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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activators (PA) have been reported to be associated with fibrinolysis. The amounts of PA in urine, plasma, and tissues of patients with renal cell carcinoma were determined by measuring the amounts of two kinds of antigens, urokinase type (u-PA) antigen and tissue type (t-PA) antigen, by highly sensitive enzyme-immunoassay. The u-PA antigen level in urine showed neither daily variation nor age-relationship. It was, however, significantly higher (164.2 +/- 93.5 x 10(2) U/gCr) in patients with renal cell carcinoma than in healthy subjects (56.8 +/- 22.4 x 10(2) U/gCr) (p less than 0.01). The amount of u-PA antigen in urine tended to be higher in patients with high grade or stage cancer than in those with cancer of low grade or stage, though not statistically significant. The u-PA antigen content in tissues appeared elevated in tumors (8.90 +/- 6.00 x 10(-1) U/g wet tissue) in comparison to normal renal cortex and medulla. However, the difference was not significant, as the cancer samples consisted of various tissue components including necrotic or hemorrhagic tissue in addition to cancer cells. Although the t-PA antigen content in urine was too immeasurably small in 29% cases by the present method, there was no significant difference between patients with renal cell carcinoma and healthy subjects. The plasma level of t-PA antigen tended to be elevated in renal cell carcinoma group (7.87 +/- 5.60 U/ml) compared to the control group (5.7 +/- 2.19 U/ml), but no significant difference was present between them.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The study of plasminogen activator in renal cell carcinoma with special remarks on urokinase type plasminogen activator]. 251 7

This report describes the development and use of functional immunoradiometric assays that distinguish the activity of beta-migrating endothelial-type plasminogen activator inhibitor (PAI-1) from that of placental-type plasminogen activator inhibitor (PAI-2). These assays are based upon the binding of PAI-1 and PAI-2 to immobilized single-chain tissue-type plasminogen activator (tPA) and to immobilized urokinase (UK), respectively. The extent of binding of each PAI is quantified by incubating the PAI-PA complex first with rabbit antiserum specific for the individual PAI and then with 125I-labeled goat antirabbit IgG. In control experiments, the assays were shown to be sensitive, dose-dependent over a wide range, and specific for each PAI. These assays were employed to establish the PAI profile of a variety of human cells. Neither PAI-1 nor PAI-2 could be detected in Bowes melanoma cells or in a renal adenocarcinoma cell line (ACHN), while the histiocytic lymphoma cell (U-937) produced only PAI-2. Five cell lines, including two that were previously shown to contain one or the other PAI (e.g., umbilical vein endothelial cells and a fibrosarcoma cell line, HT-1080) in fact contained both PAIs. The cells containing both PAIs were studied in more detail. In each case, SDS treatment of CM was shown to enhance PAI-1 activity (by converting the latent form of this inhibitor into its active form) and to destroy PAI-2 activity. Various compounds including interleukin 1, dexamethasone, and phorbol myristate acetate were found to selectively influence the cellular production of one PAI without concomitantly affecting the production of the other, suggesting that the synthesis of these inhibitors is not coordinately regulated.
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PMID:Detection of both type 1 and type 2 plasminogen activator inhibitors in human cells. 325 67

Dimethylsulfoxide, butyrate and retinoic acid, agents which induce differentiation of certain malignant cells, were examined for their effect on the activity of plasminogen activator (PA) of serumless conditioned medium (CM) of two human renal carcinoma cell lines. All three agents produced a decrease in PA activity. More than 90% of the PA was secreted in latent form, and this was not altered by the agents. Active PA components of Mr 52,000 and 93,000 were identified in cell secretions by zymography. In the presence of DMSO or butyrate the Mr 52,000 component was markedly reduced. Reversibility of the effect on PA was demonstrated for both DMSO and retinoic acid with activity of CM returning to control level after removal of the agent. That the effect was temporary agrees with most observations of the effects of these and similar agents on cells from solid tumors.
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PMID:Modulation of secreted plasminogen activator activity of human renal carcinoma cells by dimethylsulfoxide, butyrate and retinoate. 354 47

Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 micrograms/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 micrograms/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis.
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PMID:Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6. 788 14

The plasminogen activation system is considered to play an important role in cancer growth and metastasis. Both plasminogen activators (PAs) and their fast-acting inhibitors are produced in tumor cells and their surrounding tissues. In order to clarify the influence of the existence of malignant tumor in urinary tract on the systemic fibrinolytic activity, we designed a study in which we compared the plasma levels of PAs and their inhibitors between before and after radical resection of tumors. Fourteen patients with renal cell carcinoma and 14 patients with transitional cell carcinoma participated in the study. In both groups, plasma levels of tissue-type plasminogen activator and urokinase-type plasminogen activator before the operation were higher than those 15 days after operation. The plasma level of plasminogen activator inhibitor 1 (PAI-1), however, did not change after the operation in the renal cell carcinoma group, and it decreased slightly in the transitional cell carcinoma group although it was not significant. When these values of the groups with or without metastasis were compared to other organs or lymph nodes, the PAI-1 level before operation was significantly higher in the group with metastasis than that without metastasis. In the three groups divided by the degree of atypia, PAI-1 level in the most atypical group was the highest. These results suggest that the fibrinolytic system in the plasma of cancer patients may play an important role in tumor growth and metastasis.
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PMID:Plasminogen activators and plasminogen activator inhibitor 1 in urinary tract cancer. 814 Jun 79

In experimental models, plasminogen activator-mediated degradation of the extracellular matrix is inhibited by type-1 plasminogen activator inhibitor (PAI-1). PAI-1 has also been shown to protect tumour stromal tissue from autoproteolytic activities and may thus substantially promote tumour growth and metastasis formation. Human renal cell carcinoma (RCC) cells express significant amounts of plasminogen activator activity. In the present study, the expression of its specific inhibitor PAI-1 has been investigated in 32 cases of RCC and compared with adjacent non-tumour renal tissues. RCC tissue exhibited higher levels of PAI-1, determined at both the antigen and the mRNA level by ELISA and Northern blot analysis respectively. Immunohistochemical analysis showed that PAI-1 antigen was primarily confined to tumour cells and vascular endothelium, a distribution similar to that previously reported for plasminogen activator activity in RCC. The close co-localization with endogenous plasminogen activator activity may be important in the regulation of RCC-associated proteolysis. The increased expression of PAI-1 and its predominant localization within the tumour may help to conserve tumour tissue integrity and may thus promote RCC progression and metastasis formation.
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PMID:Type-1 plasminogen activator inhibitor in human renal cell carcinoma. 869 52

Cultured human mesangial cells (HMC) derived from normal kidneys have been shown to synthesize tissue-type plasminogen activator (t-PA) and excess amounts of PA inhibitor type 1 (PAI-1). 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. We evaluated the fibrinolytic profile of cultured HMC lines obtained from 12 patients with renal carcinoma and one cadaveric kidney donor. 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). Besides PAI-1, PAI-2 antigen was detected in all but one HMC lines. 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. PAI activity was found instead in the extracts in which the inhibitor was higher than the activator (six lines) and was identified as PAI-2, as it inhibited u-PA but not single-chain t-PA and was neutralized by a polyclonal anti-PAI-2 antibody. The heterogeneous fibrinolytic pattern of HMC lines was confirmed by mRNA analysis of three representative lines. Results were similar when HMC lines at passage five were used, except that the u-PA content was significantly reduced both in CM and CE. These findings indicate that the fibrinolytic profile of cultured HMC is more complex than previously reported. The production of large amounts of PAI-2 may represent an additional control mechanism of proteinase activity.
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PMID:Cultured human mesangial cells produce both type 1 and type 2 plasminogen activator inhibitors. 877 30

The binding of urokinase-type plasminogen activator (u-PA) to a specific cell surface receptor (uPA-R) has been shown to enhance plasminogen activation, a process involved in extracellular matrix degradation and cell migration during angiogenesis and tumor growth. We investigated the expression of u-PA and uPA-R in renal cell carcinomas (n = 11). By immunohistochemistry using monoclonal and polyclonal anti-uPA-R antibodies, we found that tumoral capillary endothelial cells (von Willebrand factor and CD31 positive cells) overexpressed uPA-R, whereas vascular endothelial cells of the normal human kidney do not. In addition, tumor-associated macrophages (CD68-positive cells) strongly expressed uPA-R. In contrast, few tumoral cells and stromal fibroblasts expressed uPA-R. By in situ hybridization using a cDNA S35-labeled probe specific for uPA-R, we confirmed the local expression of uPA-R messenger RNA. We also detected the induction of u-PA in tumoral capillary endothelial cells and in tumor-associated macrophages. In two cases, tumoral cells themselves were also stained by anti-u-PA antibodies in focal areas. Finally tissue-type plasminogen activator (t-PA) was also overexpressed by tumoral capillary endothelial cells as compared with endothelial cells of normal human kidney vessels. These findings indicate an active invasive phenotype of endothelial cells in renal cell carcinoma and suggest a role for the plasminogen activation system in tumoral angiogenesis and invasion.
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PMID:Endothelial and macrophage upregulation of urokinase receptor expression in human renal cell carcinoma. 902 4

A 67-year-old male became anuric immediately after a right radical nephrectomy for renal cell carcinoma. The patient was diagnosed with an acute arterial thrombosis of the remaining kidney within 4 hours after surgery by both CT scan and angiography. Thrombolytic therapy was started by a transcatheteral infusion of tissue-type plasminogen activator (TPA) resulting in a complete recanalization. Hydration and systemic administration of heparin followed, and renal function recovered within 3 weeks. This is the first report of acute thrombosis in a contralateral renal artery immediately after a radical nephrectomy which was successfully treated with TPA. It is probable that compression of the contralateral renal artery by the retractor for an extended period of time during surgery led to this unfavorable condition.
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PMID:Acute thrombosis in a contralateral kidney after radical nephrectomy: successful treatment by thrombolytic therapy using a tissue-type plasminogen activator. 917 May 84

AE-941 (Neovastat) is a naturally occurring product extracted from cartilage and has antiangiogenic properties. It has reached Phase III clinical trial evaluation for the treatment of solid tumors (non-small cell lung cancer and renal cell carcinoma) and a pivotal Phase II clinical trial in multiple myeloma is ongoing. AE-941 inhibits several steps of the angiogenesis process, including matrix metalloproteinase activities and VEGF signaling pathways. Moreover, AE-941 induces endothelial cell apoptosis and tissue-type plasminogen activator activity, thus suggesting that it is a multifunctional antiangiogenic drug. Results from Phase I/II clinical trials indicate that AE-941, given orally, is well tolerated. Moreover, the median survival time in patients with renal cell carcinoma and non-small cell lung cancer was significantly longer in patients receiving high doses of AE-941 compared to low doses.
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PMID:AE-941 (Neovastat): a novel multifunctional antiangiogenic compound. 1211 1


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