Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of alpha 2PI-plasmin complex and tissue-type plasminogen activator (t-PA) in plasma were determined in 10 cases of acute promyelocytic leukemia (APL) with marked coagulopathy and in 10 cases of hematological malignancies with DIC to investigate relevance to fibrinolysis. In the both groups, levels of alpha 2PI-plasmin complex increased and were inversely proportional to levels of fibrinogen and alpha 2PI. Levels of t-PA in plasma increased moderately in the majority of the both groups. Serial observation of the concentrations of t-PA with corresponding changes in the levels of fibrinogen, alpha 2PI, alpha 2PI-plasmin complex and FDP could not demonstrate any significant relationship between levels of t-PA and the other parameters. From these results, it is unlikely that levels of t-PA in plasma directly influence on the degree of consumption of alpha 2PI or of formation of alpha 2PI-plasmin complex in most cases of DIC.
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PMID:Changes in levels of t-PA and alpha 2PI-plasmin complex in plasma in patients with DIC. 314 64

Diffuse defibrination is rarely observed in acute lymphoblastic leukemia (ALL). Clinical and immunologic data suggest that it is more likely to occur in T cell derived ALL. The current investigation involved the secretion of plasminogen activators (PA) of tissue type (t-PA) or urokinase type (U-PA) by testing supernatants of 21 permanent human leukemic cell lines originating from various hematopoietic lineages and one induced lymphoblastoid cell line. (LCL) The amount of PA in each supernatant was determined by biologic and immunoenzymologic assays. The correspondence with the expected molecular weight (MW) according to the PA type was checked by zymography. PA secretion of U-PA type was observed in the three myeloid cell lines. Except for the normal LCL, no B-lymphoid lineage related cell lines of various levels of differentiation displayed PA secretion, whereas PA activity was observed in the supernatant of six of nine malignant T-cell lines. The T-leukemic cell lines CCRF CEM, KE 37, HUT 78, and HUT 102 released U-PA-like activity. Peer released t-PA-like activity and CCRF-HSB2 supernatant showed both types of PA activity. These findings are discussed in view of the natural history of these diseases and the stage of differentiation of the cell lines.
Cancer 1988 Nov 01
PMID:High frequency of plasminogen activator secretion by malignant human lymphoid cell lines of T-cell type origin. 316 7

The correlation between malignant transformation and increased PA synthesis or secretion has been examined in a variety of cell lines. To study the relationship between content and composition of PAs and colorectal neoplasms, we measured u-PA and t-PA antigen levels in normal mucosa, tubular adenoma, adenocarcinoma in adenoma, and adenocarcinoma, using a sensitive sandwich enzyme immunoassay. This assay was very sensitive and was not hindered by the presence of serine protease inhibitors. Both adenomas and carcinomas had higher u-PA antigen levels than normal mucosa. The u-PA antigen level of adenomas was lower than that of carcinomas. Antigen level of t-PA, however, was lower in both adenomas and carcinomas compared with that in normal mucosa, the values being lowest in carcinomas. Two cases of carcinoma in adenoma had PA contents similar to those of carcinomas. u-PA antigen level of adenomas with dysplastic epithelium was higher than that of adenomas without dysplastic epithelium. Therefore, the increase of u-PA content in adenomas could be a parameter of malignant changes in adenomas.
Int J Cancer 1988 Oct 15
PMID:Comparative study of plasminogen activator antigens in colonic carcinomas and adenomas. 317 33

Human endometrial adenocarcinoma HEC-1-A and HEC-1-B cells produce and secrete the urokinase-type plasminogen activator and trace amounts of the tissue-type plasminogen activator. The two clones, which originate from the same tumor, possess high affinity binding sites for basic fibroblast growth factor (bFGF) and they respond to the addition of human recombinant bFGF with an increase of the synthesis and secretion of urokinase-type and tissue-type plasminogen activators and with an increase in cell proliferation. Transforming growth factor beta, (TGF beta), when added alone or 6 h before bFGF, induces an increase of plasminogen activator synthesis in both cell lines and stimulates the production of the endothelial cell-type plasminogen activator inhibitor in HEC-1-A cells, but not in HEC-1-B cells. Moreover, TGF beta inhibits basal proliferation of both cell lines and suppresses the mitogenic activity of bFGF. We have previously demonstrated that HEC-1-A and HEC-1-B cells produce significant amounts of bFGF. On the basis of the well-established coordinate modulation of solid tumor growth and plasminogen activator production, our data suggest that bFGF may contribute, in an autocrine fashion, to the development of endometrial carcinomas. Moreover, endometrial tumor cells appear also to be a target for TGF beta. Our results demonstrate also that significant qualitative and quantitative differences in the response to growth factors exist in clones derived from the same tumor, and support the view that the properties of in vivo tumors cannot be extrapolated from results obtained with a single isolate of tumor cells.
Cancer Res 1988 Nov 15
PMID:Modulation of plasminogen activator activity in human endometrial adenocarcinoma cells by basic fibroblast growth factor and transforming growth factor beta. 326 85

We have analyzed the CM of 20 human tumor cell lines for the presence of PA, PA-I and PC. Most of the cell lines expressed PA activity as measured by a radioiodinated fibrin plate assay. The urinary type and tissue-type PA activities were specifically quantified by means of purified inhibitory antibodies. U-PA and/or t-PA antigen, as measured by radioimmunoassays, were detected in all but 4 of the CM and were generally 10 times more concentrated than PA activity, indicating the presence of specific PA-Is. Analysis of CM by electrophoresis followed by fibrin-agarose zymography demonstrated the presence not only of free but also of inhibitor-complexed PA. Affinity purification demonstrated that 8/20 cell lines expressed detectable PA-I activity. The PA-I1 and PA-I2 inhibitors were most frequently observed, while PN was recovered only from CM of the HT1080 fibrosarcoma cell line. PC activity, as measured by the plasma recalcification time method, was found in 9/20 CM. It was of the thromboplastin tissue factor type since most of its activity was lost when assayed with a Factor VII-deficient plasma.
Int J Cancer 1986 Nov 15
PMID:Plasminogen activators, plasminogen activator inhibitors and procoagulant analyzed in twenty human tumor cell lines. 349 Apr 46

Malignant changes are often accompanied by alterations in activity and composition of the plasminogen activators (PA). To study the relationship between PA expression and the development of colorectal cancer, we determined urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) activity in normal mucosa (n = 80), adenomatous polyps (n = 76), and adenocarcinomas (n = 71) of the colon. Tissues obtained from surgical resection or polypectomy were analyzed for t-PA and u-PA activity in a specific enzymatic assay using plasminogen, a chromogenic substrate, and selective quenching with monospecific antibodies to both activators. The plasminogen activator activities were found to be changed in adenocarcinomas as compared to normal mucosa. The relative contribution of u-PA (expressed as percentage of u-PA) was raised from 6 to 50% for, respectively, normal mucosa and adenocarcinoma. This change could be attributed to a 3-fold decrease in t-PA activity and a 5-fold increase in u-PA activity in the carcinomas. Adenomatous polyps as a group showed percentages of u-PA [20.2 +/- 1.3 (SE)] which were intermediate as well as significantly different (P less than 0.001) from those of normal mucosa and adenocarcinomas. This observation was strengthened by a gradual rise in the relative contribution of u-PA in four resection specimens containing both adenomatous polyps and adenocarcinomas. Zymography showed the presence of minor quantities of PA-PA inhibitor complexes in the tissue extracts studied. The present study shows that the sequence of normal mucosa-adenomatous polyp-adenocarcinoma in the colon is associated with a parallel change in plasminogen activator activity. Thus, change in the regulation of plasminogen activator activity is an early event in the development of colorectal cancer.
Cancer Res 1987 Sep 01
PMID:Plasminogen activators and tumor development in the human colon: activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas. 362 Nov 60

The immunoperoxidase technique, using antibodies against human urinary urokinase (Mr 55,000), was used for the localization of this enzyme in histological preparations of human colon tumors and normal colon tissue. The localization of tissue (vascular) activator was also investigated using antibodies against enzyme purified from human malignant melanoma. Both the "indirect method" and the peroxidase-antiperoxidase technique were found to be useful. Urokinase-reactive material was found in all tissues examined (33 primary cancers, 11 metastases, and 8 adenomas). In the normal colon, urokinase was found only in some of the goblet cells of the mucosal epithelium. In colon cancer, diffuse specific staining was observed in the cytoplasm, but the most intense staining was localized at the edge of the cancer cells bordering the lumen of the glands. In some cases, intense supranuclear staining could be observed in a location corresponding to the Golgi apparatus. In a few instances, urokinase could be seen associated with fibroblasts near the advancing front of an invading tumor. Adenoma, a benign tumor but often a precursor of cancer, also showed the presence of urokinase. Most significant were the observations showing that, in regions of the mucosal glands where normal epithelial cells were abruptly replaced by cancer cells, the appearance of cytoplasmic urokinase showed strict and exclusive association with the malignant cells, and the same was the case in transitions from normal epithelium to adenoma. In contrast to urokinase, tissue plasminogen activator was not associated with cancer cells, but was consistently present in the stroma which separates the cancer glands and was localized in the endothelium of the blood vessels. This visual evidence was supported by results of extraction of plasminogen activators from tumors, and from the separated mucosal and submucosal layers of the normal colon of the same patients, which showed that urokinase is most abundant in the tumor tissue and least abundant in the submucosa, while tissue activator is most prevalent in the well-vascularized mucosa and submucosa and scarce in the usually poorly vascularized adenocarcinomas.
Cancer Res 1985 Apr
PMID:Localization of plasminogen activators in human colon cancer by immunoperoxidase staining. 388 45

Eighteen patients with renal-cell carcinoma have been investigated in an attempt to elucidate the ratio of active urokinase enzyme to urokinase antigen in the tumor and adjacent normal kidney. The tumor itself exhibited a significantly increased total fibrinolytic activity, an increase in the relative contribution of anti-urokinase IgG-inhibitable plasminogen activator activity and increased levels of urokinase antigen when compared to normal renal tissue. In tumor-adjacent tissue total fibrinolytic activity was also, but not significantly, increased, this increase being completely due to tissue-type plasminogen activator. Correlation of active urokinase-type plasminogen activator with urokinase antigen revealed that in tumor tissue the enzyme was present to more than 70% in its active form whereas in tumor-adjacent tissue and normal renal tissue only half of the enzyme appeared to be active. No correlation was obtained between urokinase antigen present in one of the 3 tissues investigated and plasma urokinase antigen.
Int J Cancer 1985 Jun 15
PMID:Increased urokinase activity to antigen ratio in human renal-cell carcinoma. 392 43

19 patients with carcinoma of the prostate and 6 controls with hyperplasia of the prostate, have been investigated to elucidate the relationship between tumor fibrinolytic activity, the degree of malignancy, tumor stage and metastatic spread. Significantly (p less than 0.001) higher tissue plasminogen activator activities were found in metastatic carcinoma compared to nonmetastatic carcinoma or hyperplasia of the prostate. Antibodies against human urokinase caused inhibition of urokinase and plasminogen activator activity from human prostatic carcinoma or hyperplasia. Antibody inhibition studies as well as physicochemical characteristics of the plasminogen activator produced by prostatic hyperplasia and carcinoma tissue indicate that this plasminogen activator is identical or similar to urokinase.
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PMID:Tissue plasminogen activator activity in prostatic cancer. 608 49

In the present paper we have characterized the plasminogen activators (PA) synthesized by 25 different human cell lines. Technically easy methods were adopted for concentration and immunological characterization of the activators even in the presence of PA inhibitors. Most cell lines produced u-PA (mol. wt 55,000), melanoma and HeLa cells t-PA (mol. wt 66,000) and two carcinoma cell lines and normal skin fibroblasts produced no detectable PA. The classical 125I-fibrin method was compared to a caseinolytic assay and some of the discrepancies between results obtained with the two methods were shown to be due to cell-derived NaDodSO4-sensitive proteinase inhibitors in culture media. Additionally, synthesis and uptake by the cells of the wide-spectrum proteinase inhibitor alpha-2-macroglobulin ( alpha 2M ) were studied by radioimmunoassay and immunofluorescence. No production of alpha 2M could be measured in any of the malignant cell lines. In normal cells no correlation existed between the production of alpha 2M and the observed inhibition of PA activity, which indicates that other proteinase inhibitors are produced by the cells.
Int J Cancer 1984 May 15
PMID:Plasminogen activators, activation inhibitors and alpha 2-macroglobulin produced by cultured normal and malignant human cells. 620 45


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