antigen were measured in the AAA wall and juxtamural and luminal aspects of intraluminal thrombus in 18 patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
UPA , UPAR , ECE 1 , PAFAH1B1 , PGT , INOS , ENOS , TPA , ICAM 1 , VCAM 1 , PAI 1 , PAI 2 , VWF , PTGDR , F 3 , THBD ) , which was most evident after 24 hours . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MMP 2 and MMP 9 levels were examined using gelatin zymography and Western blotting ; their endogenous inhibitors , tissue inhibitor of metalloproteinase 2 ( TIMP 2 ) and tissue inhibitor of metalloproteinase 1 ( TIMP 1 ) , were assessed by Western blotting . uPA , uPAR and PAI 1 were examined using enzyme linked immunosorbent assay ( ELISA ) . ^^^ In rectal tumors , there was an increased activity of uPA compared with the activity in colon tumors ( P = 0 . 0266 ) , however urokinase type plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) showed no significant difference between colon and rectal cancer tissues . ^^^ CONCLUSION : These findings suggest that uPA may be expressed differentially in colon and rectal cancers , however , the activities or protein levels of MMP 2 , MMP 9 , TIMP 1 , TIMP 2 , PAI 1 and uPAR are not affected by tumor location in the colon or the rectum . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Over expression of uPA in the VTA induces doxycycline dependent expression of its receptor , uPAR , but not its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) . uPAR expression in the VTA is repressed upon silencing of uPA with lentiviruses expressing siRNAs . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer , is the plasminogen activation system that comprises of , among others , the urokinase Plasminogen Activator ( uPA ) and its main inhibitor , the Plasminogen Activator Inhibitor 1 ( PAI 1 ) . ^^^ In this study , we investigated the prognostic value of uPA and PAI 1 at the mRNA level in lymph node and hormone receptor positive breast cancer . ^^^ We investigated the prognostic value of uPA and PAI 1 at the mRNA level as measured by real time quantitative RT PCR . ^^^ RESULTS : uPA and PAI 1 gene expression was not found to be correlated with any of the established clinical and pathological factors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The catabolism of t PA was not inhibited by an excess of urokinase type plasminogen activator ( u PA ) , and t PA bound to Novikoff membranes was not complexed to PAI 1 , suggesting a mechanism independent of PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The parameters studied are cellular procoagulant activity , secretion of plasminogen activator inhibitor ( PAI 1 ) and urokinase type plasminogen activator ( u PA ) , activation and internalization of factor 10 and Merocyanine 540 staining . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Two plasminogen activators ( PAs ) : tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) , as well as the type 1 plasminogen activator inhibitor ( PAI 1 ) are synthesized and secreted by rat astrocytes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These complexes were probably formed by activation of urokinase type plasminogen activator ( u PA ) , and not tissue type plasminogen activator ( t PA ) , since SF levels of both u PA antigen and u PA plasminogen activator inhibitor ( PAI ) complexes were increased in 27 of the 42 patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tissue type plasminogen activator antigen ( t PA : Ag ) , urokinase type plasminogen activator antigen ( u PA : Ag ) , the proenzyme single chain u PA ( scu PA ) , and plasminogen activator inhibitor ( PAI ) were measured in the synovial fluid and plasma of 22 patients with seropositive rheumatoid arthritis ( RA ) , 13 with seronegative RA , and 23 patients with various forms of arthritis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Retinal pigment epithelial cells secrete urokinase type plasminogen activator and its inhibitor PAI 1 . ^^^ The results showed that these cells produce urokinase type plasminogen activator ( u PA ) and a plasminogen activator inhibitor ( PAI ) which is immunologically and biochemically similar to PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The assay is based on the quantitative conversion of PAI 1 to urokinase type plasminogen activator ( u PA ) PAI 1 complex the concentration of which is then determined by an ELISA employing monoclonal anti PAI 1 as catching antibody and monoclonal anti u PA as detecting antibody . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen , plasminogen activators ( PA ) , tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , alpha 2 antiplasmin ( alpha 2 AP ) , plasminogen activator inhibitor ( PAI ) , fibrinogen / fibrin degradation products ( FDP ) and D dimer were determined to elucidate the role of plasminogen activators and inhibitors in the pathogenesis of accelerated fibrinolysis in schistosomiasis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Co secretion of plasminogen activator inhibitor type 1 ( PAI 1 ) and urokinase type plasminogen activator was identified in short term cultures of primary type 2 pneumocytes isolated from adult rats . ^^^ Type 2 pneumocyte PAI 1 formed SDS resistant complexes with tissue type and urokinase type plasminogen activator and was found to be stable to acid , to short term exposure to heat , and to the denaturants guanidine HCl and SDS , while being sensitive to treatment with alkali and urea . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Other serine proteinases , e . g . urokinase type plasminogen activator and thrombin , also cleaved this `` substrate ' ' form of PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The aim of the present study was to compare plasma levels of urokinase type plasminogen activator ( u PA ) , before and after 20 min of venous stasis , with those of tissue type plasminogen activator ( t PA ) , type 1 plasminogen activator inhibitor ( PAI 1 ) and t PA / PAI 1 complexes , to determine whether both plasminogen activators and their inhibitor respond similarly to the same stimulus . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To determine the relationship between cardiovascular complications of estrogen therapy and fibrinolysis , fibrinolysis parameters plasminogen , urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) , were assessed in 12 prostatic cancer patients before and 6 weeks after the onset of estrogen therapy . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have previously reported that normal pleural leukocytes secrete a urokinase type plasminogen activator inhibitor ( PAI ) in culture . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The conditioned media from postsurgical Day 1 macrophage culture strongly inhibited urokinase type plasminogen activator ( PA ) and this plasminogen activator inhibitor ( PAI ) activities decreased following the extension of postsurgical time . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , it did not significantly modulate urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , plasminogen activator inhibitor ( PAI 1 ) , and tissue factor ( TF ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Vitronectin endows plasminogen activator inhibitor 1 ( PAI 1 ) , the fast acting inhibitor of both tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) , with additional thrombin inhibitory properties . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We measured antigen levels of 2 kinds of plasminogen activator , tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( UK ) , as well as those of their primary inhibitors , type 1 plasminogen activator inhibitor ( PAI 1 ) and type 2 plasminogen activator inhibitor ( PAI 2 ) , in tissue extracts from benign and malignant breast tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A decreased PAI expressed against tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) was found in lungs of all treated rats compared to controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 is a physiological inhibitor of both tissue type plasminogen activator and urokinase type plasminogen activator , key enzymes in the initiation of fibrinolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
On the reversible interaction of plasminogen activator inhibitor 1 with tissue type plasminogen activator and with urokinase type plasminogen activator . ^^^ The second order association rate constant ( k 1 ) of complex formation of recombinant two chain tissue type plasminogen activator ( rt PA ) or recombinant two chain urokinase type plasminogen activator ( rtcu PA ) by recombinant plasminogen activator inhibitor 1 ( rPAI 1 ) is 2 . 9 + / 0 . 4 10 10 ( 7 ) M 1 s 1 ( mean + / S . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( u PA ) antigen , tissue type plasminogen activator ( t PA ) antigen and activity , plasminogen activator inhibitor ( PAI ) type 1 antigen , PAI activity , antithrombin ( AT ) 3 activity , and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non sepsis patients with severe infectious disease . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We determined plasma levels of tissue type plasminogen activator ( t PA ) antigen , urokinase type plasminogen activator ( u PA ) antigen , and activity of the fast acting inhibitor of plasminogen activator ( PAI 1 ) in patients with different stages of liver cirrhosis ( Child A , B , and C ) and in age and sex matched healthy controls to investigate the contribution of the liver to the metabolism of these main components of the fibrinolytic system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of urokinase type plasminogen activator ( u PA ) and its type 1 inhibitor ( PAI 1 ) was examined in vivo in mouse wounds by in situ hybridization and immunohistochemistry . u PA mRNA was present in both basal and suprabasal keratinocytes in the regenerative epithelial outgrowths at the edge of the wounds . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We measured antigen levels of two kinds of plasminogen activators , tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( UK ) , as well as their primary inhibitor , type 1 plasminogen activator inhibitor ( PAI 1 ) in the tissue extracts of benign and malignant breast tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have studied the effect of plasminogen activator inhibitors PAI 1 and PAI 2 on the binding of urokinase type plasminogen activator ( u PA ) to its receptor in the human choriocarcinoma cell line JAR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The tissue specific distribution of tissue type and urokinase type plasminogen activator ( t PA and u PA ) and their inhibitor type 1 ( PAI 1 ) was analyzed at mRNA level in five major rat organ tissues . t PA mRNA was detected in lung , kidney , heart , and liver . u PA mRNA was detected in kidney and lung . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The PAI inhibited not only urokinase type plasminogen activator ( u PA ) but single and two chain tissue type plasminogen activators ( t PAs ) on plasminogen containing fibrin plate . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Corneal epithelial cells secrete tissue plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) and their inhibitor ( PAI ) , whereas these cell types in other tissues are known to secrete only u PA hitherto . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunol . , 71 : 215 223 ) and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 ( PAI 2 ) and of urokinase type plasminogen activator ( u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We studied the immunocytochemical localization of urokinase type plasminogen activator ( u PA ) and the type 1 plasminogen activator inhibitor ( PAI 1 ) in human fibroblasts and sarcoma cells , using both polyclonal and monoclonal antibodies . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Blood was collected at least 3 months after the last acute episode , and PAI 1 antigen and activity , as well as tissue type plasminogen activator ( t PA ) antigen , urokinase type plasminogen activator ( u PA ) antigen , and fibrinolytic activity were measured in these samples . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Highly purified plasminogen activator inhibitors of type 1 ( PAI 1 ) and type 2 ( PAI 2 ) , low Mr form , were compared with respect to their kinetics of inhibition of tissue type ( t PA ) and urokinase type plasminogen activator ( u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The granulosa cells of 49 follicles from 20 patients undergoing in vitro fertilization were obtained by laparoscopy and tested for the content of urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) and inhibitor of plasminogen activator ( PAI ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Mononuclear phagocytes are known to produce both urokinase type plasminogen activator ( u PA ) and a specific PA inhibitor , PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 inhibits both tissue type plasminogen activator and urokinase type plasminogen activator and may therefore be implicated in the control of various physiological processes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We therefore evaluated the mRNA levels for urokinase type plasminogen activator ( u PA ) , urokinase type plasminogen activator receptor ( u PAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) by using Northern blot analysis and in situ hybridization in four cases of GCT and spindle shaped mononuclear cells at the 35th passage from a GCT . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both neoantigenic epitopes were also exposed after complex formation between PAI 1 and either urokinase type plasminogen activator , plasmin or thrombin as well as after cleavage of the reactive site loop of non inhibitory substrate type PAI 1 variants . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have followed the synthesis and secretion of urokinase type plasminogen activator ( u PA ) and its inhibitor , PAI 1 , and matrix metalloproteinases ( MMPs ) and tissue inhibitor of metalloproteinases ( TIMP 1 ) during differentiation of a human osteoblastic cell line , HOS TE 85 , and the effect of TNF alpha on this process . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
At two to six hours stimulated expression of the genes encoding plasminogen activator inhibitor ( PAI 1 ) and platelet derived growth factor ( PDGF ) A chain was detected , but constitutive expression of urokinase type plasminogen activator ( u PA ) was not altered . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To evaluate the role of mesothelial cells ( MC ) in the high peritoneal fibrin turnover we investigated the expression of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) , and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha ( TNF alpha ) , interleukin 1 alpha ( IL 1 alpha ) , or bacterial lipopolysaccharide ( LPS ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Message levels of urokinase type plasminogen activator ( u PA ) and its inhibitor ( PAI 1 ) and heat shock protein ( HSP ) 70 are markedly raised 4 8 hours after wounding . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
On the other hand , the levels of 90K were positively correlated with those of cytosolic estrogen receptor , progesterone receptor , urokinase type plasminogen activator , its inhibitor PAI 1 , cathepsin D and PS 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To elucidate the pathophysiology of idiopathic pulmonary fibrosis ( IPF ) , we examined procoagulant ( tissue factor : TF ) , fibrinolytic ( tissue type plasminogen activator : t PA and urokinase type plasminogen activator : u PA ) and antifibrinolytic ( plasminogen activator inhibitor 1 : PAI 1 and PAI 2 ) activities in bronchoalveolar lavage ( BAL ) supernatant fluids and BAL cell lysates obtained from IPF patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Biological effects of disruption of the tissue type plasminogen activator , urokinase type plasminogen activator , and plasminogen activator inhibitor 1 genes in mice . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Since the plasminogen activator [ PA / plasminogen activator inhibitor ( PAI ) system is believed to be involved in a breakdown of articular cartilage in osteoarthritis ( OA ) , we studied the modulation of single components of the fibrinolytic system ( urokinase type plasminogen activator , u PA ; plasminogen activator inhibitor 1 , PAI 1 ; the surface receptor for u PA , u PAR ) in human chondrocytes in the presence of piroxicam . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We investigated immunohistochemically the localization of urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , plasmin inhibitor ( PI ) , and transforming growth factor beta ( TGA beta ) in tissue sections to examine the relationships between their localization and local invasiveness , tumor size and cervical lymph node metastasis of head and neck squamous cell carcinomas ( SCCs ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We examined the localization of urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitors ( PAI 1 and PAI 2 ) and plasminogen ( plg ) in 26 cases of colon cancer by immunohistochemical staining . ^^^ Localization of urokinase type plasminogen activator , plasminogen activator inhibitor 1 , 2 and plasminogen in colon cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , intra individual comparisons were made of the concentrations of t PA , urokinase type plasminogen activator ( u PA ) , PAI 1 , and PAI 2 in GCF from the same sites before and after periodontal treatment in eight healthy male volunteers aged 35 46 yr . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast to TNF alpha induced PAI 1 production , the transcription and synthesis of urokinase type plasminogen activator ( u PA ) was not inhibited by genistein . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasma D dimers ( one ELISA and two latex assays ) , fibrin monomer , prothrombin fragment 1 + 2 ( F1+2 ) , thrombin antithrombin 3 complex ( TAT ) and the t PA PAI 1 complex were all significantly correlated to the extension of DVT , whilst fibronectin , tissue type plasminogen activator ( t PA ) , single chain urokinase type plasminogen activator ( scru PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) were not . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
When mRNA obtained from RAECs cultured for 16 hours in serum free medium was analysed for the presence of specific messages of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) using human probes , weak specific binding could be seen for both t PA and mu PA while the PAI 1 probe gave a strong specific signal at 3 . 4 Kb and a weak signal at 2 . 3 Kb . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , no change in urokinase type plasminogen activator and plasminogen activator inhibitor 1 ( PAI 1 ) antigen synthesis was seen . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Human colorectal carcinogenesis has been shown previously to be associated with impressive changes in the tissue levels of plasminogen activators and their inhibitors , exemplified by an increase in the urokinase type plasminogen activator ( u PA ) and the inhibitors PAI 1 and PAI 2 , and a decrease in tissue type plasminogen activator ( t PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Incubation of PAI 1 P 12 , PAI 1 P 10 , or PAI 1 P 8 with a 2 fold molar excess of urokinase type plasminogen activator , plasmin , or thrombin also primarily generated a 41 kDa cleavage product ( 62 89 % ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Northern blot analysis showed that messenger ribonucleic acid specific for urokinase and plasminogen activator inhibitor 1 was present in colonic crypt cells and that expression over 18 hours of culture was increased 12 fold for urokinase type plasminogen activator and two to fourfold for the inhibitor compared with values found in autologous freshly isolated cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MAIN OUTCOME MEASURES Comparisons of concentrations of tissue plasminogen activator , urokinase type plasminogen activator , tissue plasminogen activator inhibitor 1 , cross linked fibrin degradation products , von Willebrand factor , and thrombin antithrombin 3 complexes in patients and controls at admission ; same comparisons in patients with silent ischaemia at the start of an episode and 10 minutes later . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both interferons caused a marked decrease in PAI 1 mRNA expression after 48 h with no change in urokinase type plasminogen activator ( u PA ) mRNA expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Parathyroid hormone ( PTH ) , prostaglandin E 2 , ( PGE 2 ) or tumor necrosis factor alpha ( TNF alpha ) enhanced the secretion of urokinase type plasminogen activator ( u PA ) antigen and suppressed the secretion of plasminogen activator inhibitor 1 ( PAI 1 ) antigen to the conditioned medium . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor type 1 ( PAI 1 ) , a member of the serpin family of serine protease inhibitors , inhibits both tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Zymographic analyses showed that tissue type plasminogen activator ( t PA ) occurred in association with casein micelles , partially as a complex with type 1 plasminogen activator inhibitor ( PAI 1 ) , whereas urokinase type plasminogen activator ( u PA ) was confined to milk leukocytes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Macrophage colony stimulating factor ( M CSF or CSF 1 ) and granulocyte macrophage CSF ( GM CSF ) have been shown to increase human monocyte urokinase type plasminogen activator ( u PA ) activity with possible consequences for cell migration and tissue remodeling ; because monocyte u PA activity is likely to be controlled in part also by the PA inhibitors ( PAIs ) made by the cell , the effect of M CSF and GM CSF on human monocyte PAI 2 and PAI 1 synthesis was investigated . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recent findings have elucidated the mechanism for clearance from the extracellular space of the two types of plasminogen activators , urokinase type plasminogen activator ( u PA ) and tissue type plasminogen activator ( t PA ) , and their type 1 inhibitor ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Quantitative zymography and enzyme linked immunosorbent assay were used to determine the amounts of urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator , and plasminogen activator inhibitors type 1 and type 2 ( PAI 1 and PAI 2 ) in benign and malignant primary brain tumors ( n = 28 ) as well as nonneoplastic brain ( n = 5 ) . u PA and PAI 1 antigen were undetectable in normal brain but significantly elevated in glioblastoma multiforme ( u PA , 2 . 86 + / 3 . 01 ng / mg ; PAI 1 , 8 . 19 + / 5 . 57 ng / mg ; P < 0 . 001 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tissue type plasminogen activator , urokinase type plasminogen activator , plasminogen activator inhibitor 1 , and plasminogen activator inhibitor 2 were also measured by means of enzyme linked immunosorbent assays . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
No significant changes in plasma D dimer and fibrinogen values were detected in the two groups . tPA , urokinase type plasminogen activator , PAI 1 and procoagulant activity were evaluated in vitro on cultured human endothelial cells and found to be unchanged following GM CSF addition . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Extrapolation of these in vitro results to periimplantational events in humans suggests that under progesterone regulation , decidual cell derived PAI 1 could 1 ) restrain blastocyst invasion of the stroma by inhibiting trophoblast associated urokinase type plasminogen activator , and 2 ) prevent hemorrhage during trophoblast invasion of the endometrial vasculature by inhibiting fibrinolysis mediated by tissue type plasminogen activator . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Blood samples were obtained on days 1 , 4 , and 7 after hospital admission to measure tissue type plasminogen activator antigen ( t PA ) , urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitor antigen ( PAI 1 ) , plasminogen , alpha 2 antiplasmin , fibrinogen , antithrombin 3 , protein C , protein S , thrombin antithrombin complexes ( TAT ) , D dimer , and von Willebrand factor related antigen ( vWF : Ag ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Mice with combined homozygous deficiency of tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) ( T U ) , of t PA and plasminogen activator inhibitor 1 ( PAI 1 ) ( T P ) , of u PA and PAI 1 ( U P ) or of t PA , u PA , and PAI 1 ( T U P ) were generated by inbreeding of mice with the respective deficiencies . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activity and antigen , euglobulin fibrinolytic activity , tissue type plasminogen activator activity and antigen urokinase type plasminogen activator antigen , plasminogen activator inhibitor 1 activity and antigen , plasminogen activator inhibitor 2 antigen , tissue type plasminogen activator / plasminogen activator inhibitor complexes , alpha 2 antiplasmin , histidine rich glycoprotein , and fibrinogen / fibrin degradation products were measured in blood samples taken from the umbilical vein of 100 healthy full term newborns . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Three enzyme linked immunosorbent assays for the quantitation of murine tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) , were developed using monoclonal antibodies raised against the autologous proteins in gene inactivated mice . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( u PA ) and the plasminogen activator inhibitor 1 ( PAI 1 ) are among the best second generation prognostic tissue factors in breast cancer . ^^^ Comparative study of four extraction procedures for urokinase type plasminogen activator and plasminogen activator inhibitor 1 in breast cancer tissues . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : Univariate analysis showed that a low tissue type plasminogen activator ( t PA ) activity in normal mucosa and in carcinomas and a high antigen level of inhibitor type 1 ( PAI 1 ) , and , to a lesser extent , of urokinase type plasminogen activator ( u PA ) receptor , in carcinomas are associated with a poor overall survival of the patients . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have investigated the localization of urokinase type plasminogen activator ( u PA ) , type 1 plasminogen activator inhibitor ( PAI 1 ) , u PA receptor ( u PAR ) and alpha ( 2 ) macroglobulin receptor / low density lipoprotein receptor related protein ( alpha ( 2 ) MR / LRP ) in human breast tumors by immunohistochemical methods . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We examined mRNA expressions of urokinase type plasminogen activator ( u PA ) , its specific receptor ( u PR ) , and plasminogen activator inhibitors ( PAI 1 and PAI 2 ) in 50 human breast cancers by the reverse transcriptase polymerase chain reaction method . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To further investigate possible involvement of the PA system , we quantified immunoreactive urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , both plasminogen activator inhibitors ( PAI 1 and PAI 2 ) and u PA receptor ( u PAR ) in synovial tissue extracts of 14 patients with rheumatoid arthritis ( RA ) and 12 with osteoarthritis ( OA ) . u PA , PAI 1 , PAI 2 and u PAR concentrations were significantly higher in RA than in OA patients . t PA antigen levels were significantly lower in RA than in OA synovial tissue extracts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : In patients undergoing gastric surgery for malignant ( n = 18 ) or benign ( n = 21 ) disorders . , blood drawn from the portal vein and a peripheral vein was analysed for tissue type plasminogen activator antigen and activity ( tPA : Ag , tPA : Act ) , single chain urokinase type plasminogen activator activity ( scuPA : Act ) , and plasminogen activator inhibitor antigen and activity ( PAI : Ag , PAI : Act ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Young and senescent cells were compared in quiescent and activated growth conditions for the secretion of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recently , generation of mice with single or combined deficiencies of main components of the fibrinolytic system , including plasminogen , tissue type and urokinase type plasminogen activator , plasminogen activator inhibitor 1 , and the cellular receptor for urokinase type plasminogen activator has allowed the role of the fibrinolytic system in vivo to be established more conclusively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Malignant tissue extracts had significantly higher levels of urokinase type plasminogen activator and plasminogen activator inhibitor 1 , but lower levels of tissue type plasminogen activator than normal mucosa . ^^^ Plasma levels of plasminogen activator inhibitor 1 antigen were significantly increased in cancer patients compared with controls , but there were no differences in tissue type and urokinase type plasminogen activator , in plasminogen activator inhibitor 2 , and D dimer levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Antigen levels of tissue plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitors type 1 ( PAI 1 ) and PAI 2 in GCF were determined with ELISAs and 17 beta oestradiol and progesterone in serum with radioimmunoassays . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study tissue plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) and PAI 1 were localized in arterial biopsies of healthy and atherosclerotic vessels by immunohistochemistry . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We examined the interference of endogenous inhibitors such as plasminogen activator inhibitor 1 ( PAI 1 ) and alpha 2 antiplasmin , and that of an endogenous activator namely single chain urokinase type plasminogen activator ( scu PA ) on the Coaset t PA assay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The increase seen for MCP 1 mRNA at 8 h was also observed for IL 8 mRNA but was not apparent for growth related gene expressions , urokinase type plasminogen activator ( u PA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The antigen levels of plasminogen activator inhibitor type 1 ( PAI 1 ) , plasminogen activator inhibitor type 2 ( PAI 2 ) , tissue type plasminogen activator ( t PA ) , and urokinase type plasminogen activator ( u PA ) were measured during pregnancy and severe preeclampsia . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The same concentrations of Dex led to a decrease in urokinase type plasminogen activator ( u PA ) synthesis and an increase in plasminogen activator inhibitor type 1 ( PAI 1 ) synthesis by SCC cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Renal biopsy tissue from 30 patients with MN along with specimens of normal kidney removed from six patients with renal tumors were examined for glomerular deposits of urokinase type plasminogen activator , tissue type plasminogen activator ( t PA ) , PAI 1 , VN , and fibrinogen by using immunofluorescence and immunoelectron microscopic techniques . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Detailed analysis of the reaction products formed during the interaction between PAI 1 and its target proteinases tissue type plasminogen activator ( t PA ) or urokinase type plasminogen activator ( u PA ) , in the presence of these monoclonal antibodies , revealed two distinct mechanisms of PAI 1 inactivation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Compared to the controls , plasma levels of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor ( PAI ) 1 antigen , D Dimer and enhanced thrombin generation were significantly ( P < 0 . 0001 ) increased in children with the common factor 5 mutation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Introduction of an RRHR motif into chicken urokinase type plasminogen activator ( ch uPA ) confers sensitivity to plasminogen activator inhibitor ( PAI ) 1 and PAI 2 and allows ch uPA mediated extracellular matrix degradation to be controlled by PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Wild type PAI 1 ( wtPAI 1 ) revealed the same conformational distribution pattern toward tissue type plasminogen activator ( t PA ) as toward urokinase type plasminogen activator ( u PA ) ( i . e . 53 + / 6 . 9 % active , 36 + / 6 . 8 % latent , and 12 + / 1 . 9 % substrate ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Increased expression of urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and collagenases in Caco 2 cells infected by Salmonella typhimurium . ^^^ Hypothesizing that the proteases might be provided by host cells , we investigated the changes of expression of urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and collagenases in epithelial cells ( Caco 2 ) infected with Salmonella typhimurium . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Using this approach , the expression of RNAs for tissue type plasminogen activator , urokinase type plasminogen activator , plasminogen activator inhibitor 1 , plasminogen activator inhibitor 2 , protease nexin , and urokinase receptor isoform 1 ( uPAR 1 ) were detected in mouse osteoclasts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen dependent and independent proteolytic activity of marine endothelioma ( End ) cells that were derived from mice with targeted inactivation of the tissue type plasminogen activator ( t PA / ) , urokinase type plasminogen activator ( u PA / ) or plasminogen activator inhibitor 1 ( PAI 1 / ) genes was studied with the use of fibrin and extracellular matrix degradation assays . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Molecular modeling techniques combined with recently acquired biochemical / biophysical data were used to provide insight into the stable complex formation between plasminogen activator inhibitor 1 ( PAI 1 ) and the target proteinases : tissue type plasminogen activator , urokinase type plasminogen activator , and thrombin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , we have significantly extended our earlier observations by identifying t PA variants that are substantially more resistant to inhibition by PAI 1 than any previously reported variants of t PA or urokinase type plasminogen activator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen system , via its triggers , tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) and its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) , has been implicated in thrombosis , arterial neointima formation , and atherosclerosis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( u PA ) system consists of the serine proteinases plasmin and u PA ; the serpin inhibitors alpha 2 anti plasmin , PAI 1 and PAI 2 ; and the u PA receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We measured the antigen levels of urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) in tissue extracts from nasopharyngeal carcinomas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Aortic SMC were isolated from transgenic mice showing single inactivations of the t PA , u PA , plasminogen activator inhibitor 1 , or urokinase type plasminogen activator receptor ( u PAR ) genes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary physiological inhibitor of both tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary physiological inhibitor of both tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : We examined the patterns of expression of urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and vitronectin in head and neck squamous cell carcinomas using immunohistochemical techniques . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Components of the coagulation ( thrombin antithrombin complexes , prothrombin fragment F 1 + 2 , activated factor 7 , and factor 7 antigen ) and fibrinolytic ( fibrin split product D dimer , plasmin plasmin inhibitor complex , tissue type plasminogen activator , urokinase type plasminogen activator , and plasminogen activator inhibitor 1 ) systems and markers of endothelial cell perturbation / dysfunction ( von Willebrand factor and thrombomodulin ) were measured before the start of infusion and after 2 , 6 , 12 , and 24 hours . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We therefore investigated the inhibitory effect of TNP 470 on cancer cell proliferation , and the suppressive effect of TNP 470 on urokinase type plasminogen activator ( u PA ) and its inhibitor ( PAI 1 ) , in human lung cancer cell lines in vitro . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The relative distribution of urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) was studied in cultured human gingival fibroblasts , healthy gingival tissues and inflamed gingival tissues by immunohistochemistry . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To evaluate the association among known angiogenic growth factors or factors related to the plasminogen activation system and clinicopathological factors in patients with colorectal cancer , we examined the expression of vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , transforming growth factor alpha ( TGF alpha ) , urokinase type plasminogen activator ( u PA ) , u PA receptor ( u PA R ) and plasminogen activator inhibitor 1 ( PAI 1 ) in clinical specimens of colorectal cancers by Northern blot analysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We compared the fibrinolytic activities of IVEC and HUVEC , and observed that IVEC express a more profibrinolytic phenotype than HUVEC , since they bind and activate plasminogen more efficiently , produce more tissue plasminogen activator and urokinase type plasminogen activator antigens , and secrete less plasminogen activator inhibitor 1 antigen both under basal conditions and after stimulation with lipopolysaccharide , phorbol ester and tumor necrosis factor . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Bovine mammary epithelial ( BME UV 1 , clone E T and BME UV , clone E T 2 ) and myoepithelial ( BMM UV , clone m T 2 ) cell lines were used to study the modulation of cell associated activity of urokinase type plasminogen activator ( u PA ) , as well as mRNA transcripts of u PA , its receptor ( u PAR ) , and inhibitors ( PAI 1 and PAI 2 ) during the cell cycle . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS AND RESULTS : Samples acquired by directional coronary atherectomy from 25 patients with type 2 diabetes and 18 patients without diabetes were characterized qualitatively histologically for cellularity and by immunohistochemistry visually and qualitatively and by quantitative image analysis for assessment of urokinase type plasminogen activator ( u PA ) and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To investigate a potential physiological role of the plasminogen / plasmin system in activation of the matrix metalloproteinase ( MMP ) system , the distribution of latent and active MMP 2 ( gelatinase A ) or MMP 9 ( gelatinase B ) was monitored in aorta extracts and in serum free conditioned cell culture medium obtained from wild type ( WT ) mice and from mice with deficiency of tissue type plasminogen activator ( t PA ( / ) ) , urokinase type plasminogen activator ( u PA ( / ) ) , plasminogen activator inhibitor 1 ( PAI 1 ( / ) ) or plasminogen ( Plg ( / ) ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Leukaemic and normal bone marrow samples were compared in terms of their content of the fibrinolytic agents , tissue plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) and their inhibitors . plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Production of urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) in human brain tumours . ^^^ The amounts of urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , and plasminogen activator inhibitor 1 ( PAI 1 ) , and the activity of u PA and t PA were determined by enzyme linked immunosorbent assay ( ELISA ) , and u PA and PAI 1 were immunolocalized using monoclonal antibodies in human brain tumours and normal brain tissues . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study , we determined the plasma and tissue concentrations of tissue type plasminogen activator , urokinase type plasminogen activator , plasminogen activator inhibitor 1 , plasminogen activator inhibitor 2 and urokinase type plasminogen activator receptor in 32 patients with pathology proved gastric cancer . ^^^ Plasma plasminogen activator inhibitor 1 was significantly higher in gastric cancer than in benign gastric disease ( p < 0 . 0005 ) , whereas plasma urokinase type plasminogen activator was significantly lower in patients with gastric cancer than in those with benign ulcer ( p = 0 . 003 ) . ^^^ The plasma and tissue levels of fibrinolytic parameters were not affected by tumor size or distant metastasis , whereas tumor tissue concentration of urokinase type plasminogen activator receptor and plasminogen activator inhibitor 2 were significantly higher in N 0 than in N 1 and N 2 , and tissue plasminogen activator inhibitor 1 was significantly higher in N 0 than in N 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of urokinase type plasminogen activator ( u PA ) , u PA receptor ( u PAR ) and plasminogen activator inhibitor ( PAI ) 1 and 2 was examined in 105 cases of primary lung cancer tissue using immunohistochemical staining and reverse transcriptase polymerase chain reaction ( RT PCR ) techniques . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The binding of VEGF B to its receptor on endothelial cells leads to increased expression and activity of urokinase type plasminogen activator and plasminogen activator inhibitor 1 , suggesting a role for VEGF B in the regulation of extracellular matrix degradation , cell adhesion , and migration . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The tissue concentrations of urokinase type plasminogen activator ( u PA ) , urokinase type plasminogen activator receptor ( u PAR ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and tissue type plasminogen activator ( t PA ) were investigated by an ELISA technique in normal and malignant samples of the prostate from 24 patients undergoing radical prostatectomy for organ confined prostate cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , plasma levels of tissue type plasminogen activator and urokinase type plasminogen activator are significantly higher in the hemolytic uremic patients than in those with acute renal failure of other causes ( P < 0 . 01 and P < 0 . 05 respectively ) . ( 4 ) Hemodialysis leads to an increase in tissue type plasminogen activator antigen and a decrease of plasminogen activator inhibitor 1 activity levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both the urokinase type plasminogen activator receptor ( uPAR ) and the plasminogen activator inhibitor 1 ( PAI 1 ) are thought to be important factors in this system . ^^^ Urokinase type plasminogen activator receptor mRNA , PAI 1 mRNA , uPAR and PAI 1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci . ^^^ Expression of urokinase type plasminogen activator receptor and plasminogen activator inhibitor 1 in gastric cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The aim of our study was to measure fibrinogen and fibrin degradation products ( D dimer ) , interleukin 6 tissue plasminogen activator , plasminogen activator inhibitor 1 and urokinase type plasminogen activator in the plasma and arterial walls of 45 patients who had arterial surgery between April 1993 and November 1995 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
F 3 fraction enhanced mRNA expression of urokinase type plasminogen activator ( u PA ) , matrix metalloproteinase 2 ( MMP 2 ) , and membrane type MMP ( MT MMP ) in CPAE cells whereas the expression of plasminogen activator inhibitor 1 ( PAI 1 ) mRNA was not changed . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Metastatic conversion correlated with upregulation of urokinase type plasminogen activator receptor RNA expression and downregulation of plasminogen activator inhibitor 1 , collagen alpha 1 ( 1 ) , and cytokeratin 14 ( K 14 ) RNA expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : Human mesothelial cells ( HMCs ) have an important role in maintaining an adequately functioning fibrinolytic system in the peritoneal cavity by secreting the fibrinolytic enzymes tissue type and urokinase type plasminogen activator ( t PA and u PA ) , as well as a specific PA inhibitor , PA inhibitor type 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
DESIGN AND METHODS : Samples of stimulated conditioned media were collected over a period of 24 hours to determine : plasminogen activator ( PA ) and plasminogen activator inhibitor ( PAI ) activity , PAI 1 mRNA , tissue type plasminogen activator ( t PA ) antigen and urokinase type plasminogen activator ( u PA ) antigen . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , or plasminogen activator inhibitor 1 ( PAI 1 ) ( u PA / , t PA / or PAI 1 / , respectively ) or of their wild type controls ( u PA+ / + , t PA+ / + or PAI 1+ / + ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : High levels of urokinase type plasminogen activator ( u PA ) were demonstrated in gastric carcinomas along with inhibitors of plasminogen activators ( PAI 1 and PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We examined the effect of pH on the extraction of urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) from paranasal sinus mucous membrane associated with chronic sinusitis and antrochoanal polyps . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( u PA ) and tissue type plasminogen activator ( t PA ) play important roles in fibrinolysis , cell migration , tissue destruction , angiogenesis and tissue remodeling . u PA and t PA activity in tissue are tightly regulated by plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The mediators of the plasminogen activator system , namely urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) , are a key complex involved in fibrinolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cell conditioned medium was assayed for tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) by enzyme linked immunosorbent assay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) functions as an important regulator of fibrinolysis by inhibiting both tissue type and urokinase type plasminogen activator . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) functions as an important regulator of fibrinolysis by inhibiting both tissue type and urokinase type plasminogen activator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Of the genes studied , urokinase type plasminogen activator and plasminogen activator inhibitor 1 were regulated in RPE cells similar to fibroblasts at senescence . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The antigen of urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) were measured by ELISA , and u PA activity was evaluated by electrophoretic enzymography . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Vascular endothelial cells ( ECs ) modulate the blood fibrinolytic system by secreting tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , and their inhibitor , type 1 plasminogen activator inhibitor ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This indicated that the inhibitory activity of PAI 1 was required for its anti apoptotic effect but the urokinase type plasminogen activator receptor was not involved . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Proteins influencing plasminogen activation to plasmin , namely plasminogen activators tissue type plasminogen activator ( t PA ) and urokinase type plasminogen activator ( u PA ) and their principal inhibitors , plasminogen activator inhibitor 1 ( PAI 1 ) and PAI 2 , were measured in the plasma , the polymorph and mononuclear cell fractions taken from patients with major sepsis who were entering a general intensive care unit . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunofluorescence and quantitative immunofluorescence with antibodies against alpha smooth muscle actin , desmin , matrix metalloproteinases 2 ( MMP 2 ) , MMP 9 , tissue inhibitor of metalloproteinases 1 ( TIMP 1 ) and 2 ( TIMP 2 ) , urokinase type plasminogen activator ( u PA ) and its inhibitor 1 ( PAI 1 ) were studied with confocal microscopy . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The balance between urokinase type plasminogen activator and plasminogen activator inhibitor 1 is modified ; RNA and catalytic activity for the former are elevated while PAI 1 RNA is reduced . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The interaction of fibrinolytic components with GPIb / V / IX of platelets on thrombus formation , was investigated in mice deficient in tissue type ( tPA / ) , urokinase type plasminogen activator ( uPA / ) or plasminogen activator inhibitor 1 ( PAI 1 / ) and in their wild type control ( tPA+ / + , uPA+ / + , PAI 1+ / + ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In vivo tumor progression in mice with targeted deficiencies in urokinase type plasminogen activator ( UPA / ) and its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 / ) , was studied using a fibrosarcoma tumor model . ^^^ Tumor development is retarded in mice lacking the gene for urokinase type plasminogen activator or its inhibitor , plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
There was no difference in the levels of urokinase type plasminogen activator , plasminogen activator inhibitor 1 and 2 , tissue inhibitor of metalloproteinases 2 or vascular endothelial growth factor . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These cells showed reduced invasiveness that paralleled decreased mRNA levels of urokinase type plasminogen activator and its receptor , tissue type plasminogen activator , and plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Furthermore , the PAI 1 activity toward urokinase type plasminogen activator and tissue type plasminogen activator was significantly prolonged in the presence of alpha ( 1 ) acid glycoprotein . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Here , we show that the physiological inhibitor of urokinase type plasminogen activator , PAI 1 , is also induced by MNNG in a p 53 dependent fashion , because MNNG induced PAI 1 in p 53 expressing cells but not in p 53 / cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunohistochemical analyses of the healing tissues and an analysis of the periodontal wound healing fluid by ELISA were carried out for the detection of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , and 2 plasminogen activator inhibitors ( PAI 1 and PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
At the cellular level , particulate nickel subsulfide inhibits fibrinolysis by transcriptionally inducing expression of plasminogen activator inhibitor ( PAI ) 1 , an inhibitor of the urokinase type plasminogen activator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
EXPERIMENTAL DESIGN : Antigen levels of urokinase type plasminogen activator , plasminogen activator inhibitor 1 ( PAI 1 ) , Cathepsins B , D , and L were determined using immunochemical assays in primary tumor tissue of 276 patients . ^^^ Prognostic impact of proteolytic factors ( urokinase type plasminogen activator , plasminogen activator inhibitor 1 , and cathepsins B , D , and L ) in primary breast cancer reflects effects of adjuvant systemic therapy . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We observed a preferential expression of MAGE A in patients at a higher risk of recurrence : those harboring tumors with high levels of the protease urokinase type plasminogen activator and its inhibitor plasminogen activator inhibitor 1 , high score of the Ki 67 proliferation antigen , and lesser degree of differentiation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type plasminogen activator , tissue type plasminogen activator , urokinase type plasminogen activator receptor , and plasminogen activator inhibitor 1 expression were studied . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The recombinant PAI 1 / GFP had significant inhibition activity on urokinase type plasminogen activator and displayed autonomous fluorescence . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have examined expression of the components of the plasminogen activation system in human astrocytoma U 373 MG cells and found that interleukin 1beta ( IL 1beta ) , tumour necrosis factor alpha TNF alpha ) , interferon gamma ( INF gamma ) and epidermal growth factor ( EGF ) specifically regulate the expression of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and protease nexin 1 ( PN 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In total , 22 functional and immunologic assays were applied to plasma obtained from domestic pigs , and the following blood coagulation and fibrinolysis variables were measured : prothrombin time , activated partial thromboplastin time , tissue factor , tissue factor pathway inhibitor , factor 7 , protein C , protein S , prothrombin fragment 1+2 , antithrombin , thrombin antithrombin complexes , fibrinogen , soluble fibrin , urokinase type plasminogen activator , plasmin inhibitor , plasminogen activator inhibitor 1 , and D dimer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Primary Breast Cancer , Urokinase Type Plasminogen Activator , Inhibitors The aim of the study was to monitor urokinase plasminogen activator antigen concentrations and its type 1 ( PAI 1 ) and type 2 ( PAI 2 ) inhibitors in histologically defined forms of primary breast cancer and a comparison with these antigens levels in normal tissue . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , the primary physiological inhibitor of both tissue type plasminogen activator and urokinase type plasminogen activator in plasma , is a well established risk factor in thrombotic diseases . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) , the primary physiological inhibitor of both tissue type plasminogen activator and urokinase type plasminogen activator in plasma , is a well established risk factor in thrombotic diseases . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 inhibits tissue plasminogen activator and urokinase type plasminogen activator , resulting in reduced plasminogen activity and attenuated fibrinolysis and proteolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The neutralization of positively charged Arg residues in this cluster decreases the affinity of scu PA and the double chain urokinase type plasminogen activator for PAI 1 , which results in an enhancement of the stability in plasma and the fibrinolytic efficiency of the activator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULTS : Expression of matrix metallsoproteinase ( MMP ) 2 , MMP 9 , tissue inhibitor of metalloproteinases ( TIMP ) 1 and urokinase type plasminogen activator ( u PA ) , other than that of TIMP 2 and plasminogen activator inhibitor type ( PAI ) 1 , was observed in normal trophoblastic cells in in vitro culture . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have compared the effects of maspin with those of PAI 1 in a range of situations in which plasminogen activation is potentiated , reflecting the biological context of this proteolytic system : urokinase type plasminogen activator bound to its receptor on the surface of tumor cells , tissue type plasminogen activator specifically bound to vascular smooth muscle cells , fibrin , and the prion protein . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Hormone receptor status , Ki 67 , S phase fraction , DNA ploidy , HER 2 / neu , p 53 , epidermal growth factor receptor , urokinase type plasminogen activator , plasminogen activator inhibitor 1 , bone marrow micrometastases as well as patient age , menopausal status , tumor site , tumor size , histologic type , tumor grade , carcinoma in situ , multifocality , and lymph vascular invasion ( LVI ) were studied to predict axillary lymph node status . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is a factor in urokinase type plasminogen activator proteolytic system , which is important for tumour invasion and metastasis . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is a factor in urokinase type plasminogen activator proteolytic system , which is important for tumour invasion and metastasis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Western blot analyses using antibodies against hepatocyte growth factor , hepatocyte growth factor receptor , phosphotyrosine , hepatocyte growth factor activator , urokinase type plasminogen activator receptor , urokinase type plasminogen activator , plasminogen activator inhibitor 1 , fibrinogen and plasmin were performed on membrane enriched fractions from the frozen tissue , as was collagen zymography for matrix metalloproteinase 2 and matrix metalloproteinase 9 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of factors of the urokinase type plasminogen activation system , including the urokinase type plasminogen activator ( u PA ) and the plasminogen activator inhibitor type 1 ( PAI 1 ) , which have been described to be frequently implicated in the process of degradation of the extracellular matrix during the metastatic process , were also analyzed . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In vascular injury models , Serp 1 altered early cellular plasminogen activator ( tissue plasminogen activator ) , inhibitor ( PAI 1 ) , and receptor ( urokinase type plasminogen activator ) expression ( p < 0 . 01 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
During incubation with urokinase type plasminogen activator , the polymers were slowly converted to reactive centre cleaved monomers , indicating substrate behaviour of the terminal PAI 1 molecules in the polymers . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The purpose of this study was to investigate the association between tumor tissue levels of total tissue inhibitor of metalloproteinases 1 ( TIMP 1 ) and prognosis in patients with primary breast cancer and to analyze whether measurement of TIMP 1 in tumor extracts added prognostic information to that obtained from measurements of urokinase type plasminogen activator and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The serpin plasminogen activator inhibitor 1 ( PAI 1 ) is a fast and specific inhibitor of the plasminogen activating serine proteases tissue type and urokinase type plasminogen activator and , as such , an important regulator in turnover of extracellular matrix and in fibrinolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : To quantify the ex vivo production of proangiogenic proteins ( vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( tPA ) ) and angiogenesis inhibitors ( plasminogen activator inhibitor type 1 ( PAI 1 ) and angiostatin ) from epithelial and stromal components of primary prostate cancer ( CaP ) and benign prostatic hyperplasia ( BPH ) cultures . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tissue specimens from eight patients with failing or failed infra inguinal vein bypasses and three specimens from normal veins were harvested to study urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) by in situ hybridization and immunohistochemistry . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasma levels of the thrombin activation system ( thrombin antithrombin complex [ TAT ] , tissue factor pathway inhibitor [ TFPI ] , and prothrombin fragments 1+2 [ F1+2 ] ) and plasmin activation system ( tissue and urokinase type plasminogen activator [ t PA and u PA ] , plasminogen activator inhibitor 1 [ PAI 1 ] , and D dimer ) were measured with enzyme linked immunosorbent assay kits before angiography . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
INTERVENTIONS : We characterized the expression of tissue type and urokinase type plasminogen activator ( t PA and u PA ) as well as plasminogen activator inhibitor ( PAI ) 1 and PAI 2 in human endothelial cells ( EC ) from the microvascular pulmonary circulation ( HMVEC L ) and compared it with that of EC from pulmonary artery ( HPAEC ) and umbilical vein ( HUVEC ) under baseline conditions and upon stimulation with either tumor necrosis factor alpha or lipopolysaccharide . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study of nasal mucosa , we investigated the presence of mRNA of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and plasminogen activator inhibitor 2 ( PAI 2 ) using reverse transcription polymerase chain reaction ( RT PCR ) and in situ hybridization , and compared these results with their localization in immunostained tissues . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : Serial bronchoalveolar lavage fluid ( BALF ) samples were assayed for prothrombin activation fragment ( F1+2 ) , thrombin antithrombin ( TAT ) complex , fibrinolytic activity , urokinase type plasminogen activator ( u PA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) on days 1 , 4 , and 7 after VAP onset . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Supernatant prostaglandin E 2 and mRNA expressions of COX 2 , vascular endothelial growth factor ( VEGF ) , urokinase type plasminogen activator ( u PA ) , u PA receptor , plasminogen activator inhibitor type 1 ( PAI 1 ) , and PAI 2 were measured . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 , the physiological inhibitor of tissue type and urokinase type plasminogen activator , is a unique member of the serpins as it exists in three distinct conformations : an active inhibitory conformation , a non inhibitory substrate conformation , and a non reactive latent conformation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is an important component of the plasminogen / plasmin system as it is the main inhibitor of tissue type and urokinase type plasminogen activator . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is an important component of the plasminogen / plasmin system as it is the main inhibitor of tissue type and urokinase type plasminogen activator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Binding of vitronectin to NBD P 9 PAI 1 does not affect SI but results in a 2 . 0 6 . 5 fold decrease in the limiting rate constant ( klim ) of RCL insertion for urokinase type plasminogen activator at pH 6 . 2 8 . 0 and for tissue type plasminogen activator at pH 6 . 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activation system was also altered in tumors with a decrease of urokinase type plasminogen activator ( u PA ) and tissue type plasminogen activator ( t PA ) and a strong increase of plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
NSO produced a concentration dependent inhibition of tissue type plasminogen activator ( t PA ) , urokinase type plasminogen activator ( u PA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , fluorescence activated cell sorting analysis revealed a 25 % increase in cell surface u PAR in hr sMTf treated HMEC 1 , whereas the binding of the urokinase type plasminogen activator ( u PA ) * plasminogen activator inhibitor 1 ( PAI 1 ) complex is decreased . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A critical review of classical and newer individual molecular markers , such as hormone receptors , HER 2 , urokinase type plasminogen activator and plasminogen activator inhibitor 1 , cyclin E , topoisomerase 2 , and p 53 , was performed , and the preliminary results obtained using the new gene expression profiling technology are described along with their potential clinical implications . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Messenger RNA levels of tissue type plasminogen activator , urokinase type plasminogen activator , and plasminogen activator inhibitor 1 were analysed using Taqman real time reverse transcriptase polymerase chain reaction and protein release by enzyme linked immunosorbent assay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OE DEP and OE UFP exposure reduced plasminogen activator inhibitor 1 ( PAI 1 ) production by the cells but did not affect the production of thrombomodulin , tissue type plasminogen activator , or urokinase type plasminogen activator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition , the expressions of molecules involved in MMP activating and inhibitory pathways ( urokinase type plasminogen activator and tissue type plasminogen activator ; TIMP 1 , TIMP 2 , and plasminogen activator inhibitor 1 ) were found to be increased after abdominal irradiation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
BACKGROUND : The prognostic relevance of urokinase type plasminogen activator ( u PA ) , u PA receptor ( u PAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) in gastric carcinoma was demonstrated in an independent patient series . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , in renal carcinoma cells that constitutively express HIF 1alpha and HIF 2alpha due to loss of VHL function , we found that high basal VEGF , glucose transporter 1 , urokinase type plasminogen activator receptor , and plasminogen activator inhibitor 1 expression was predominantly dependent on HIF 2alpha . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor ( PAI 1 ) is an important component of the plasminogen / plasmin system as it is the main inhibitor of tissue type ( t PA ) and urokinase type plasminogen activator ( u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Excess of the amino terminal fragment of u PA ( ATF ) completely blocked the specific binding of [ 125I ] u PA , confirming that the binding of u PA was independent of the presence of the active site and / or of the formation of complexes with PAI 1 . 3H thymidine incorporation by mesangial cells after stimulation with 100 nM active u PA showed that u PA had a moderate but significant mitogenic effect , in contrast to inactive u PA and ATF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
At rest , heparin and Org 10172 did not influence the plasma concentrations of endogenous t PA antigen and activity , urokinase type PA ( u PA ) antigen , plasmin activatable pro urokinase ( scu PA ) , active urokinase ( tcu PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) antigen . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of tissue plasminogen activator ( t PA ) , urokinase plasminogen activator ( u PA ) and plasminogen activator inhibitor ( PAI 1 ) have been determined in endometrial curettings obtained from 46 subfertile women during proliferative , early or late secretory phases of the menstrual cycle . t PA activity and antigen concentrations was significantly higher ( P < 0 . 001 ) in late secretory endometrium than in proliferative or early secretory endometrium . ^^^ However , u PA concentration was not significantly different and no PAI activity could be demonstrated in the menstrual phases studied . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tissue plasminogen activator ( t PA ) , urokinase plasminogen activator ( u PA ) and plasminogen activator inhibitors ( PAI ) are elevated in late pregnancy with t PA and u PA remaining so at 6 weeks postnatal . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Conversion of single chain to two chain forms of u PA or inhibition of active two chain forms with plasminogen activator inhibitor 1 or with the active site serine inhibitor phenyl methyl sulfonyl fluoride , did not alter the reactivity in the assay . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasma levels of plasminogen activators ( t PA , u PA ) and their inhibitor ( PAI 1 ) were studied in patients suffering from Buerger ' s disease and healthy volunteers before and after 15 minutes of venous occlusion test . ^^^ On the contrary patients with Burger ' s disease showed a marked increase in u PA antigen concentrations with concomitant decrease in PAI 1 antigen levels . ^^^ In conclusion , Buerger ' s disease is associated with the endothelial derangement with increased u PA release and decreased PAI 1 release , which does not influence the function of fibrinolytic system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasma concentration of thrombin antithrombin 3 complex ( TAT ) , tissue type plasminogen activator ( t PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , PAI 2 , D dimer complex and urokinase plasminogen activator ( u PA ) activity were studied in 30 patients with acute nonlymphoblastic leukemia ( ANLL ) , before and during antileukemic therapy . ^^^ TAT increased significantly during the treatment period in all cases . u PA and PAI 1 levels were elevated but there were no statistically significant differences between patients with and without DIC . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The latter was associated with elevated FXII and PKK , while C 1 INH was decreased , ATIII and alpha 2M were unchanged ; it could not be accounted for by changes in t PA , u PA , PAI , plasminogen , alpha 2 AP , proteins C or S . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Measurements included t PA , u PA , PAI 1 , PAP ( as a measure of in vivo activation of fibrinolysis ) , FbDPs , FGN , vWF , and 8 : C . ^^^ RESULTS In both IDDM and control subjects , levels of t PA , u PA , PAP , vWF , and 8 : C continued to rise throughout the exercise , whereas PAI 1 showed a similar decline in both groups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have previously shown that alpha thrombin exerted a mitogenic effect on human glomerular epithelial cells and stimulated the synthesis of urokinase type ( u PA ) and tissue type plasminogen activator ( t PA ) and of their inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^ Conversely , nicardipine did not modify thrombin stimulated synthesis of u PA , t PA , and PAI 1 . ^^^ Simultaneous addition of these two thrombin derivatives had no effect on [ Ca2+ ] 1 , and 3H thymidine incorporation but stimulated u PA , t PA , and PAI 1 synthesis although to a lesser extent than alpha thrombin . ^^^ In conclusion , multiple signalling pathways can be activated by alpha thrombin in glomerular epithelial cells : 1 ) Ca2+ influx through a dihydroperidine sensitive calcium channel , which seems critical for mitogenesis ; 2 ) protein kinase C activation by phosphoinositide breakdown , which stimulates both mitogenesis and synthesis of u PA , t PA , and PAI 1 ; 3 ) protein kinase C activation by other phospholipid breakdown can stimulate u PA , t PA , and PAI 1 synthesis but not mitogenesis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Evidently due to elevated u PA activity PAI 1 was removed from the extracellular matrix more rapidly in TGF beta 1 treated cells than from control cultures . ^^^ Northern hybridization analysis of human keratinocytes showed that TGF beta 1 rapidly elevated both u PA and PAI 1 mRNA levels . ^^^ Comparison of the temporal induction profiles indicated that the mRNA for u PA increased more slowly but was more persistent than that of PAI 1 . ^^^ Actinomycin D inhibited the induction of both u PA and PAI 1 mRNA , suggesting that the induction was due to increased transcription . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of urinary type plasminogen activator ( u PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and PAI 2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues . ^^^ Levels of u PA , PAI 1 and PAI 2 were higher in cancer than in control tissues . ^^^ PAI 1 levels were higher together with the progression of cancer however there were no differences in u PA or PAI 2 levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is the principal inhibitor of the two activators of the fibrinolytic system : tissue and urokinase type PAs ( t PA and u PA ) . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the principal inhibitor of the two activators of the fibrinolytic system : tissue and urokinase type PAs ( t PA and u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TGF beta 1 also caused an increase of both u PA and PAI 1 antigens , while there was no detectable effect on t PA . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Zymographic analysis of secreted PA related compounds revealed production of free urokinase ( u PA ) and type 1 plasminogen activator inhibitor ( PAI 1 ) complexed to tissular plasminogen activator ( t PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We also find that transforming growth factor beta 1 ( TGF beta 1 ) , which in vitro modulates a number of endothelial cell functions relevant to angiogenesis , also increases both PAI 1 and urokinase type PA ( u PA ) mRNA . ^^^ However , the kinetics and amplitude of PAI 1 and u PA mRNA induction by these agents are strikingly different . ^^^ We have used the ratio of u PA : PAI 1 mRNA levels as an indicator of proteolytic balance . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We used the amnion invasion assay to investigate whether monocyte invasiveness is affected by matrix bound plasminogen activator inhibitors ( PAI ) and by fluid phase u PA . ^^^ Finally , the inhibitory action of matrix bound PAI 1 can be abrogated by addition of 5 IU / ml u PA to the monocytes in the invasion chamber . ^^^ These findings indicate that monocyte invasiveness might be regulated not only by expression and occupation of u PA R but also by matrix bound PAI 1 . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The authors examined the effect of insulin like growth factor 1 ( IGF 1 ) , epidermal growth factor ( EGF ) , and acidic fibroblast growth factor ( AFGF ) on the synthesis by human retinal endothelial cell ( HREC ) of plasminogen activators ( PA ; tissue type [ t PA ] and urokinase type [ u PA ] ) and plasminogen activator inhibitor ( PAI ) . ^^^ Immunologic and functional assays for t PA , u PA , and PA 1 were conducted with cell lines derived from three diabetics and three nondiabetic controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor type 1 ( PAI 1 ) , the fast acting inhibitor of tissue type plasminogen activator ( t PA ) and urokinase ( u PA ) , is a member of the serpin superfamily of proteins . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Type 1 PAI ( PAI 1 ) is the physiological inhibitor both of urinary type PA ( u PA ) and tissue type PA ( t PA ) ( Loskutoff et al . , 1989 ) and is a major component of the ECM of cultured cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) , an essential regulatory protein of the fibrinolytic system , harbors interaction sites for plasminogen activators ( tissue type [ t PA ] and urokinase type [ u PA ] ) and for fibrin . ^^^ We propose that , upon activation of platelets , PAI 1 is fixed within the clot by binding to fibrin and retains its full capacity to inhibit t PA and u PA . . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) , an essential regulatory protein of the fibrinolytic system , harbors interaction sites for plasminogen activators ( tissue type [ t PA ] and urokinase type [ u PA ] ) and for fibrin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is the fast acting inhibitor of both tissue type and urokinase type plasminogen activators ( t PA , u PA ) and is an essential regulatory protein of the fibrinolytic system . ^^^ To assess whether these cofactors turn PAI 1 into a general protease inhibitor or whether their influence is restricted to thrombin , the second order association rate constants between PAI 1 and the human plasma proteases t PA , u PA , plasmin , thrombin , Factor Xa ( FXa ) , and Factor XIIa ( FXIIa ) in the absence and in the presence of either vitronectin or heparin are determined . ^^^ In addition , vitronectin moderately increases the rate of inhibition by PAI 1 of u PA and of plasmin , but does not alter the rate of inhibition of t PA , FXa , or FXIIa ; ( 3 ) Apart from the important role of the P 1 residue , no consensus can be presented on the nature of other residues within the P 3 to P 3 ' region with regard to target protease specificity . . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the fast acting inhibitor of both tissue type and urokinase type plasminogen activators ( t PA , u PA ) and is an essential regulatory protein of the fibrinolytic system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Inasmuch as the mesothelial cells also released plasminogen activator inhibitor 1 , as do human umbilical vein endothelial cells , we could not detect u PA activity in culture medium . u Pa may play a role in the protection against adhesion among visceral organs . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrinolytic system components like tissue plasminogen activators ( t PA ) , and urokinase ( u PA ) , and their inhibitors PAI 1 and PAI 2 were all studied . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The effects of VEGF , a recently described angiogenic factor , were assessed on PA activity and PA and PAI 1 mRNA levels in microvascular endothelial cells . u PA and t PA activity were increased by VEGF in a dose dependent manner , with maximal induction at 30 ng / ml . u PA and t PA mRNAs were increased 7 . 5 and 8 fold respectively after 15 hours , and PAI 1 mRNA 4 . 5 fold after 4 hours exposure to VEGF . ^^^ At equimolar concentrations ( 0 . 5 nM ) , VEGF was a more potent inducer of t PA mRNA than bFGF , while bFGF was a more potent inducer of u PA and PAI 1 mRNAs . ^^^ In addition , VEGF induced u PA and PAI 1 mRNAs with kinetics similar to those previously demonstrated for bFGF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The apparent difference in u PA activity and antigen levels of these two lines was not due to the difference in the production of plasminogen activator inhibitor ( PAI ) , because PAI antigen level and PAI activity in the culture media were almost equal between them . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activators t PA , u PA and its inhibitor ( PAI ) in normal males and females . ^^^ We determined the plasma levels of tissue plasminogen activator ( t PA ) , plasminogen activator inhibitor ( PAI ) activity and their antigen levels including urokinase plasminogen activator ( u PA ) in 33 male and 27 female normal subjects . ^^^ This study demonstrates that significant differences in t PA , u PA and PAI exist between male and female subjects which should be taken into account when determining their levels in clinical conditions . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Ethanol at both concentrations induced after 30 days a decreased PAI in the pyloric region and the body of the stomach , which was expressed against u PA , but not against t PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Binding of [ 125I ] t PA PAI 1 complex was unaffected by high concentrations of unlabelled t PA , PAI 1 , u PA or u PA PAI 1 complex ; only t PA PAI 1 complex competed for binding . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the presence of a molar excess of anti plasminogen activator inhibitor type 1 ( PAI 1 ) antibodies the interiorization rate is similar to that observed with catalytically inhibited u PA , suggesting that PAI 1 molecules can modulate the intracellular accumulation of u PA in this cell line . ^^^ We conclude that cell surface associated u PA modulation in human keratinocytes involves ligand binding , uptake , and degradation , mediated by the classic receptor system for u PA A chain , which can be modulated by membrane associated PAI 1 molecules . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We analyzed the effect of IL 1 on the synthesis of collagenase , stromelysin , and tissue inhibitor of metalloproteases ( TIMP ) in human cartilage explants and culture chondrocytes , as well as its effect on the secretion of plasminogen activators ( t PA , u PA ) and inhibitors ( PAI 1 , PAI 2 ) in cartilage explants . ^^^ The increase in t PA synthesis was accompanied by a decreased PAI 1 level , while the PAI 2 level remained unchanged . u PA could not be detected in the culture medium . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We conclude that increased levels of PAI 1 in malignant tissue of the stomach and colorectal tract may serve to modulate extra cellular proteolysis by u PA . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
U PA was determined by a competition RIA , t PA by an ELISA and PAI by a spectrophotometric assay . 15 patients showed normozoospermia , 11 azoospermia and 41 oligoasthenoteratozoospermia ( OAT syndrome ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These latter cell lines also produced plasminogen activator inhibitor type 1 ( PAI 1 ) and type 2 ( PAI 2 ) mRNA and protein . u PA receptor ( u PA R ) mRNA and binding of radiolabeled u PA was found in all melanoma cell lines . ^^^ The two u PA and PAI 1 producing cell lines showed the highest frequency to form spontaneous lung metastases after subcutaneous inoculation , whereas five of the six cell lines formed lung colonies after intravenous inoculation . ^^^ In conclusion , u PA mediated matrix degradation in vitro and production of u PA and PAI 1 by human melanoma cell lines correlated with their ability to form spontaneous lung metastasis in nude mice . ^^^ These findings suggest a role for u PA and PAI 1 in a relatively early stage of melanoma metastasis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , the authors determined the activity and antigen levels of u PA and t PA , and their inhibitors , plasminogen activator inhibitors types 1 and 2 ( PAI 1 and PAI 2 ) , in normal mucosa , adenomatous polyps , and adenocarcinomas of the human colon . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
While t PA and u PA levels were slightly lower than in adult controls , a significant decrease in PAI activity was demonstrated and no PAI 2 could be detected in fetal plasma . ^^^ In contrast with these findings , the fibrinolytic equilibrium of pregnant women exhibited a prolonged ECLT and a strong increase in both PAI activity and PAI 2 antigen levels , while only a moderate elevation in u PA and t PA levels was measured . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In 22 human tumor cell lines the regulation of production of plasminogen activators urokinase ( u PA ) and tissue type ( t PA ) and their inhibitors PAI 1 and PAI 2 was studied . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In order to investigate this question , we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin , tissue type plasminogen activator ( t PA ) , urokinase ( u PA ) , PAI 1 and PAI 2 . ^^^ Conversely , in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti PAI 1 and to a lesser extent with anti t PA antibodies . u PA and PAI 2 were not detected in these lesions . ^^^ This is in agreement with our previous findings that glomerular epithelial cells release both PAI 1 and the inactive form of u PA ( pro u PA ) . ^^^ Thus , our results support the hypothesis that PAI 1 , which is able to inhibit both t PA and u PA , may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor type 1 ( PAI 1 ) was identified in extracts of Lewis lung carcinoma , and its immunohistochemical localization was studied together with that of urokinase type ( u PA ) and tissue type ( t PA ) plasminogen activators . ^^^ Most often , areas that contained u PA immunoreactivity also contained PAI 1 immunoreactivity . ^^^ However , several areas showed a strong u PA immunoreactivity , but no or low PAI 1 immunoreactivity . ^^^ Lung metastases always contained u PA immunoreactivity , while PAI 1 immunoreactivity was found in most , but not all , metastases . t PA immunoreactivity was found in a few scattered tumor cells , in primary carcinomas as well as metastases . ^^^ Controls that included absorption with highly purified antigen preparations and immunoblotting , indicated that all the immunoreactivity represented genuine PAI 1 , u PA and t PA , respectively . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Species of PAs and PAI secreted from the GECs were urokinase type PA ( u PA ) and tissue type PA ( t PA ) , while the major species was a single chain u PA in the amount of 28 . 6 + / 2 . 34 ng / 10 ( 5 ) cells for 24 hours ( N = 4 , mean + / SD ) , and PAI 1 . ^^^ The addition of increased concentrations of thrombin ( 0 . 1 to 31 . 6 U / ml ) into confluent cultures enhanced the GECs to release u PA , t PA and PAI 1 in a dose and time dependent manner . ^^^ The incubation of the GECs with 10 U / ml thrombin resulted in about a fourfold increase in the concentration of u PA , threefold in t PA and twofold in PAI 1 . ^^^ IL 1 enhanced the release of t PA and PAI 1 , and TNF did that of u PA and t PA , while gamma IFN showed no significant effects . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Although less prominent , t PA and a 48 kDa form of u PA follow a similar pattern of induction and inhibition ; ( 2 ) changes in u PA activity in response to castration and cortisol treatment are due to alterations in the level of u PA mRNA and protein rather than in the activity of PAI 1 ; ( 3 ) not all castration induced proteinases in the prostate are inhibited by cortisol . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Upon stimulation of early passage umbilical vein endothelial cells by TNF , u PA was predominantly secreted at the basolateral side , whereas PAI activity and t PA were found in more equal amounts at the apical and basolateral sides of the cell monolayers . ^^^ The u PA antigen was present in a plasmin activatable form ( single chain u PA ) and in a nonactivatable form ( probably u PA : PAI 1 complex ) . ^^^ The parallel induction of the synthesis and secretion of both u PA and PAI 1 by endothelial cells adds a new aspect to the alterations of the fibrinolytic system caused by inflammatory mediators . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The catalytically active two chain forms of u PA , but not the inactive proenzyme single chain form , complex with PAI 1 and inhibit specific binding of 125I t PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This inhibition was correlated with an increase in PAI 1 antigen expression , whereas urinary type plasminogen activator ( u PA ) secretion was unaffected . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TPA treated K 562 cells also synthesize and secrete platelet derived growth factor ( PDGF ) , transforming growth factor beta 1 ( TGF beta 1 ) , urokinase plasminogen activator ( u PA ) and its specific inhibitor , type 1 plasminogen activator inhibitor ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The surface bound u PA was not inhibited by its physiologic inhibitors , PAI 1 or PAI 2 , whereas free u PA was . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasma concentrations of tissue type plasminogen activator ( t PA ) , urokinase ( u PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and PAI 2 were studied in 53 patients with liver deficiency caused by chronic alcoholism ( n = 40 ) , viral hepatitis ( n = 10 ) or malignant disease of the liver ( n = 3 ) and compared to that of a control group ( n = 20 ) of healthy subjects . u PA and PAI 1 levels were significantly increased in all patients with chronic alcoholism , whereas high t PA was only observed in combination with disturbed liver function tests or with liver cirrhosis ( two and six fold above control values , respectively ) . ^^^ In patients with infectious hepatitis or with malignant disease of the liver t PA was normal whereas u PA and PAI 1 were increased . ^^^ Thus , in liver disease , marked elevations of t PA , u PA and PAI 1 levels may occur , with increased PAI 1 as an early marker of liver defects and t PA a marker of severe liver defects . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , squamous cell carcinoma derived cell lines secreted plasminogen activator only after treatment with the phorbol ester 12 O tetradecanoylphorbol 13 acetate ; enhanced levels of u PA , t PA , and plasminogen activator inhibitor 1 mRNAs could then be demonstrated . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasma concentrations of urokinase plasminogen activator ( u PA / competitive radioimmunoassay ) , tissue type plasminogen activator ( t PA / sandwich ELISA ) and plasminogen activator inhibitor ( PAI / functional assay ) were determined in 44 women ( age : 24 . 3 + / 4 . 3 years ) with normal pregnancy near term . ^^^ Compared with an age matched non pregnant control group ( 8 . 3 + / 3 . 94 U / ml ) significantly increased PAI activity ( 12 . 13 + / 4 . 79 U / ml p less than 0 . 005 ) was measured before delivery with a subsequent significant decrease ( 8 . 13 + / 1 . 97 U / ml ) to normal values on day 1 after delivery ; plasma u PA and t PA antigen levels remained unchanged . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
They synthesize and secrete tissue type plasminogen activators ( t PA ) , urinary type plasminogen activators ( u PA ) , as well as plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Synthesis of t PA , u PA , and PAI 1 are regulated by a variety of external agonists . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type ( u PA ) and tissue type ( t PA ) plasminogen activators are decreased in the culture media of TGF beta treated cells concomitantly with the increase in PAI 1 accumulation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Four fibrinolytic parameters , i . e . fibrinolytic activity at rest ( FAr ) , fibrinolytic response after 10 minutes of venous occlusion ( delta FA 10 ' ) , and resting antigenic levels of the plasmatic inhibitor of the plasminogen activators ( PAI 1 ) and of urokinase ( u PA ) , showed significant differences between the two study groups . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Constitutive gene expression of four components of plasminogen activating enzyme system , urinary and tissue type plasminogen activator ( u PA and t PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and PAI 2 in HT 1080 human fibrosarcoma cells , was modulated by the synthetic glucocorticoid dexamethasone ( Dex , 10 ( 7 ) M ) . ^^^ More than 90 % of u PA , t PA and PAI 1 antigen was found in conditioned medium , whereas PAI 2 was mainly cell associated . ^^^ In 48 h culture supernatants ( expressed per 10 ( 6 ) cells ) PAI 1 antigen increased from 350 to 3 , 300 ng and t PA from 19 to 38 ng . u PA and PAI 2 in the same samples decreased from 380 to 46 ng and from 3 . 5 to 1 . 8 ng , respectively . ^^^ Northern blot hybridization and nuclear `` Run on ' ' transcription assays demonstrated that the increase of t PA and PAI 1 and the decrease of u PA were associated with equivalent changes of gene template activity . ^^^ Modulation of u PA , t PA and PAI 1 gene expression by Dex was completely blocked by the glucocorticoid antagonist RU 38486 , suggesting that all effects were mediated through the glucocorticoid receptor . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The hybrid molecules form a 1 : 1 molar complex with the human endothelial plasminogen activator inhibitor ( PAI 1 ) , analogous to that formed by rt PA and HMW u PA . ^^^ The relative affinity of rt PA for PAI 1 is 4 . 6 fold higher than that of HMW u PA . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Our knowledge about the components of the fibrinolytic system has greatly increased during the last few years thanks to the cloning of the cDNA of the two plasminogen activators t PA and u PA , of the two plasminogen activator inhibitors PAI 1 and 2 , and of other profibrinolytic and of inhibitory factors of this system . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The following tests were performed : euglobulin clot lysis time ( ECLT ) , fibrinolytic activity of euglobulins on fibrin plates in the presence and absence of blocking antibodies to tissue type plasminogen activator ( t PA ) and / or urokinase ( u PA ) , overall plasminogen activator inhibitor ( PAI ) activity , antigen levels of t PA , u PA and PAI 1 and zymography of the euglobulin fraction after SDS PAGE . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A plasminogen activator inhibitor ( PA 1 ) which inhibits primarily plasminogen activator of the urokinase type ( u PA ) was isolated from the cytosol of human peripheral leukocytes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To determine whether the other major PA , urokinase ( u PA ) , which also complexes with PAI 1 , is metabolised via the same mechanism , 125I labelled high ( hmw ) and low ( lmw ) molecular weight forms of u PA were incubated with Hep G 2 cells at 4 degrees C for 2 hr in the absence and presence of a 100 fold excess of unlabelled ligand in order to detect specific binding . ^^^ Both hmw and lmw 125I u PA formed complexes with PAI 1 and these bound specifically and with high affinity ( apparent Kd 3 . 9 and 4 . 1 nM , with Bmax 78 10 10 ( 3 ) and 83 10 10 ( 3 ) binding sites / cell respectively ) . ^^^ Binding by each form of radiolabelled u PA was inhibited in a dose dependent fashion by unlabelled t PA , hmw u PA , lmw u PA , and by monoclonal anti PAI 1 antibody . ^^^ These findings indicate that the specificity of the previously described receptor which mediates PAI 1 dependent catabolism of t PA by Hep G 2 cells extends to complexes of u PA with this inhibitor . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen , plasminogen activator inhibitor 1 ( PAI 1 ) and 2 ( PAI 2 ) , tissue type plasminogen activator ( t PA ) , urokinase ( u PA ) and D dimers ( D D ) were quantified in plasma samples and pleural effusion specimens . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The increase in PAI 1 and TF mRNA was also seen when HepG 2 were incubated with HGF in the presence of cycloheximide , thereby indicating that de novo protein synthesis is not required to mediate the effect . u PA could be detected neither in unstimulated or HGF stimulated HepG 2 cells on the antigen level nor on the mRNA level . ^^^ One could speculate that HGF might modulate processes requiring matrix degradation by increasing the expression of the protease u PA in one cell type and by upregulating the expression of the serine protease inhibitor PAI 1 in a different cell type . ^^^ Because u PA has been shown to activate latent HGF to the active form , it could furthermore be speculated that by upregulating PAI 1 , which in turn could inhibit u PA , HGF might regulate its own activation . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Suramin reduces cell associated u PA activity and greatly increases PAI 1 production at doses which induce monolayer disruption . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The low density lipoprotein receptor related protein / alpha 2 macroglobulin receptor ( LRP ) mediates endocytosis of a number of structurally unrelated ligands , including complexes of plasminogen activator inhibitor type 1 ( PAI 1 ) and tissue type plasminogen activator ( t PA ) or urokinase plasminogen activator ( u PA ) , free t PA , single chain urokinase ( pro u PA ) , alpha 2 macroglobulin protease complexes , and lipoprotein lipase . ^^^ PAI 1 complexes ( IC 50 = 1 . 1 nM ) and completely inhibits the binding of [ 125I ] pro u PA to the receptor ( IC 50 = 2 . 2 nM ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
However , at this stoichiometry , only a minority of 125I scu PA molecules formed SDS stable complexes with PAI 1 ( i . e . complexes that formed a covalent bond upon denaturation ) , even though the uncomplexed PAI 1 molecules remained competent to inhibit u PA enzymatic activity . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Although procoagulant molecules ( e . g . , tissue factor [ TF ] ) and fibrinolytic components ( e . g . , urokinase [ u PA ] and type 1 plasminogen activator inhibitor [ PAI 1 ] ) have been detected in alveolar fluid from injured lungs , the origin of these molecules remains unknown . ^^^ Injured lung tissue extracts contained elevated levels of PAI 1 activity and decreased levels of u PA activity . ^^^ In situ hybridization of injured lungs revealed that PAI 1 , u PA , and TF mRNAs were induced within the fibrin rich fibroproliferative lesions , primarily in fibroblast like and macrophagelike cells , respectively , while TF mRNA was also induced in perilesional alveolar cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
From four of the mixed primary tumors with distinct melanotic and amelanotic zones , the respective components were propagated separately in transgenic hosts as s . c . transplants to obtain data for clearly identifiable melanotic versus amelanotic parts . u PA and PAI 1 mRNAs were expressed in all . t PA expression varied greatly and was notably high in several amelanotic tumors or tumor components , possibly as a result of large blood vessels , as such vessels were seen to be t PA positive in normal tissue . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Therefore , we recently conducted a histochemical study of the distribution of t PA , Urokinase type PA ( u PA ) and PAI in transplanted kidneys . ^^^ These renal samples as well as control samples ( biopsied from normal nongrafted kidney ) were examined as to distribution of t PA , u PA and PAI by the indirect enzyme complement method . ^^^ In conclusion , t PA , u PA and PAI were detected in the glomeruli , arterioles , tubule and interstices of the control kidneys , well functioning grafts , acutely rejected grafts chronically rejected grafts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Type 1 PA inhibitor ( PAI 1 ) mRNA was expressed at the base of the necrotic atheroma of all specimens and also within some of the inflammatory infiltrates where it frequently colocalized in regions containing u PA and t PA mRNA expressing cells . ^^^ However , in these areas , the cellular distribution of the transcripts for t PA and u PA extended far beyond the areas of PAI 1 expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 ) , while there was no or very weak binding of active site blocked u PA ( DFP u PA ) , PAI 1 or u PA type 2 plasminogen activator inhibitor complex . ^^^ PAI 1 , severalfold higher than non transfected parental CHO cells . u PA . ^^^ PAI 1 endocytosis was partially inhibited by DFP u PA , which blocks binding of the complex to the u PA receptor . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Conditioned media were assayed for urokinase type and tissue type PA ( u PA and t PA , respectively ) , PA inhibitor 1 ( PAI 1 ) , and PA activity . ^^^ Binding of [ 125I ] u PA and [ 125I ] u PA : PAI 1 complex to the u PA receptor and clearance of these ligands were studied . ^^^ The PA activity of conditioned medium decreased after stimulation with progesterone , and this was secondary to a decrease in u PA , but not t PA , and an increase in PAI 1 . ^^^ Northern blot analysis showed induction of PAI 1 messenger ribonucleic acid , whereas the content of u PA messenger ribonucleic acid was not influenced . ^^^ Our data suggest that differentiated endometrial stroma in the secretory phase regulates extracellular proteolysis by increased elimination of u PA through increased release of PAI 1 and increased u PA receptor density . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrin degradation is plasmin dependent and is regulated by the balance between plasminogen activators ( PA ) , tissue PA ( t PA ) , urokinase PA ( u PA ) , and their inhibitors ( PAI ) . ^^^ Fibrin induction of t PA was selective because the levels of u PA ( 45 kD ) , PAI 1 ( 50 kD ) , or protein synthesis in general were unaffected . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of PAI 1 , t PA and u PA in cultured human umbilical vein endothelial cells derived from racial groups . ^^^ To determine whether inherent fibrinolytic differences may exist in racial groups ( black americans , BA vs . white americans , WA ) , 55 different individual racially derived human umbilical vein endothelial cell ( HUVEC ) cultures ( 35 BA and 20 WA ) were analyzed in terms of their fibrinolytic protein ( t PA , u PA and PAI 1 ) antigen and mRNA levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Methods for measuring antigen and activity of plasminogen activators ( t PA , u PA ) , plasminogen activator inhibitors ( PAI 1 , PAI 2 ) and their complex have been improved in the past few years , but few comparative data are available and they should be standardized . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase ( u PA ) is expressed in stromal cells and only in tumour cells at invasive foci , urokinase receptor ( u PAR ) in tumour cells , plasminogen activator inhibitor type 1 ( PAI 1 ) in the intratumoral extracellular matrix and plasminogen activator inhibitor type 2 ( PAI 2 ) in tumour cells and stromal cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the present study the expression of tissue type plasminogen activator ( t PA ) , urokinase plasminogen activator ( u PA ) and plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) antigen in conditioned medium from cultured human umbilical vein ( HUVEC ) and human saphenous vein ( HSVEC ) endothelial cells was investigated under basal conditions and after stimulation with LPS , TNF alpha , interferon gamma ( IFN gamma ) or interleukin 6 ( IL 6 ) alone or in combinations . ^^^ Stimulation with LPS or TNF alpha increased the expression of PAI 1 , u PA and PAI 2 in HUVEC and HSVEC , while the t PA response differed between the two cell types . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of the plasminogen activators u PA and t PA as well as the inhibitor PAI 1 were studied immunohistochemically in 35 osteosarcoma specimens compared to 15 Ewing ' s sarcomas and various other bone lesions . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
For most of the components of the PA / plasmin system , a decrease in mRNA expression and u PA receptor protein was observed at most cell densities , whereas for PAI 1 only in keratinocytes a marked increase was documented . ^^^ This occurred despite the increase u PA immunoreactivity and was probably caused by the markedly elevated levels of immunoreactive PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Single chain u PA ( scu PA ) was recently found to efficiently initiate cell surface plasminogen activation , and we herein describe the interaction of scu PA with PAI type 2 ( PAI 2 ) . ^^^ Although scu PA did not form SDS stable complexes with PAI 2 , preincubation of scu PA with 125I PAI 2 demonstrated a dose dependent inhibition of SDS stable complex formation between 125I PAI 2 and subsequently added two chain u PA . ^^^ This indicates that although a `` stable intermediate ' ' type complex between scu PA and PAI 2 was not detected , there was a physical association between the two molecules that shared at least some determinants with the two chain u PA PAI 2 complex . ^^^ In contrast , Glu 158 scu PA bound to u PA receptors on monocytes was only minimally inhibited by a large molar excess of PAI 2 . ^^^ These data suggest that the initiation of cell surface plasminogen activation may involve the partitioning of scu PA between PAI 2 ( a `` negative modulator ' ' ) and the u PA receptor ( a `` positive modulator ' ' ) and that the enzymatic activity of receptor bound scu PA may allow initiation of cell surface proteolysis even in PAI 2 rich environments . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The conversion of plasminogen into serine protease plasmin with fibrinolytic activity depends on the actual balance between plasminogen activators ( urokinase type ; u PA and tissue type ; t PA ) and their inhibitors ( type 1 and 2 plasminogen activator inhibitors ; PAI 1 and PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the same subjects we also measured plasma antigen levels of tissue type PA ( t PA ) , urokinase type PA ( u PA ) , PAI 1 , PAI 2 , and D dimer . ^^^ Plasma levels of D dimer were markedly increased in the patient ' s group ( p < 0 . 001 ) , whereas u PA and PAI 2 antigens did not differ from controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We quantitated urokinase and tissue plasminogen activator ( u PA , t PA ) , plasminogen activator inhibitor 1 and 2 ( PAI 1 , PAI 2 ) , and fibrinolytic activity in peripheral blood ( PB ) , tumour blood ( TB ) , peritoneal / ascitic fluid ( PAF ) and cystic fluid ( CF ) from 104 patients with benign and 36 patients with malignant ovarian tumours , and in peripheral blood from 62 healthy controls . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The B 16 cell lines did not secrete any gelatinase , but they secreted TIMP 2 , tissue type ( t PA ) , urokinase type ( u PA ) plasminogen activators and PAI 1 like activities . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
TNF alpha enhances urokinase plasminogen activator ( u PA ) activity and steady state mRNA levels twofold without affecting tissue plasminogen activator ( t PA ) or PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , we measured the antigen levels of urokinase ( u PA ) , tissue plasminogen activator ( t PA ) , type 1 plasminogen activator inhibitor ( PAI 1 ) , and type 2 plasminogen activator inhibitor ( PAI 2 ) , and cancer tissue ( 19 adenocarcinomas and 19 squamous cell carcinomas ) and normal lung tissue . ^^^ RESULTS . u PA , PAI 1 , and PAI 2 antigen levels in cancer tissue were significantly higher than those in normal tissue ( P < 0 . 001 in u PA and PAI 1 ; P < 0 . 005 in PAI 2 ) , whereas t PA antigen levels in cancer tissue were significantly lower than those in normal tissue ( P < 0 . 005 ) . ^^^ In case with lymph node involvement ( LN+ cases ) , PAI 2 antigen levels were significantly lower than those in cases without lymph node involvement ( LN cases ) ( P < 0 . 02 ) , whereas there was no difference in either u PA or PAI 1 antigen levels between these two groups . ^^^ The antigen levels of u PA , PAI 1 , and PAI 2 in cancer tissue were significantly higher than those in normal tissue , and lower content of PAI 2 was associated with lymph node metastasis . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Isotretinoin ( 40 mg ) was administered in the morning and in the evening for 5 days . t PA , u PA and PAI 1 antigen and activity in plasma were measured every morning at 9 a . m . on days 1 to 4 and every 3 hours over 24 hours on day 5 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Expression of plasminogen activators ( PA ) , tissue type ( t PA ) and urokinase type ( u PA ) , as well as PA inhibitors ( PAI ) , type 1 ( PAI 1 ) and type 2 ( PAI 2 ) , were investigated immunohistochemically in 97 human pancreatic carcinomas . u PA expression predominated in pancreatic carcinomas , compared with t PA [ u PA expression in 76 specimens ( 78 . 4 % ) and t PA in eight specimens ( 8 . 2 % ) ] . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recently , we reported that highly metastatic behavior of human melanoma cells in nude mice correlates with urokinase type PA ( u PA ) expression and activity and with PA inhibitor type 1 and 2 ( PAI 1 , PAI 2 ) expression . ^^^ Tissue type PA was present in endothelial cells in all lesions , whereas in metastases it could be detected in tumor cells in a minority of the lesions . u PA , its receptor , PAI 1 , and PAI 2 could not be detected in benign and in early stages but appeared frequently in advanced primary melanoma and melanoma metastasis lesions . u PA was detected in stromal cells and in tumor cells at the invasive front , the u PA receptor and PAI 2 in tumor cells , and PAI 1 in the extracellular matrix surrounding tumor cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We studied the plasminogen activation system in tumor tissue by measuring the antigen level of the 2 plasminogen activators , tissue type ( t PA ) and urokinase type ( U PA ) and their inhibitors , plasminogen activator inhibitors type 1 ( PAI 1 ) and type 2 ( PAI 2 ) in the tissue extracts of 43 human benign and malignant ovarian tumors . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Treatment of HL 60 , K 562 , THP 1 , and U 937 cells with PMA resulted in an induction of urokinase type PA ( u PA ) , the u PA receptor ( u PAR ) , and PAI types 1 and 2 ( PAI 1 and PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the absence of accessory components , plasminogen activator inhibitor 1 ( PAI 1 ) rapidly forms equimolar , inactive complexes both with tissue type ( t PA ) and with urokinase type ( u PA ) plamsinogen activator . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Concentrations of PAI 2 correlated significantly with SF leukocyte count and cytidine deaminase ( CD ) activity and u PA concentrations correlated with CD activity . ^^^ Both PAI 2 and u PA were detected in supernatants from lysed polymorphonuclear cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Venous blood samples were taken at time 0 , 3 , 6 , 25 and 49 h for assay of fibrinogen ( Fbg ) , fibrinopeptide A ( FPA ) , total fibrin ( ogen ) degradation products ( TDP ) , fibrin degradation products ( FbDP ) , fibrinogen degradation products ( FgDP ) , cross linked fibrin degradation products ( XL FDP ) , tissue plasminogen activator ( tPA ) , urinary type plasminogen activator ( u PA ) , plasminogen , alpha 2 antiplasmin ( alpha 2 AP ) and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator activity ( PAA ) and plasminogen activator inhibition ( PAI ) , against t PA ( t PAI ) or u PA ( u PAI ) , in spermatozoa and seminal plasma as well as testosterone in the blood of Friesland , Chios , and Karagouniki rams all showed a seasonal variation with the highest values during the corresponding breeding season of the ewes ( Autumn Winter ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Lysis of blood clots from vehicle and retinoic acid treated rats could be completely blocked by addition of tranexamic acid or antibodies against rat t PA before clot formation . t PA activity in plasma was slightly increased after retinoic acid treatment ; no effects were measured on plasma PAI 1 , u PA , plasminogen , and alpha 2 antiplasmin levels . t PA activity in lung and kidney was marginally enhanced by retinoic acid but in heart and aortic tissue extracts t PA activity was increased by about 50 % . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These findings were also reflected in the specific mRNA levels as determined by Northern blotting . u PA specific mRNA increased significantly in HFMEC in the presence of IL 4 , whereas t PA mRNA and PAI 1 specific mRNA in HFMEC and u PA specific mRNA in human saphenous vein EC ( HSVEC ) remained unaffected by IL 4 treatment . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We , therefore , performed immunohistological studies on human colon tumours using monoclonal antibodies against urokinase ( u PA ) and tissue type plasminogen activator ( t PA ) as well as against plasminogen activator inhibitors 1 and 2 ( PAI 1 , PAI 2 ) . ^^^ However , two of four human colon carcinoma cell lines weakly expressed u PA , PAI 1 and PAI 2 . ^^^ Intestinal dendritic or fibroblast like cells within the tumour tissue strongly expressed u PA and , at a lower level , also t PA , PAI 1 and PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The urokinase plasminogen activator ( u PA ) and its inhibitor ( PAI 1 ) in embryo fetal bone formation in the human : an immunohistochemical study . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The balance of proteases and inhibitors differed dramatically from that observed in plasma , with higher levels of t PA , PAI 1 and PAI 2 , and lower levels of u PA ( urokinase ) , plasminogen , alpha 2 AP and t PA PAI 1 complex in bone marrow , and resulted in favourable conditions for fibrinolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Similarly , VN binding to purified ( immobilized ) u PA receptor , but not to integrin , was enhanced by u PA and inhibited by PAI 1 . ^^^ Hence , the binding of soluble VN to endothelial cell surfaces is mediated by the u PA receptor , and the relative concentrations of u PA and PAI 1 are able to regulate the strength of this interaction . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The expression of tissue type plasminogen activator ( t PA ) , urokinase type PA ( u PA ) and PA inhibitor 1 ( PAI 1 ) in such treated cells was investigated by specific ELISAs on the protein level and by Northern blotting on the mRNA level . ^^^ AZA caused a time and dose dependent decrease in the fibrinolytic potential of all three cell lines investigated by decreasing t PA antigen in Bowes , by decreasing u PA antigen in GUBSB and by increasing PAI 1 antigen in MJZJ cells , respectively . ^^^ The effect of AZA on specific mRNA for t PA in Bowes cells , u PA in GUBSB and PAI 1 in MJZJ was consistent with its effect on the secretion of these fibrinolytic proteins by the respective cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We investigated the effects of IL 1 on the production of tissue type plasminogen activator ( t PA ) , urokinase ( u PA ) and PAI 1 by glomerular cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The binding of u PA and PAI 1 to the u PA receptor may cause internalization of the trimeric complex into the cell and activate a tyrosine kinase . ^^^ In a prospective study the u PA , u PA R , and PAI 1 content in patients with renal cell carcinoma ( RCC ) and benign renal tissue were correlated with traditional prognostic factors such as the TNM staging , histologic grading , ploidy , and the clinical outcome of the patients . ^^^ METHODS : One hundred fifty two patients who underwent transperitoneal tumor nephrectomy for RCC were followed up for a mean of 23 . 9 months . u PA , u PA R , and PAI 1 from the tumor tissue and corresponding benign renal tissue were quantified from detergent extracted tissue samples ( 1 % Trinton 10 100 in triethanolamine buffered saline ) and measured with an enzyme linked immunoadsorbent assay . ^^^ CONCLUSIONS : u PA , u PA R , and PAI 1 are strong and independent prognostic factors for predicting early relapse for RCC . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The endothelial cells which had not been treated with LPS produced and secreted a large amount of urokinase type PA ( u PA ) , and small amounts of tissue type PA ( t PA ) and PA inhibitor 1 ( PAI 1 ) , which were identified immunohistochemically and by electrophoretic enzymography . ^^^ These findings suggest that the established endothelial cell line , TKM 33 , possesses the characteristics of endothelial cells and they express u PAR on their cell surface , which is occupied by intrinsic u PA secreted from the cells , and that treatment of endothelial cells with LPS changes the cell surface characteristics and inhibited the u PAR expression thus promoting the prothrombotic function concomitantly with increased PAI 1 activity . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Conflicting results have been obtained concerning the production of urokinase type PA ( u PA ) and efforts to show PA inhibitor 2 ( PAI 2 ) met with failure . ^^^ Subconfluent cells ( third passage ) were incubated overnight in serum free medium . t PA , u PA , PAI 1 and PAI 2 antigens were assayed by ELISA methods and PA and PAI activities by amidolytic methods both in conditioned medium ( CM ) and cell extracts ( CE ) . ^^^ At variance with the former , which was largely released in the culture medium , PAI 2 was mainly cell associated . t PA antigen was found in all but two cell lines while u PA antigen was detected in relatively high concentrations in 8 cell lines . ^^^ PA activity , identified as u PA by functional and immunological criteria , was measured in CM of six of the eight u PA producing cell lines , whereas PAI activity was undetectable or very low in CM of all cell lines , suggesting that PAI 1 was largely inactive . ^^^ Functional assays of cell extracts demonstrated the presence of PA activity , again identified as u PA , only in samples ( five lines ) containing u PA antigen in excess over PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Direct and reverse fibrin zymography indicated the presence of urokinase like plasminogen activator ( u PA ) and PAI 1 in U 251 conditioned media and cell lysates . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Since PAI 1 inhibits the 2 major plasminogen activators , tissue type plasminogen activator ( t PA ) and urinary type plasminogen activator ( u PA ) in an equimolar manner it was important to establish the potency of the PAI 1 inhibitor in terms of both t PA and u PA neutralisation . ^^^ Belgium in September 1994 ) has recommended that the plasma PAI 1 ( 92 / 654 ) should be accepted as the International Standard for PAI 1 and should define a unitage in terms of both t PA and u PA neutralisation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
EGF also stimulated the release of urokinase type PA ( u PA ) , as well as the release of PA inhibitor type 1 ( PAI 1 ) . ^^^ These stimulatory effects on the release of t PA and PAI 1 , but not of u PA , were enhanced by the concomitant addition of progesterone . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PATIENTS AND METHODS : In 50 consecutive node positive breast cancer patients , serial coagulation studies ( fibrinogen method of Clauss , antithrombin 3 , protein C amidolytic methods , D dimer enzyme linked immunoadsorbent assay [ ELISA ] techniques , and plasminogen activator inhibitor [ PAI ] activity u PA inhibition test ) and impedance plethysmography ( IPG ) for screening of deep vein thrombosis ( DVT ) were performed preoperatively and postoperatively , before each of six cycles of adjuvant chemotherapy ( 60 mg / m2 epirubicin and 600 mg / m2 cyclophosphamide ) and 3 months thereafter . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The endothelial cells produced and secreted large amounts of u PA and low levels of tissue type PA ( t PA ) and of PA inhibitor 1 ( PAI 1 ) , which were identified by immunohistochemical study and electrophoretic enzymography . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We aimed to investigate TGF beta 1 , u PA and PAI 1 gene expressions in relation to proliferation and extracellular matrix ( ECM ) protein gene expressions in porcine arteries following injury . ^^^ RESULTS : TGF beta 1 , u PA and PAI 1 transcripts were rapidly elevated ( 2 8h ) and preceded a peak in histone mRNA at 24h after arterial injury . ^^^ CONCLUSIONS : The timings of increases in TGF beta 1 , u PA and PAI 1 mRNAs in injured arteries are consistent with contributions to processes prior to proliferation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Evidence has been presented that primary breast cancer patients with tumors containing high levels of u PA experience a worse prognosis . u PA and its inhibitor , type 1 plasminogen activator inhibitor ( PAI 1 ) , are potentially important prognostic factors in breast cancer to identify patients at high risk for recurrence and also in the classification of clinically important subgroups . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , u PA , t PA and PA activator 1 ( PAI 1 ) antigen and activity were measured in plasma and pleural fluid samples from patients with MPM , lung cancer and benign effusion . ^^^ These findings were in contrast to the lung cancer group , in which both activity and immunologic measurement of u PA and t PA were higher , but PAI 1 antigen was similar as compared to the control group . ^^^ It is concluded that excess t PA and u PA are balanced in complexes with PAI 1 in MPM , whereas the amount of PAI 1 in plasma is insufficient to overcome the elevated t PA and u PA , in lung cancer . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Localization of t PA , u PA , PAI 1 , PI and TGF beta within tumors was examined immunohistologically in 31 patients with squamous cell carcinoma ( SCC ) of the head and neck , and correlations between the localization of these factors and local cancer infiltration , tumor size or cervical lymph node metastasis were investigated . ^^^ The results revealed that u PA , PAI 1 and PI tend to stain more intensely in infiltrating tumors than in peripheral connective tissue or normal epithelium , whereas neither t PA nor TGF beta showed any such tendency . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Murine recombinant two chain u PA bound to murine endothelioma cells was quantitatively inhibited by murine plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^ Thus , the interactions between murine plasminogen , u PA and PAI 1 are qualitatively similar to those between their human counterparts . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
These results suggest that BFA can strengthen the defense of vascular endothelium against tumor cell invasion by enhancing the release and accumulation of PAI 1 , which plays a critical role in the regulation of the u PA plasmin collagenase activation cascade . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this study , the expression of three glycoproteins that play a role in the plasminogen activator system as activators of proteolysis urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) were studied in various components of dedifferentiated chondrosarcomas of bone . ^^^ METHODS : The expression of u PA , t PA , and PAI 1 was investigated in 10 dedifferentiated chondrosarcomas and 14 conventional chondrosarcomas . ^^^ RESULTS : In dedifferentiated chondrosarcoma , high grade dedifferentiated components displayed strong , diffuse coexpression of u PA , t PA , and PAI 1 . ^^^ In the latter , u PA , t PA , and PAI 1 expression was found to be enhanced at invasive foci and in regions of endochondral ossification . ^^^ CONCLUSIONS : The current study documents the overexpression of u PA , t PA , and PAI 1 in dedifferentiated chondrosarcoma and suggests involvement of the plasminogen activator system in the biology of these tumors . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Incubation with transforming growth factor beta 1 resulted in a decrease in plasminogen activation , primarily because of an increase in plasminogen activator inhibitor 1 RNA and protein and a decrease in u PA RNA as noted by quantitative reverse transcriptase polymerase chain reaction , Western analysis , and zymography . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This PAI 1 was partly co localized with macrophages , as was the urokinase plasminogen activator ( u PA ) , suggesting an involvement of these cells in peritoneal tissue fibrinolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Progressively aggressive neoplastic cells evidence high expression of u PA and u PAR activities , variable expression of t PA , and enhanced PAI 1 and PAI 2 activities . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Inactivated samples of porcine PAI 1 could be reactivated with guanidinium chloride up to 52 % of its original specific activity towards t PA and u PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In previous studies we found that colorectal carcinomas have a marked increase of the urokinase type of plasminogen activator ( u PA ) , and the inhibitors PAI 1 and PAI 2 , whereas the tissue type plasminogen activator ( t PA ) is found to be decreased in comparison with adjacent normal mucosa . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
On Northern blot analysis of mRNA obtained from NG R 1 stimulated and control HPASMCs NG R 1 induced a significant increases in mRNA levels of t PA and u PA ( 180 % and 200 % of control value , respectively ) at 100 micrograms NG R1 / ml while PAI 1 mRNA decreased slightly . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Quantitative reverse transcription polymerase chain reaction and in situ hybridization were employed to investigate the expression of tissue type and urokinase type plasminogen activators ( t PA and u PA , respectively ) , of their specific inhibitor ( PAI 1 ) , and of the procoagulant molecule tissue factor ( TF ) in tissues from mice that develop autoimmune disease ( MRL lpr / lpr ) . ^^^ In addition to these changes in PAI 1 , decreases in u PA mRNA and increases in TF mRNA were demonstrated in kidneys from the lupus prone mice . ^^^ The increase in PAI 1 and TF mRNAs and the decrease in u PA mRNA in the kidneys of MRL lpr / lpr mice suggests that changes in the expression of these genes may promote the formation of microthrombi and thus contribute to the progression of lupus nephritis in this model . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tissue and urokinase plasminogen activators ( t PA , u PA ) and their inhibitor PAI 1 in blood of patients with laryngeal neoplasms ] . ^^^ In this study we measured the concentrations of tissue plasminogen activator ( t PA ) , urokinase plasminogen activator ( u PA ) , activity of plasminogen activator inhibitor type 1 ( PAI 1 ) and euglobulin lysis time ( ELT ) in the blood of 20 men aged 42 75 years old with planoepitheliale larynx carcinoma , and 10 healthy persons in similar age . ^^^ In this study the mean values of t PA , u PA concentrations , PAI 1 activity and ELT in the blood of patients with larynx carcinoma were similar to the examination results of healthy persons , but 40 % of our cancer patients have increased activity of PAI 1 . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both the xenograft and the patient ' s tumour showed intense staining for mutant p 53 nuclear protein , and high expression of U PA , PAI and u PAR . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the acute phase , intense plasminogen activator inhibitor 1 ( PAI 1 ) gene expression was apparent in areas interfacing the dissecting hematoma , but no tissue type PA ( t PA ) , urokinase type PA ( u PA ) , or MMP 9 mRNAs were detected . ^^^ Although PAI 1 mRNA was still present in the subacute phase , t PA , u PA , and MMP 9 mRNAs were now obvious , with PA gene expression co localizing with areas of PAI 1 gene expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recent studies demonstrated that u PA , plasminogen activator inhibitor type 1 ( PAI 1 ) , and tissue type plasminogen activator ( t PA ) are prognostic factors in breast cancer . ^^^ The median follow up was 52 . 6 months . u PA , PAI 1 , and t PA antigen levels were assayed by ELISA kits using the cytosolic fractions of tumors . ^^^ Patients with high u PA , high PAI 1 , or low t PA had significantly higher relapse rates than did those with low u PA , low PAI 1 , or high t PA , respectively , by the Kaplan Meier method ( P = 0 . 006 , 0 . 032 , and 0 . 028 , respectively ) . ^^^ Analyses of the combinations of both u PA and PAI 1 or both u PA and t PA showed that the differences in relapse rate between the high and low risk groups were statistically very significant . ^^^ In the univariate analysis , u PA , PAI 1 , t PA , progesterone receptor , and tumor size ( T 3 versus T 1 ) were significantly correlated with relapse . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MEASUREMENT AND RESULT : t PA , PAI 1 , t PA PAI 1 complexes , plasminogen , fibrinogen and plasmin alpha 2 antiplasmin complexes were measured serially by ELISA and free u PA by SDS PAGE with zymography . ^^^ CONCLUSION : Despite the sustained presence of active u PA in the circulation and of t PA antigen at the onset of symptoms , plasmin alpha 2 antiplasmin generation was largely suppressed by high levels of PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We applied monoclonal antibodies against MMP 1 , 2 , 3 , 9 and their inhibitors TIMP 1 / 2 , as well as against urokinase plasminogen activator u PA and its inhibitor PAI to investigate their influence on articular cartilage degradation in patients with varusgonarthritis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Increased expression of PAI 1 may play a role in inhibiting proteolysis and fostering the localization of the acute fibrin platelet thrombus to the vascular wall , which is followed by the upregulation of u PA in migrating cells during the reorganization process . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
IL 1 ( 2 ng / mL ) specifically increased the accumulation of PAI 1 ( 4 . 4 + / 0 . 6 fold ; mean + / SD ; n = 9 ) without affecting tissue plasminogen activator ( t PA ) or urokinase plasminogen activator ( u PA ) levels , which remained unchanged . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Cell motility is significantly reduced by inhibitors of u PA proteolytic activity such as antibodies neutralizing u PA activity , plasminogen activator inhibitor 1 , and amiloride . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of the specific activators ( u PA and t PA ) and the specific inhibitors ( PAI 1 and PAI 2 ) of the fibrinolytic system were analyzed in the peritoneal fluid in women suffering from intra abdominal adhesions , endometriosis or pelvic inflammatory diseases ( PID ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To investigate this question , we overexpressed plasminogen activator inhibitor 1 ( PAI 1 ) , an inhibitor of t PA and u PA , in a rat model of aortic aneurysm . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Abnormal expression of fibrinolytic genes [ e . g . , tissue type and urokinase type plasminogen activators ( t PA and u PA ) and their specific inhibitor ( PAI 1 ) ] and of the procoagulant molecule tissue factor ( TF ) , has been reported in various types of renal diseases . ^^^ In addition to these changes in PAI 1 , decreases in u PA mRNA and increases in TF mRNA were demonstrated in the kidneys from lupus prone mice as a function of age . ^^^ The induction of PAI 1 and TF , and the decrease in u PA expression in the kidneys of lupus prone or of endotoxemic mice may promote the formation of renal microthrombi and thus contribute to the progression of renal damage in these models . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The following haemostatic parameters were determined ; thrombelastography , fibrinogen , antithrombin 3 ( ATIII ) , thrombin antithrombin ( TAT ) complex , beta thromboglobulin ( beta TG ) , plasminogen activators ( t PA , u PA ) , plasminogen activator inhibitors ( PAI 1 , PAI 2 ) , and plasminogen . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Synoviocytes from osteoarthritis and rheumatoid arthritis produce plasminogen activators and plasminogen activator inhibitor 1 and display u PA receptors on their surface . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PAI 1 ovalbumin , PAI 1 antithrombin 3 and PAI 1 P 13 ( Val > Glu ) revealed specific activities of 86+ / 15 % , 77+ / 11 % , and 100+ / 30 % respectively , towards t PA and similar inhibitory properties towards u PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Endothelial cells express fibrinolytic proteins including : urokinase ( u PA ) and tissue type ( t PA ) plasminogen activators , type 1 ( PAI 1 ) and 2 ( PAI 2 ) plasminogen activator inhibitors , and u PA receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
RESULT ( S ) : The concentrations of urokinase plasminogen activator ( u PA ) and PAI 1 were higher in endometrium from women with endometriosis than in endometrium from controls and even higher in endometriotic tissue than in endometrium from both groups . ^^^ CONCLUSION ( S ) : The high concentrations of u PA and PAI 1 in endometrium from women with endometriosis might facilitate implantation of endometrial cells and the high concentration in endometriotic tissue might contribute to their invasive growth . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
During preeclampsia t PA and PAI 1 levels are markedly increased in plasma , and in cases of intrauterine growth retardation , u PA and PAI 2 levels are decreased . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We have shown that HSC produce u PAR , u PA , and PAI 1 . ^^^ PDGF and b FGF up regulate u PA and u PAR , but not PAI 1 , and exogenous addition of u PA stimulates HSC proliferation , chemotaxis , and chemoinvasion . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Therefore , we propose a role for HGF / SF in wound repair in the skin : HGF / SF produced by activated fibroblasts increases in keratinocytes the expression of PAI 1 , which leads to increased matrix stability during the repair process and which could also limit activation of HGF / SF by proteases such as urokinase type PA ( u PA ) or tissue type PA ( t PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
A cell line , TKM 33 , has been established and cloned from human umbilical vein endothelial cells , was previously reported to produce a large amount of urokinase type PA ( u PA ) and small amounts of tissue type plasminogen activator ( t PA ) and PA inhibitor 1 ( PAI 1 ) . ^^^ In the present study , we investigated the localization of u PA , t PA , PAI 1 and u PAR in TKM 33 by using immunofluorescence staining technique . ^^^ The endothelial cells were strongly stained with anti PAI 1 , anti u PA and anti u PAR IgGs , and slightly with anti t PA IgG . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The u PA system consists of plasmin , u PA , specific u PA receptor and the serpins , PAI 1 and PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Endothelial cell fibrinolysis : transcriptional regulation of fibrinolytic protein gene expression ( t PA , u PA , and PAI 1 ) by low alcohol . ^^^ Endothelial cells ( ECs ) synthesize fibrinolytic proteins , t PA , u PA , and PAs inhibitor , PAI 1 . ^^^ Further nuclear transcription run on assays and transient transfection experiments , using pPAs / luc and pPAI 1 / luc promoter constructs , demonstrated that low ethanol transcriptionally upregulates t PA and u PA gene expression and downregulates PAI 1 gene expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
To determine the ability of radiation to modulate mesangial cell expression of various molecules involved in promoting extracellular matrix ( ECM ) accumulation [ fibronectin , plasminogen activator inhibitor 1 ( Pai 1 ) , and tissue inhibitor of metalloproteinase 2 ( Timp 2 ) ] and degradation ( Tgfb , plasminogen activators u PA or t PA , matrix metalloproteinases Mmp 2 and Mmp 9 ) , primary cultures of rat mesangial cells ( passage number 6 11 ) were placed in serum free medium 24 h prior to irradiation with single doses of 0 . 5 20 Gy ( 137 ) Cs gamma rays . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Recombinant adenoviral vectors expressing u PA , t PA , PAI 1 and PAI 2 were employed to correlate the expression of components of the fibrinolytic system with the invasiveness of HT 1080 tumor cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The following parameters were determined : plasminogen activators ( t PA , u PA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , D dimer , beta thromboglobulin ( beta TG ) , thrombin antithrombin ( TAT ) complex , fibrinogen , Factor 7 , platelets , haematocrit and haemoglobin levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The plasminogen activator inhibitors 1 ( PAI 1 ) and 2 ( PAI 2 ) are two specific inhibitors of u PA . ^^^ Using immunohistochemistry , we analyzed the pattern of expression of u PA , PAI 1 , and PAI 2 in non small cell lung carcinomas ( NSCLC ) and neuroendocrine ( NE ) lung tumors . u PA and PAI 1 were both detected in stromal fibroblasts and in tumor cells . ^^^ In 72 NE tumors , u PA and PAI 1 were more frequently expressed in fibroblasts in high grade NE tumors ( SCLC and large cell NE tumors ) than in low and intermediate grade tumors ( typical and atypical carcinoids ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The present morphological study was therefore designed to investigate the occurrence and distribution of the tissue and urokinase plasminogen activators ( t PA and u PA ) , the u PA receptor ( u PAR ) and the plasminogen activator inhibitors ( PAI 1 and PAI 2 ) in normal human testis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( u PA ) and its fast acting type 1 inhibitor ( PAI 1 ) localize to cellular focal adhesive structures and the adjoining proximal undersurface region , respectively ( Kutz et al . , J . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Whereas wild type PAI 1 ( wtPAI 1 ) exhibits inhibitory properties towards t PA and u PA to an extent of 60 80 % of the theoretical maximum , PAI 1 delhF did not exert any detectable inhibitory properties , but behaved as a stable substrate . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen , plasminogen activator inhibitor ( PAI ) 1 , tissue type plasminogen activator ( t PA ) and urokinase plasminogen activator ( u PA ) were investigated in the pre surgical period and in the postoperative follow up period in children suffering from Ewing sarcoma ( ES ; n = 36 ) or osteosarcoma ( OS ; n = 39 ) . ^^^ Besides a short lasting increase of PAI 1 in patients with OS on day 1 and in children with Es on day 14 , a small and significant but clinically irrelevant difference was found on days 7 10 for plasminogen , t PA and u PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activators u PA ( urokinase ) and t PA ( tissue ) as well as the inhibitors PAI 1 and PAI 2 are present in gingival crevicular fluid in concentrations significantly greater than in plasma . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Similarly , the u PA receptor as well as the inhibitor PAI 1 were present at lower levels in BCCs relative to both SCCs and melanomas . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of tissue plasminogen activator ( t PA ) , urokinase plasminogen activator ( u PA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) in cell conditioned medium were determined by ELISA and the level of PAI 1 mRNA was determined using northern hybridisation . ^^^ RESULTS : Under basal conditions ( 5 mM glucose ) , HREC produced PAI 1 , t PA , and trace amounts of u PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : To determine the ability of radiation to modulate kidney tubule epithelial cell expression of various molecules involved in regulating extracellular matrix accumulation ( collagen types 1 and 3 , fibronectin , plasminogen activator inhibitor 1 ( PAI 1 ) , TGF beta and tissue inhibitor of metalloproteinases 2 ( TIMP 2 ) ) and degradation ( plasminogen activators u PA or t PA , MMP 2 and MMP 9 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Activity of plasminogen activator inhibitor ( PAI 1 ) , platelet adhesion and aggregation , antigens of tissue and urokinase plasminogen activators ( respectively , t PA Ag and u PA Ag ) , euglobulin lysis time ( ELT ) , complexes of plasmin antiplasmin ( PAP ) and fibrin degradation products ( FDP ) were tested before and after fourteen days administration of 20 30 mg / d prednisone . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In contrast , thrombi in wt mice , t PA ( / ) and u PA ( / ) mice were comparable , substantiating efficient inhibition of fibrinolysis by the combined PAI 1 / alpha ( 2 ) AP action . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrinopeptide A ( FP A ) , D Dimer , plasminogen activators ( PA ) of the urokinase ( u PA ) or tissue type ( t PA ) , PA inhibitor 1 ( PAI 1 ) and alpha 2 antiplasmin ( alpha 2 AP ) were determined by ELISA technique . ^^^ U PA , but not t PA levels were significantly reduced in all ILD groups . alpha 2 AP was markedly elevated throughout , whereas PAI 1 levels were lowered . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of u PA , t PA , PAI 1 and PAI 2 antigen as well as functional u PA were assessed in tissue homogenates from 20 chronic venous ulcers , six actively healing venous ulcers and five traumatic wounds . ^^^ The concentrations of functional u PA , u PA antigen and PAI 1 were significantly greater and PAI 2 was significantly lower in the edge and base of chronic venous ulcers compared to adjacent intact skin ( P < 0 . 01 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVE : Firstly , to study the effect of tea and tea polyphenols on cardiovascular risk indicators of the inflammatory system ( IL 6 , IL1beta and TNF alpha , CRP ) , and on haemostasis and endothelial proteins with an acute phase behaviour ( fibrinogen , vWF , PAI 1 , FVIIa and u PA ) . ^^^ MEASURES : Plasma levels of the inflammatory markers IL 6 , IL1beta , TNF alpha , CRP , fibrinogen , vWF , PAI 1 , FVIIa and u PA and of the antioxidants alpha tocopherol , beta carotene and vitamin C . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In these subjects , the following parameters were established : euglobulin lysis time ( ELT ) , the concentration of tissue plasminogen activator antigen ( t PA Ag ) , the concentration of urokinase plasminogen activator antigen ( u PA Ag ) , the activity of plasminogen activator inhibitor type 1 ( PAI 1 ) , the concentration of plasmin antiplasmin complex ( PAP ) and fibrinogen / fibrin degradation products ( FDP ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activators ( t PA and u PA ) and plasminogen activators inhibitors ( PAI 1 and PAI 2 ) in some myeloproliferative syndromes . ^^^ In the study we aimed to evaluate fibrinolysis system in blood plasma of the patients with selected myeloproliferative syndromes on the basis of examinations of plasminogen activators ( tissue t PA and urokinase type u PA ) and type 1 and type 2 plasminogen activator inhibitors ( PAI 1 and PAI 2 ) . ^^^ In citrate venous blood , the following parameters were determined : concentrations of antigen t PA , u PA , PAI 1 , PAI 2 , concentration of plasmin alpha 2 antiplasmin complexes ( PAP ) determined with the use of ELISA technique , PAI 1 activity with amidolytic method , euglobulin lysis time ( ELT ) according to Kowarzyk Buluk and fibrinogen / fibrin degradation products ( FDP ) concentration with the use of Merskey ' s method . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In order to determine a correlation of cell cycle phases with the fibrinolytic system , we investigated the expression of u PA , tissue type plasminogen activator ( t PA ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) in normal and tumor containing prostate extracts and analyzed a possible relationship with flow cytometry determined proliferative activity of the samples . ^^^ Methods : Samples were obtained from patients undergoing radical prostatectomy for prostate cancer and separated into two portions for DNA analysis and the detection of u PA , t PA , and PAI 1 . ^^^ The concentrations of u PA , t PA , and PAI 1 were determined from tissue extracts after homogenization by an enzyme linked immunosorbent assay ( ELISA ) technique . ^^^ Furthermore , no significant correlation of u PA , t PA , and PAI 1 with cell cycles in organ confined ( < pT3a ) and disseminated ( > or = pT3a ) tumors was found . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
All the tumours expressed matrix metalloproteinases ( MMP ) 2 and 9 , tissue inhibitor of metalloproteases ( TIMP ) 2 , urokinase plasminogen activator ( u PA ) , plasminogen activator inhibitor ( PAI ) 1 and PAI 2 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activators ( tissue type ; t PA and urokinase type ; u PA ) and plasminogen activator inhibitors ( PAI 1 , PAI 2 ) are found in high concentrations in gingival crevicular fluid ( GCF ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase plasminogen activator receptors ( u PAR ) , u PA and plasminogen activator inhibitor type 1 ( PAI 1 ) were determined by immunoassay and RNase protection assay . ^^^ TGF beta 1 up regulates the synthesis and expression of PAI 1 , as well as u PAR expression and exposure at the cell membrane , while it does not affect u PA levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary inhibitor of both tissue and urokinase type plasminogen activators ( t PA , u PA ) . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) is the primary inhibitor of both tissue and urokinase type plasminogen activators ( t PA , u PA ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Concentration of : tissue plasminogen activator antigen ( t PA : Ag ) , urokinase plasminogen activator antigen ( u PA : Ag ) , plasminogen activator inhibitor type 1 antigen ( PAI 1 : Ag ) ( ELISA ) , PAI 1 activity ( PAI 1 act . ) , euglobulin lysis time ( ELT ) ( Kowarzyk Buluk method ) , fibrinogen , fibrin degradation products ( FDP ) ( Merskey method ) in blood plasma were evaluated . ^^^ The results shows statistically higher concentrations of : t PA : Ag , PAI 1 : Ag , fibrinogen , and lower concentrations of u PA : Ag and elongated ELT in blood plasma patients with AO and DM in compare with healthy volunteers . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) inhibits plasminogen activators ( u PA and t PA ) by forming stable complexes endocytosed via a low density lipoprotein receptor superfamily member dependent mechanism . ^^^ Plasminogen activator inhibitor 1 ( PAI 1 ) inhibits plasminogen activators ( u PA and t PA ) by forming stable complexes endocytosed via a low density lipoprotein receptor superfamily member dependent mechanism . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The hypertrophy observed in this model is , however , not related to changes in fibrinolytic parameters , as suggested by our finding that levels of t PA , u PA and PAI 1 antigen as well as t PA and u PA activity were not different in SC or GON adipose tissue extracts of both genotypes . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Studies on the plasminogen activating system in gingival crevicular fluid ( GCF ) as well as gingival tissue are reviewed . t PA , u PA , PAI 1 and PAI 2 have all been detected in GCF . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Covalent complexes of these derivatized PAI 1 species were made with the proteinases trypsin , LMW u PA , HMW u PA , and t PA . ^^^ Structural similarity of the covalent complexes formed between the serpin plasminogen activator inhibitor 1 and the arginine specific proteinases trypsin , LMW u PA , HMW u PA , and t PA : use of site specific fluorescent probes of local environment . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Swapping the 37 loop of TSV PA for either that of t PA or that of u PA also increased dramatically the rate of inactivation by PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Enzyme linked immunosorbent assays ( ELISAs ) were used to measure cysteine cathepsin B ( CatB ) and cathepsin L ( CatL ) and their inhibitors , stefin A ( StA ) and stefin B ( StB ) , together with urokinase ( u PA ) and plasminogen activator inhibitor 1 ( PAI 1 ) , in 150 cytosols of primary invasive breast carcinoma . ^^^ A good correlation was found between the levels of the two cysteine proteinases but only a moderate one between those of the cysteine and serine proteinases . u PA and PAI 1 levels correlated positively with histological grade and negatively with estrogen receptor ( ER ) status . ^^^ In the total group of patients , high u PA and PAI 1 and low StB levels correlated significantly with shorter disease free survival ( DFS ) , while CatB , CatL and StA did not . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In addition , MABUC was noted to be 1 . 5 2 fold more effective in the dissolution of surfactant embedding clots and to be approximately 3 fold more resistant against PAI 1 , the predominant fibrinolysis inhibitor in the alveolar compartment , as compared to the native u PA . ^^^ We conclude that urokinase and 8B5E can be cross linked chemically , thus yielding a fibrinolytic enzyme with enhanced substrate specifity for surfactant containing clots and higher PAI 1 resistance as compared to native u PA . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
PURPOSE : The serine proteases tissue plasminogen activator ( t PA ) and urokinase plasminogen activator ( u PA ) and their inhibitor , plasminogen activator inhibitor ( PAI ) 1 , regulate a variety of processes involved in tissue morphogenesis and differentiation . ^^^ The authors investigated whether expression of t PA , u PA , and PAI 1 in human retinal glial cells ( HRGCs ) is influenced by exposure to transforming growth factor ( TGF ) beta , a cytokine that regulates the proliferation and differentiation of cells . ^^^ METHODS : The extracellular release of t PA , u PA , and PAI 1 was measured by enzyme linked immunosorbent assay ( ELISA ) in the supernatant of HRGC cultures , under basal conditions and after stimulation with TGF beta at various concentrations ( 2 , 5 , 10 , or 20 ng / mL ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The concentrations of t PA , u PA , PAI 1 and PAI 2 were measured by ELISA . ^^^ Mean concentrations of t PA , u PA , PAI 1 were lower in Group 2 ( 5 . 69 ng / ml vs 15 . 7 ; 0 . 46 ng / ml vs 0 . 7 ; 16 . 82 ng / ml vs 26 . 16 ng / ml ) or nearly equal for PAI 2 ( 343 . 53 ng / ml vs 341 . 02 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The reduced inhibitory activity of PAI 1 against t PA but not u PA suggested that the mechanism of loop insertion is sensitive to the intramolecular interactions of one or more tryptophan residues . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Overexpression of plasminogen activator inhibitor 1 ( PAI 1 ) reduces tumor cell migration in vitro and metastasis in mice in vivo by mechanisms involving either inhibition of urokinase plasminogen activator ( u PA ) activity or competition for an integrin binding site on vitronectin . ^^^ This indicates that both u PA inhibition and PAI 1 ECM interactions contribute to the mechanism of PAI 1 mediated regulation of cell migration . . ^^^ Both u PA inhibition and vitronectin binding by plasminogen activator inhibitor 1 regulate HT 1080 fibrosarcoma cell metastasis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Urokinase type PA ( u PA ) and PA inhibitor type 1 ( PAI 1 ) seem to modulate cardiac rupture and infarct healing . ^^^ We could demonstrate that HACM , isolated from pieces of myocardial tissue by mechanical dispersion and characterized by positive immunostaining for the cardiac markers troponin 1 , tropomyosin , cardiotin and myocardial muscle actin , in vitro express PAI 1 and tissue type PA ( t PA ) whereas u PA was not detectable in these cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
They could contribute to the inhibition of both cell proliferation ( down regulation of cyclin D 1 , PCNA , c myc and up regulation p 21 ( Waf 1 ) , p 19 ( INK4d ) , integrin beta 8 ) and cell invasion , either directly ( decrease in u PA , MMP 9 , u PAR , PAI 1 and increase in anti oncogenes Wnt 5a and H cadherin ) or indirectly by stimulating an anti angiogenic gene ( thrombospondin 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
SPUC was 2 3 fold more effective in lysis of surfactant containing clots and 5 fold more resistant against plasminogen activator 1 ( PAI 1 ) as compared to the native u PA . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
MATERIALS AND METHODS : Plasminogen activators ( t PA and u PA ) and their inhibitors ( PAI 1 and PAI 2 ) secretions were assayed in cultures of epithelial , stromal , and trophoblast cells . ^^^ RESULTS : The u PA from epithelial cells was predominant among PAs and PAI 1 in endometrial cells . ^^^ Progesterone ( P 4 ) suppressed u PA production in epithelial cells and enhanced PAI 1 production in both epithelial and stromal cells . ^^^ Trophoblasts produced PAI 1 , PAI 2 , and small quantities of t PA and u PA , none of which were notably influenced by E 2 or P 4 . ^^^ The PAI 1 production in trophoblasts was more than four fold greater than the u PA production in epithelial cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Furthermore , semiquantitative reverse transcription ( RT ) polymerase chain reaction ( PCR ) analysis of a panel of genes involved in the plasminogen activation system , including plasminogen activator inhibitor 1 ( PAI 1 ) , urokinase plasminogen activator ( u PA ) , and urokinase receptor ( u PAR 1 ) , demonstrated a significant upregulation ( approximately fourfold to sixfold , P < 0 . 05 ) in the expression of each of these genes in the tumor tissue . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Type 1 plasminogen activator inhibitor ( PAI 1 ) is the primary inhibitor of both tissue and urokinase type plasminogen activators ( t PA , u PA ) and is thus a primary regulator of plasminogen activation and possibly of extracellular proteolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
That is , MA 33H1F7 increased the stability of both PAI 1 / t PA and u PA complexes ( 7 and 3 fold , respectively ) whereas MA 55F4C12 stabilized PAI 1 / t PA complexes ( 3 fold ) but destabilized PAI 1 / u PA complexes ( 2 fold ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In this paper , we have studied the contribution of the plasminogen activation system in the development of atherosclerosis by cross breeding apoE 3 Leiden mice , which have a human like lipid profile , with mice deficient in PAI 1 ( plasminogen activator inhibitor 1 ) , u PA ( urokinase plasminogen activator ) , and t PA ( tissue plasminogen activator ) . ^^^ Lesion area of plaques in the aortic valve was not significantly different in apoE 3 Leiden : PAI / and apoE 3 Leiden : u PA / mice as compared to apoE 3 Leiden mice . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
METHODS : The mRNA steady state level of a large spectrum of proteolytic enzymes ( matrix metalloproteinases : MMP 1 , 2 , 3 , 8 , 9 , 11 , 12 , 13 , 14 ; urokinase plasminogen activator : u PA ) , their physiological inhibitors ( tissue inhibitors of MMPs : TIMP 1 , 2 , 3 ; plasminogen activator inhibitor : PAI 1 ) and that of structural matrix proteins ( collagens type 1 and 3 , decorin , elastin , fibrillins 1 and 2 ) was determined by RT PCR made quantitative by using a synthetic RNA as internal standard in each reaction mixture . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The type 1 plasminogen activator inhibitor ( PAI 1 ) , the primary inhibitor of both tissue type and urokinase type plasminogen activators ( t PA , u PA ) , is the primary regulator of plasminogen activation and possibly of extracellular proteolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Immunohistochemical and in situ hybridization studies of the expression of the direct activators of MMP 2 , MT 1 MMP and MT 3 MMP , and the indirect activation system tissue plasminogen activator , urokinase ( u PA ) , its receptor ( u PAR ) , and its inhibitor PAI 1 after middle cerebral artery occlusion / reperfusion were undertaken in basal ganglia samples from 26 adolescent male baboons . ^^^ The expressions of all three MMPs , u PA , u PAR , and PA 1 1 , but not tissue plasminogen activator , were increased from 1 hour after middle cerebral artery occlusion in the ischemic core . mRNA transcripts confirmed the increases in latent MMP 2 , u PA , u PAR , and PAI 1 antigen very early after middle cerebral artery occlusion . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Components of the plasmin system including tissue plasminogen activator ( t PA ) , urokinase plasminogen activator ( u PA ) , and plasminogen activator inhibitors PAI 1 and PAI 2 are synthesised by airway cells , and inflammatory mediators affect their expression . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrinogen binding potentiates FGF 2 but not VEGF induced expression of u PA , u PAR , and PAI 1 in endothelial cells . ^^^ The pericellular proteolytic balance is important in these responses , and FGF 2 and VEGF up regulate endothelial cell u PA , u PAR and PAI 1 . ^^^ Changes in mRNA levels of u PA , u PAR and PAI 1 were measured by Northern blot . ^^^ FGF 2 increased u PA , u PAR , and PAI 1 mRNA , but there was a significantly greater induction when fibrinogen was added to FGF 2 at all concentrations . ^^^ VEGF also increased endothelial cell expression of u PA , u PAR and PAI 1 , but this effect was not potentiated by fibrinogen . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Quantitative gene expression analysis ( real time RT PCR ) was performed for tissue factor ( TF ) , TF pathway inhibitor ( TFPI ) , tissue type plasminogen activator ( t PA ) , urokinase type PA ( u PA ) , PA inhibitor 1 ( PAI 1 ) , and PAI 2 in peripheral white blood cells ( PBC ) as well as in alveolar macrophages ( AM ) , type 2 pneumocytes ( ATII ) , endothelial cells ( EC ) and smooth muscle cells ( SMC ) , all obtained by laser microdissection . ^^^ Intraalveolar endotoxin , in particular , caused strong upregulation of TF ( approximately 20 fold increase in gene expression ) and PAI 2 ( 225 fold increase ) in microdissected AM , upregulation of PAI 1 in microdissected ATII ( 300 fold increase ) and EC ( 180 fold increase ) , upregulation of t PA in EC ( 40 fold ) , and downregulation of u PA in vascular smooth muscle cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Therefore , the consequences of transverse aortic banding ( TAB ) were analyzed in mice lacking tissue type PA ( t PA ( / ) ) , urokinase type PA ( u PA ( / ) ) , or gelatinase B ( MMP 9 ( / ) ) , and in wild type ( WT ) mice after adenoviral gene transfer of the PA inhibitor PAI 1 or the MMP inhibitor TIMP 1 . ^^^ In contrast , in u PA ( / ) mice or in WT mice after PAI 1 and TIMP 1 gene transfer , cardiomyocyte hypertrophy was moderate and only minimally associated with cardiac fibrosis and LV dilatation , resulting in better preservation of pump function . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Inflammatory markers ( tumour necrosis factor alpha , interleukin 8 , polymorphonuclear elastase ) , fibrinolytic system variables ( tissue plasminogen activator ( PA ) , urokinase PA ( u PA ) , plasminogen activation inhibitor ( PAI ) 1 , PAI 2 ) , and several MMPs ( MMP 1 , MMP 2 , MMP 8 , MMP 9 ) and TIMPs ( TIMP 1 , TIMP 2 ) were determined by ELISA in plasma and pleural fluid . ^^^ In parapneumonic effusions , MMP 1 , MMP 8 and MMP 9 showed a positive correlation with the inflammatory markers and with u PA and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
GCF levels of tissue type PA ( t PA ) , urokinase type PA ( u PA ) , PA inhibitor 1 ( PAI 1 ) and PA inhibitor 2 ( PAI 2 ) and serum concentrations of cotinine , u PA and PAI 1 were analysed by enzyme linked immunosorbent assay . ^^^ The ratio of u PA : PAI 1 and t PA : PAI 1 were significantly higher in GCF of smokers with periodontitis compared with `` healthy ' ' smokers , whereas the ratio of t PA : PAI 2 was significantly lower in smokers with periodontal disease ( p < 0 . 05 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The notion that OSM favors matrix stabilization in the human heart is further supported by our earlier observation that OSM also upregulates PAI 1 , the physiological inhibitor of the protease urokinase type PA ( u PA ) , which in turn is essential for extracellular proteolysis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
We demonstrate that KS cells and MVEC express the u PA receptor ( u PAR ) and release plasminogen activators and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ These data indicate that the u PA / u PAR / PAI 1 system is involved in KS induced endothelial cell invasion , proliferation , and differentiation . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The results showed that cyanidin 3 glucoside and cyanidin 3 rutinoside treatments could decrease the expressions of matrix matalloprotinase 2 ( MMP 2 ) and urokinase plasminogen activator ( u PA ) in a dose dependent manner and enhance the expression of tissue inhibitor of matrix matalloprotinase 2 ( TIMP 2 ) and plasminogen activator inhibitor ( PAI ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Both urokinase plasminogen activator ( u PA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) are associated with a poor prognosis in cancer patients . ^^^ An integrin antagonist , RGD peptide , and anti alpha ( 5 ) beta ( 5 ) integrin antibodies , which similarly inhibited cell attachment to Vn , also stimulated cell migration from Vn toward Col . u PA did not modify cell attachment directly , but reversed the PAI 1 mediated inhibitory effect on cell adhesion to Vn , and its stimulatory effect on cell migration from Vn toward Col . ^^^ Thus HT 1080 cell migration appears to be modified by u PA and PAI 1 , altering cell adhesion to Vn via alpha ( 5 ) beta ( 5 ) integrin . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Tumor associated prognostic factors of the plasminogen activator family : determination and clinical value of u PA , t PA , PAI 1 , and PAI 2 ] . ^^^ Proteolytic factors belonging t the plasminogen activator family ( plasmin , u PA , t PA , u PAR , PAI 1 , and PAI 2 ) , which usually are involved in blood clotting and degradation of blood clots , are also present in healthy and diseased tissue of the kidney , lung , liver , gastro intestinal tract , breast , prostate , ovary , and brain . ^^^ Plasminogen activators u PA and t PA , their inhibitors PAI 1 and PAI 2 , and the u PA receptor ( u PAR , CD 87 ) are often elevated in solid malignant tumour tissues compared to their normal counterparts . ^^^ In breast cancer patients , an elevated tumour tissue extract antigen content of u PA , PAI 1 , and u PAR is associated with increased tumour aggressiveness and poor prognosis ; in contrary , an elevated content of t PA and PAI 2 indicates a favourable prognosis . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
OBJECTIVES : To evaluate urokinase plasminogen activator ( u PA ) , urokinase plasminogen activator soluble receptor ( su PAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) and tissue plasminogen activator ( t PA ) plasma levels in SSc patients ( pts ) versus healthy controls and their modulation by intravenous alphacyclodestrine ( Alprostadil ) . ^^^ METHODS : Plasma levels of u PA , su PAR , PAI 1 and t PA were measured in 40 SSc ( 34 lSSc and 6 dSSc ) pts and in 30 healthy controls . ^^^ Infusions of Alprostadil modulate u PA , su PAR , PAI 1 and t PA , restoring near normal levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Neonates born to mothers of either normal pregnancy or preeclampsia at term showed similar hemostatic changes with reduced fibrinogen , ATIII , t PA , u PA antigen , PAI 1 levels , and coagulation activation compared to their respective maternal plasma levels . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
While no difference was observed for the production of u PA and u PA activity in the supernatant , cell proliferation of SW / PAI 1 was slightly suppressed on the 7th day of incubation compared to parental cells . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
Fibrinolytic system components ( u PA , u PAR and plasminogen activator inhibitor ( PAI ) 1 ) were assayed by ELISA with cells treated with 0 . 5 microM and 1 microM RAL for 48 h . u PA activity was evaluated by zymography and a direct fibrinolytic assay . ^^^ RA synoviocytes treated with RAL showed , compared to basal , higher levels of PAI 1 ( 10 . 75 + / 0 . 26 versus 5 . 5 + / 0 . 1 microg / 10 ( 6 ) cells , respectively ; p < 0 . 01 ) , lower levels of u PA ( 1 . 04 + / 0 . 05 versus 3 . 1 + / 0 . 4 ng / 10 ( 6 ) cells , respectively ; p < 0 . 001 ) , and lower levels of u PAR ( 11 . 28 + / 0 . 22 versus 23 . 6 + / 0 . 1 ng / 10 ( 6 ) cells , respectively ; p < 0 . 001 ) . ^^^ RAL exerts anti proliferative and anti invasive effects on synoviocytes , mainly modulating u PAR and , to a lesser extent , u PA and PAI 1 levels , and inhibiting cell migration and proliferation . . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
This effect was associated with a reduced expression of MMP 2 and u PA , together with an enhanced expression of TIMP 2 and PAI 1 . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
In the absence of TGF beta 1 , the expression of thrombomodulin , the plasminogen activators u PA and t PA , and their inhibitor PAI 1 was significantly increased in the S / G2 compared to the G 1 phase . ^^^ Treatment of endothelial cells with TGF beta 1 , however , resulted in elevated expression of PAI 1 specifically in the S / G2 phase , while t PA and u PA increased to the same extent in both the G 1 and S / G2 phase . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
The central components of the PA system are the proteolytic activators , urokinase plasminogen activator ( u PA ) and tissue type plasminogen activator ( t PA ) , plasminogen ( plg ) and its degradation product , plasmin , together with the major inhibitors of this system , plasminogen activator inhibitor 1 and 2 ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and P05121 Pubmed SVM Score :0.0
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