Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This laboratory recently reported that laminin degradation by cultured colon cancer was plasminogen dependent and reflected the presence of urokinase bound to cell surface receptors. (Schlecte, W.; Murano, G.; Boyd D. Cancer Res., 49:6064-6069; 1989). The present study was undertaken to determine the sensitivity of urokinase receptor directed proteolysis to the type I plasminogen activator inhibitor (PAI-1). Colon cancer cell types, that were highly effective in degrading laminin in vitro, elaborated into their conditioned medium an inhibitor which was indistinguishable from PAI-1 on the basis of its performance in reverse zymography, western blotting, and immunoprecipitation assays. A fraction of this PAI-1 was active, as evidenced by complex formation with the active site of radioactive urokinase. Laminin degradation by the colon cancer cells, however, did not appear to be affected by the endogenous inhibitor, since an antibody to the inhibitor, which blocked urokinase-PAI-1 interactions, had little effect on laminin turnover. Further, addition of exogenous PAI-1, activated by guanidine hydrochloride pretreatment, to the colon cancer cells did not perturb laminin degradation. Because laminin degradation by colonic cells was a function of receptor bound urokinase, presumably immobilized plasminogen activator escaped the neutralizing effect of the inhibitor. These data suggest either a shielding effect of the receptor on the plasminogen activator or a physical separation of activator and inhibitor. Either way, for cultured colon cancer at least, laminin degradation directed by urokinase receptor bound plasminogen activator appeared unaffected by the presence of this inhibitor.
Cancer Commun 1990
PMID:Insensitivity of laminin degradation directed by receptor bound urokinase to PAI-1 in cultured colon cancer. 239 Apr 19

Fibrinolytic activity in the blood of rats during the development of Guerin epithelioma was studied. It was measured by means of radiometric method, based on the amount of plasmin degradation products released from 125I-fibrin, as well as by means of amidolytic technique with the use of Chromozym PL. During the initial phase of epithelioma development the fibrinolytic activity of plasma, determined after inactivating plasma proteinase inhibitors, increases. It also increases in the euglobulin fraction. Simultaneously, the content of fibrin(ogen) degradation products (FDP) increases in the blood. During the stage of the intensive development of neoplastic disease fibrinolytic activity as well as plasminogen activator activity become inhibited, whereas the concentration of FDP retains the level observed in healthy animals. Inhibition of fibrinolytic activity in the later phase of the disease coincides with the appearance of low-molecular weight antifibrinolytic factor in the blood of rats loaded with epithelioma.
Cancer Lett 1990 Aug
PMID:Fibrinolytic activity of rat plasma during development of Guerin epithelioma. 239 83

The presence and localization of the plasmin system components urokinase (UPA), tissue type plasminogen activator (TPA), plasminogen (PG), a neoantigen expressed by the plasmin-alpha 2-antiplasmin complex, and plasmin inhibitors alpha 2-antiplasmin (AP) and alpha 2-macroglobulin (MG) have been tested by immunofluorescence on sections of 11 benign and 40 malignant lesions of the breast in an attempt to apply a morphological approach to the problem of tumor invasion in vivo. In benign lesions, TPA was seen in secretions of mammary glands and MG was seen in edematous zones. In one involuting lactating adenoma, UPA, TPA, PG, PAP, and AP were associated with glandular cells. UPA was detected in 11 carcinomas, TPA in 22, PG in 31, PAP in 12, AP in 23, and MG in all 40. All these components were essentially present in invasive territories, with a cellular labeling for UPA and TPA and a fluorescent staining frequently at the periphery of tumoral foci for PG and PAP. AP was more closely associated with cancer cells than MG, which was present in the stroma. Intraductal proliferations were rarely positive and there was no correlation between the localization of PG and the distribution of a basement membrane glycoprotein laminin. These data argue strongly for the involvement of the plasmin system in the infiltrating process of the stroma. This system seems to play a limited role in the breakdown of basement membrane in breast carcinomas in vivo.
Cancer Res 1986 Nov
PMID:Detection of the plasmin system in human mammary pathology using immunofluorescence. 242 83

Treatment of tumor cells that have little if any metastatic potential with certain drugs that have little or no mutagenic activity has been found to result in marked phenotypic alterations of the cells, including development of a metastatic potential. We found that polar compounds and butyric acid, which are known to alter the expressions of normally silent genes, enhanced the lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells. This change was accompanied by increases in the activities of degradative enzymes such as glycosidases, cathepsin B, and plasminogen activator; adhesion of the cells to culture dishes, monolayers of endothelial cells, and a subendothelial matrix; and homotypic aggregation. The effects of these drugs in enhancing the lung-colonizing ability of the cells was found to be reversible, suggesting that it was due to epigenetic alterations. Other investigators have shown that treatment of nonmetastatic tumor cells with 5-azacytidine, which causes hypomethylation of DNA and activates normally silent genes, results in the emergence of a small number of clones with a heritable but unstable metastatic phenotype. These findings suggest that epigenetic mechanisms are involved in rapid cellular phenotypic diversification and tumor progression.
Cancer Metastasis Rev 1986
PMID:Modification of the metastatic potential of tumor cells by drugs. 243 28

To assess the postulated correlation between plasminogen activators (PAs) and malignancy, we determined the mRNA content for urokinase-type (u-PA) and tissue-type (t-PA) enzymes in a prospective series of 29 primary lung and 27 primary breast carcinomas. Dot blots of total RNAs were hybridized with appropriate cRNA probes under conditions that allow quantitative measurement of the mRNA level for each PA. Most tumors (43 of 56) had a u-PA mRNA content higher than the mean + 1 SD of nonmalignant tissue counterparts. A large, 4- to 20-fold, increase in u-PA mRNA content was demonstrated in 14 of 29 lung carcinomas and in 10 of 27 breast carcinomas. A statistically significant correlation (Fisher's test, P = 0.007) was found between elevated u-PA mRNA content in lung carcinomas and the presence of regional lymph node metastases. These results are consistent with a role for u-PA in tumor invasiveness and metastatic propensity and may have important prognostic and therapeutic implications.
Cancer Res 1987 Aug 01
PMID:Increase of urokinase-type plasminogen activator gene expression in human lung and breast carcinomas. 244 May 56

Clinical trials of recombinant biologic agents have resulted in new treatment options for hematologic, oncologic, and cardiologic disorders. These agents include the interferons, recombinant human erythropoietin (r-HuEPO), colony-stimulating factors (CSFs), interleukins (ILs), and tissue plasminogen activator (t-PA). Interferon alfa has proven efficacious in treating certain hematologic malignancies and solid tumors and has recently been indicated for acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Treatment with r-HuEPO has relieved the chronic anemia of hemodialysis patients. Recombinant human granulocyte CSF (G-CSF) or human granulocyte macrophage CSF (GM-CSF) has been used to treat patients after autologous bone marrow transplantation for lymphoid or solid malignancies, resulting in increased production of granulocytes and platelets. G-CSF and GM-CSF have been used to treat aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with AIDS. In patients with evolving myocardial infarction, the recombinant agent t-PA has proved more efficacious than streptokinase in terms of average coronary artery patency rates and survival rates in patients with evolving myocardial infarction. While these agents all offer promising therapeutic advances, the expenses associated with developing and testing biotherapeutic substances have resulted in high treatment costs. Since in many instances investigational therapy is the best treatment option available, physicians, patients, the pharmaceutical industry, the government, and insurance carriers must work together to ensure that these therapies are financially available to those in need.
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PMID:New directions in hematologic biotherapy. 247 3

Medroxyprogesterone acetate (MPA) is an anti-cancer drug for mammary carcinomas and an angiostatic steroid. The effects of MPA on the growth and plasminogen activator (PA) activity of bovine endothelial cells were investigated to elucidate the inhibitory mechanism observed in angiogenesis. MPA did not suppress the growth of capillary endothelial cells, even at high concentrations. On the other hand, in bovine endothelial cells of 3 types (adrenal cortical capillary, aortic and pulmonary artery endothelial cells), MPA inhibited extracellular and cell-associated activity of PA, which might be a protease involved in the neovascular response. MPA also greatly inhibited the high level of PA induced by basic fibroblast growth factor (FGF). The same result was obtained when PA production was induced by 4 beta-phorbol-12-myristate-13-acetate (PMA) in endothelial cells. These findings suggest that one of the points of inhibitory action of MPA in the process of angiogenesis may be the suppression of PA activity, and that inhibition of this protease might be useful for reduction of tumorigenic or excessive angiogenesis in vivo.
Int J Cancer 1989 Nov 15
PMID:Medroxyprogesterone acetate, an anti-cancer and anti-angiogenic steroid, inhibits the plasminogen activator in bovine endothelial cells. 247 7

We have developed a highly sensitive sandwich enzyme immunoassay for determination of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) antigen levels in extracts of human tissues. We determined antigen levels of PAs in extracts of 31 primary cancers and 15 normal mucosal tissues of the urinary bladder using this method. U-PA antigen levels in extracts of bladder cancers were significantly higher than those in normal tissues (p less than 0.005). U-PA antigen levels significantly increased as histological grading of malignancy advanced. There was no correlation between t-PA antigen level and malignancy. These results indicate that an increase of u-PA antigen level may be a parameter of malignant transformation and may play an important role in invasiveness of cancer.
Cancer Res 1989 Feb 15
PMID:Comparative study of plasminogen activators in cancers and normal mucosae of human urinary bladder. 249 5

We have analyzed the plasminogen activator (PA) systems of two metastatic breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, as a function of 17 beta-estradiol stimulation when the cells were cultured on purified components of extracellular matrix. Laminin enhanced PA levels in both cell lines, but this enhancement seemed to occur via different mechanisms, including dissociation of inhibitor complexes. The major effect was the marked increase in cell-associated urokinase-type PA (u-PA); the increase was independent of estrogen in hormone-insensitive MDA-MB-231 cells grown on laminin-coated surfaces. In estrogen-sensitive MCF-7 cells, 17 beta-estradiol stimulated u-PA secretion in a similar fashion on plastic, laminin, fibronectin, or collagen but acted in synergy with laminin in the production and release of tissue-type PA.
J Natl Cancer Inst 1989 Feb 15
PMID:Modulation of plasminogen activator systems by matrix components in two breast cancer cell lines: MCF-7 and MDA-MB-231. 249 46

Using specific assays, we studied fibrinolytic activity in plasma and colonic mucosa biopsies of 28 patients with inflammatory bowel disease (IBD) (12 with Crohn's disease, 16 with ulcerative colitis) and 28 control patients without inflammatory bowel disease or colon malignancy. Blood coagulation was studied using standard techniques. In plasma of IBD patients significantly decreased tissue type plasminogen activator activity (t-PA) (p less than 0.02), increased plasminogen activator inhibition (PAI) (p less than 0.01) and fibrinogen (p less than 0.001), and prolonged thrombin time (p less than 0.001) and prothrombintime (p less than 0.001) were found. In colon mucosa the percentage of t-PA to urokinase type plasminogen activator (u-PA) was 80:20% in the control group and 71:29% in the IBD group in non-inflamed mucosa. In inflamed mucosa the plasminogen activator percentage was 55:45%, significantly different (p less than 0.01) from the control group. There was also a significant absolute increase in u-PA activity and decrease of t-PA activity in the inflamed mucosa compared to the control group (p less than 0.001 and p less than 0.01, respectively). Patients with inflammatory bowel disease therefore have significant changes in components of the fibrinolytic and coagulation system both systemically and locally in colon mucosa. These changes might contribute to an increased risk for thromboembolic complications and possibly to the pathogenesis of the colitis and to the local complications such as bleeding.
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PMID:Disturbed fibrinolysis in patients with inflammatory bowel disease. A study in blood plasma, colon mucosa, and faeces. 280


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