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)

Plasma levels of tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen and t-PA/PAI-1 complex were measured in plasmas from 18 healthy subjects and 75 patients with various diseases (28 patients with haematological malignancies, 20 with thrombotic diseases, five with infectious diseases, four with liver diseases, ten with bleeding disorders and eight miscellaneous conditions). In addition, we studied ten patients with bleeding disorders after DDAVP infusion and 18 healthy subjects after venous occlusion. Plasma levels of t-PA antigen, PAI-1 antigen and t-PA/PAI-1 complex were increased in the patients compared with the healthy subjects. t-PA/PAI-1 complex levels correlated well with t-PA antigen levels and molar concentrations of t-PA antigen were similar to those of the t-PA/PAI-1 complex. Venous occlusion induced an increase in both t-PA antigen and PAI-1 antigen and the molar concentration of the t-PA/PAI-1 complex was equivalent to that of t-PA antigen. Following DDAVP infusion, the levels of t-PA antigen and t-PA/PAI-1 complex increased but PAI-1 antigen levels decreased, and the increase of t-PA antigen was greater than that of t-PA/PAI-1 complex. These findings indicate that PAI-1 antigen exceeds t-PA antigen in healthy subjects and in patients with various diseases. We conclude that part of the t-PA/PAI-1 complex is rapidly cleared from the circulation and that free t-PA increases after DDAVP infusion.
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PMID:Behaviour of tissue plasminogen activator, plasminogen activator inhibitor 1 and their complex in various disease states. 142 Aug 14

Growth of the human breast cancer cell line MCF-7 is known to be inhibited both by antiestrogens such as 4-hydroxytamoxifen (OHTAM) and by retinoic acid (RA). Uncloned MCF-7 cells (UNC) and two cloned sublines, one sensitive to antiestrogens (E-3) and the other resistant to them (RR), were used in this study. Growth of UNC and E-3 was inhibited by either OHTAM (10(-7) M) or RA (10(-6) M), and this inhibition could not be overcome by the simultaneous addition of estradiol. Subline RR, which was originally selected for resistance to tamoxifen, was resistant to both OHTAM and RA as measured by either growth in culture or colony forming ability. RR was resistant to RA at all concentrations tested between 10(-9) M and 10(-6) M. The inhibition of uncloned MCF-7 cells by RA was dose dependent between 10(-9) M and 10(-6) M. Subline E-3, however, exhibited a mixed response to RA. At 10(-9) M and 10(-8) M, growth was stimulated, but at 10(-7) M and 10(-6) M it was inhibited. The level of estrogen receptor was measured in the same experiment by using a whole cell assay. In the uncloned MCF-7 cultures and in both the RR and E-3 sublines the level of estrogen receptor was increased between 50 and 200% by RA. The production of plasminogen activator by MCF-7 cells is stimulated by estrogen. RA had a dual effect on plasminogen activator production. In the absence of estrogen, RA inhibited production below the unstimulated level, but in cells stimulated by estrogen, RA increased plasminogen activator production. The results reported here support possible interactions between the mechanisms by which cells respond to estrogen, antiestrogens, and retinoids.
Cancer Res 1992 Nov 15
PMID:Responses to retinoic acid of tamoxifen-sensitive and -resistant sublines of human breast cancer cell line MCF-7. 142 59

The study of the plasminogen-plasmin system has, in the past, contributed much to the understanding of fibrinolysis and thrombolysis. Attention is now focused on the role of the components of this system in many biologic functions. Findings of uPA, its receptor and its inhibitor in many tumor tissues and tumor cell lines, strongly implicate their involvement in tumor invasion, tumor cell proliferation and metastasis. The characteristics of the plasminogen activators, the uPA receptor and the plasminogen activator inhibitors as well as their expression and regulation in tumors and tumor cell lines are reviewed.
Cancer Metastasis Rev 1992 Nov
PMID:The plasminogen-plasmin system in malignancy. 142 20

Normal human fibroblast (i.e., GM2936B, GM2907A, and IMR-90) and cancer-prone human fibroblast (i.e., Fanconi's anemia, Bloom's syndrome, and Ataxia telangiectasia) cells demonstrated the induction of intracellular and extracellular levels of tissue-type plasminogen activator (t-PA) at 6 and 12 hr, respectively, following ionizing radiation. Induced t-PA enzymatic activities following ionizing radiation were blocked by actinomycin D treatments. t-PA enzymatic activities were induced over 14-fold in Ataxia telangiectasia cells, over 9-fold in Bloom's syndrome cells, and over 6-fold in Fanconi's anemia cells, as compared to normal human fibroblasts. Similarly, the induction of t-PA mRNA levels in cancer-prone cells were between 5- to 10-fold higher than those observed in normal cells following equitoxic doses of ionizing radiation. Temporal induction of t-PA mRNA levels for normal and cancer-prone human cells were consistent with quantifiable enzymatic activities. The elevated induction of an intracellular protease (i.e., t-PA) in cancer-prone human cells is reminiscent of an "SOS"-like response observed in yeast and bacteria.
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PMID:Enhanced induction of tissue-type plasminogen activator in normal human cells compared to cancer-prone cells following ionizing radiation. 144 36

Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases.
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PMID:Expression of the epidermal growth factor receptor gene in human brain metastases. 152 Apr 84

Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells.
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PMID:Demonstration of a possible link between high grade malignancy in dimethylbenz[a]anthracene-induced rat mammary carcinoma and increased urokinase plasminogen activator content. 152 Sep 14

Medroxyprogesterone acetate (MPA), which is widely used clinically as an anticancer steroid preparation, is a very useful drug that seldom causes severe side effects such as bone marrow suppression, and can be dispensed at the outpatient clinic for an oral administration at home to the advantage of QOL. Recently however, there have been several reports suggesting its relationship with thrombosis. We measured t-PA, protein C, factor X, AT III, TAT, plasminogen, PIC, fibrinogen, and D-dimer in 11 patients with gynecologic malignancies who are treated with MPA (600 mg/day) and 11 controls. Then we examined the effects of the drug on blood coagulation and fibrinolytic activities. No changes in these parameters clearly suggested thrombogenesis in either group at this measurement or during the observation period (17 months at the maximum). The present study found no remarkable abnormalities in the blood coagulation and fibrinolytic activities. Thus, to avoid the use of MPA to patients at risk is considered to be the most important precaution for prevention of thrombosis.
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PMID:[Effect of high-dose medroxyprogesterone acetate on coagulative and fibrinolytic factors in patients with gynecological cancers]. 153 83

Hormonal regulation of plasminogen activator expression in 7,12-dimethylbenz[a]anthracene (DMBA)--induced rat mammary carcinomas was studied both in vivo and in vitro and was compared to that in DMBA-mammary dysplasia induced in neonatally androgenised rats. The plasminogen activator activity in DMBA-mammary carcinomas, but not in DMBA-mammary dysplasia, was regulated by oestrogen. This suggests that expression of this enzyme is hormonally regulated in carcinoma cells. Furthermore, in two of six DMBA-mammary carcinoma groups classified in terms of hormonal treatment, plasminogen activator activity was not under the control of oestrogen. Thus, the present results suggest that at the time of carcinogenesis, the hormonal milieu determines the hormone sensitivities of the malignant cells.
Br J Cancer 1992 Apr
PMID:Hormone control of total plasminogen activator activity is specific to malignant DMBA-induced rat mammary tumours. 156 66

The production of metastasis appears to involve a number of different proteases including the urokinase form of plasminogen activator, cathepsin B, cathepsin D and various metalloproteases. Early data implicating these proteases in metastasis were mostly indirect and based on correlation studies in animal models. More recent work, using specific protease inhibitors and antibodies against proteases to block experimental metastasis, have provided more direct evidence that proteases play a role in cancer spread. In addition, transfection of genes encoding certain proteases increases the metastatic phenotype of the recipient cells. In human tumours, a number of different proteases also correlate with metastatic potential. It is concluded that certain proteases may be new prognostic markers in cancer as well as new targets for anti-metastatic therapy.
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PMID:The role of proteolytic enzymes in cancer invasion and metastasis. 158 84

Pancreatic carcinoma is associated with a high frequency of thrombosis. Most patients with thrombotic disease have a defective fibrinolytic defense system caused either by plasminogen activator deficiency, excess of plasminogen activator inhibitor (PAI-1), or a combination of the two. In the current series of 27 patients with pancreatic carcinoma, 17 had had deep vein thrombosis (DVT) since the onset of their malignant disease, and most were found to have high plasma concentrations of PAI-1 antigen and PAI-1 activity. Analysis of singleton samples from each patient yielded no correlation between previous DVT and currently high plasma PAI-1 concentrations. However, serial samples from 14 patients (8 of whom had histories of thrombosis) showed individual values varied sharply with time, with intermittent peaks both in PAI-1 antigen and PAI-1 activity for 11 of the 14 patients. Such variability may contribute to intermittently excessive hypercoagulability because of a relative reduction in fibrinolytic potential. These changes may predispose the patient to have thrombotic events in association with pancreatic carcinoma.
Cancer 1992 Jun 15
PMID:Peaks in plasma plasminogen activator inhibitor-1 concentration may explain thrombotic events in cases of pancreatic carcinoma. 159 81


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