Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The value of the oral anticoagulant warfarin sodium and fibrinolytic agents is discussed in relation to cancer surgery. A controlled trial of 128 patients showed that in a variety of recurrent cases the addition of warfarin to chemotherapy doubled the 2-year survival rate. The best results were obtained in postmenopausal patients with breast cancer. Warfarin depresses cellular immune responses which might militate against its use for cases undergoing "curative" surgery. Instead, induction of fibrinolysis by streptokinase or Brinase is suggested, because it increases the activity of the cellular immune mechanism. The results to date of an ongoing controlled randomized trial of streptokinase with surgery of tumors of the large bowel are presented, showing that the trends are in favor of streptokinase therapy; however, insufficient time has elapsed to make it, as yet, statistically significant. The action of streptokinase-induced plasmin and Brinase on lymphocytes is described.
Cancer 1975 Jan
PMID:Adjuvant therapy of cancer via the cellular immune mechanism or fibrin by induced fibrinolysis and oral anticoagulants. 117 18

Tumor emboli were produced in lungs of Sprague-Dawley rats by i.v. injection of Walker 256 tumor cells into the tail vein. Tissues were examined by electron microscopy at periods from 30 sec to 72 hr after tumor injection. Two methods of conventional staining were used, in addition to immunoperoxidase techniques, with antifibrin antibodies produced in rabbits. Tumor cells accompanied by a platelet mass were seen in pulmonary arterioles at the earliest time period (30 sec). By conventional staining, small amounts of fibrin were detected within the platelet clumps by 5 min after inoculation. Periodicity indicating stable fibrin was not seen by this technique until 15 to 45 min. When peroxidase-labeled antibody was applied to tissue, sections showed fibrin-positive material at 30 sec, and periodicity of fibrin was detected by 5 min. Fibrin reached a maximum by both techniques at about 1 hr and disappeared, along with the platelets, at about 9 hr. When fibrinolysin was injected prior to the tumor cell inoculation, platelets and fibrin were either absent or present only in traces, and no stable fibrin was detected. These observations show that fibrin occurs very early in small amounts in association with tumor cell emboli, and is removed while the cells are still intravascular.
Cancer Res 1976 Jun
PMID:Demonstration of fibrin in early stages of experimental metastases. 126 44

In order to visualize the receptor for plasmin and plasminogen present on human carcinoma cells, SW1116 and MCF7-MF cells were incubated with biotinylated plasminogen or plasmin and fluoresceinated streptavidin, and counterstained with propidium iodide. It was first demonstrated that biotinylation did not alter the binding properties of plasminogen and plasmin, provided that the biotinylation rate was around 2. Specific staining of tumor cells was obtained using these reagents. Images with green fluorescence were clearly visible as grains or contours at the surface of tumor cells. The localization of fluorescent grains was analyzed more precisely using confocal microscopy. The percentage of stained cells varied from one experiment to another between 10 and 60%. In no experiment were all the cells observed to be positive. Mitotic cells were more frequently stained than non-mitotic cells, suggesting a relationship between the presence of plasmin receptors and cell proliferation. This was confirmed by the use of Ki67 monoclonal antibody (MAb), as B-Pg-binding tumor cells generally had their nucleus stained by this antibody. Other images indicated staining of the extracellular matrix. Finally, 2 rat tumor-cell sub-lines of colonic origin (DHD K12 Pro-b and Reg-b) were shown to bind human biotinylated plasminogen, confirming the strong interspecies reactivity of plasmin receptors.
Int J Cancer 1992 Mar 12
PMID:Visualization of the plasmin receptor on carcinoma cells. 131 64

Cells from rat carcinoma cell lines PROb (giving progressive tumours) and REGb (giving regressive tumours) have cell surface receptors which bind specifically rat plasminogen and plasmin. Affinity for Pg was found to be higher in PROb (Kd = 10(-7) M) than in REGb cells (Kd = 5.10(-7) M) but with a concomitant decrease in the number of binding sites, 0.9 x 10(6)/cell (range from 0.6 to 1.2 x 10(6)) in PROb vs 3.6 x 10(6)/cell (range 1.2 to 6 x 10(6)) in REGb cells. The number and the affinity of binding sites varied in an opposite way in PROb and REGb cells. The difference in affinity parameters was unrelated to the degree of invasiveness of tumour cells in syngenetic rats. Bound plasmin retained its enzymatic activity, which indicates that its binding does not involve the catalytic active site. In cell solubilisates plasminogen receptor appeared as one major band situated in the area of 50-60 kDa.
Br J Cancer 1992 Jul
PMID:Plasminogen receptors on rat colon carcinoma cells. 132 56

We have screened six human squamous carcinoma cell lines for their ability to invade connective tissue by using the experimentally modified chorioallantoic membrane of a chick embryo as an in vivo model of invasion. In confirmation of our earlier studies, all the invasive cell lines expressed high levels of surface-bound urokinase type plasminogen activator (uPA). However, some cell lines expressing this activity were not invasive, suggesting that surface uPA, although necessary, was not sufficient. Since in addition to fibronectin, that can be degraded by uPA or plasmin, chorioallantoic membrane connective tissue contains collagen, we examined the profile of collagenases secreted by the various cell lines in search for an activity that would coincide with the invasive phenotype. We found, using gelatin substrate gels, that type IV gelatinase was produced by all six cell types tested, three cell types produced the M(r) 92,000 gelatinase, and three a lower-molecular-weight activity, which we identified by immunoprecipitation with specific antibodies, and by a direct assay of activity, as interstitial collagenase. Only the latter cells were found to be highly invasive. We showed previously that continuous culture in vitro of one of the carcinoma cell lines, HEp3, led to a gradual extinction of their malignant phenotype. To confirm the correlation between invasion and the production of interstitial collagenase, we examined these two functions in cells freshly isolated from a HEp3 tumor and intermittently during passage in vitro. We found that, although the surface uPA activity was slightly diminished in the in vitro grown cultures, it was still within the range of values found in highly malignant cells, suggesting that it is not the reason for the decrease in invasiveness. In contrast, the reduction in interstitial collagenase closely followed the loss of the invasive phenotype; after 30 in vitro passages the cells were almost completely devoid of interstitial collagenase and unable to invade. The decrease in collagenase activity was not the result of an increased tissue inhibitor of metalloproteinases production.
Cancer Res 1992 Dec 15
PMID:Invasion of connective tissue by human carcinoma cell lines: requirement for urokinase, urokinase receptor, and interstitial collagenase. 133 82

Normal rabbit serum contained two kinds of growth-inhibitory protein, GI-I and GI-II, in latent forms. These latent inhibitors were activated by incubation at 37 degrees C for 12 h, and their activation was lowered by inhibitors for serine, cysteine and metalloproteinases. Both growth inhibitors were highly purified in active forms by successive column chromatographies. GI-I showed a major protein band with an Mr of 18,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while GI-II showed a major protein band with an Mr of 36,000. GI-I and GI-II half-inhibited the growth of rat tumorigenic cell line (RSV-BRL) at concentrations of 0.5 ng/ml and 10 ng/ml, excess concentrations. Of the 15 cell lines tested, GI-I specifically inhibited the growth of rodent and lagomorph cells, whereas GI-II nonspecifically inhibited the growth of all cell lines tested. Specificities for cell type and malignancy were not observed with either inhibitor. These growth inhibitors were stable to a reducing reagent and proteinase inhibitors, but labile to urea, acid, organic solvents, trypsin, plasmin and heating at 95 degrees C for 5 min. These properties suggested that both growth inhibitors might be distinct from known growth-inhibitory factors.
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PMID:Purification and partial characterization of two types of growth-inhibitory protein latently present in rabbit serum. 137 Oct 74

The breakdown of blood clots requires the fibrinolytic action of the serine proteinase plasmin, a two-chain polypeptide derived posttranslationally from its precursor zymogen, plasminogen. While investigating plasminogen gene expression in human extrahepatic tissues, a cDNA sequence was obtained which closely resembled the plasminogen cDNA, yet appeared to represent a distinct gene product. This sequence, which represents the transcript of the recently characterized plasminogen-related gene B, encodes a putative polypeptide of Mr 8800 and is expressed most prominently in malignant cancer cells.
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PMID:A plasminogen-related gene is expressed in cancer cells. 137

Kallikrein activity in human stomach tissue was measured and found to be about threefold higher in cancer tissue than in normal tissue. To clarify the physiological role of this tissue kallikrein, we investigated its effects on the spontaneous metastasis and tumor growth of Lewis tumors (3LL). Antiprotease, aprotinin, and gabexate mesilate (FOY) inhibited spontaneous metastasis but did not inhibit tumor growth, while tissue kallikrein and plasmin enhanced the spontaneous metastasis of 3LL. The results suggest that the inhibitory effects of aprotinin and FOY on metastasis are not only due to an inhibition of tumor cells released by tissue kallikrein, but that tissue kallikrein, a protease, also participates in metastasis. We thus conclude that aprotinin or FOY should be administered either before or immediately after operation to inhibit spontaneous metastasis.
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PMID:Effect of aprotinin on metastasis of Lewis lung tumor in mice. 138 25

Proteinase species secreted by 10 human gastric carcinoma cell lines were analyzed by gelatin zymography and immunoblotting. These cell lines were classified into the following three groups with respect to proteinase secretion: cell lines secreting mainly gelatinases A and/or B; those secreting multiple types of serine proteinases; and those scarcely secreting these enzymes. Two cell lines of the second group, STKM-1 and MKN28, hardly secreted metalloproteinases but secreted the following four types of serine proteinases: (a) two trypsin-like enzymes (M(r) 26,000 and 24,000 in proenzyme forms); (b) a tissue kallikrein-like enzyme (M(r) 150,000 in a complex form); (c) a plasmin-like enzyme (M(r) 70,000); and (d) a plasminogen activator (urokinase-type, M(r) 57,000, from STKM-1 and tissue-type, M(r) 70,000, from MKN28). The M(r) 70,000 plasmin-like enzyme was also detected at lower levels in the conditioned media of four other cell lines (MKN1, MKN45, NUGC-3, and KATO III). The M(r) 24,000 proenzyme of the trypsin-like enzyme was purified from the serum-free conditioned medium of STKM-1. The proenzyme was activated by enterokinase treatment or autolytically by incubation at neutral pH, decreasing its apparent molecular weight from 24,000 to 23,000 on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The activated enzyme extensively degraded fibronectin, laminin, and gelatins and to lesser extents type I, III, IV, and V collagens at 30 degrees C. These results suggest that the matrix serine proteinases may play a major role in the matrix degradation by some kinds of human cancer cells.
Cancer Res 1992 Sep 15
PMID:Multiple secretion of matrix serine proteinases by human gastric carcinoma cell lines. 138 87

To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: determination of prothrombin fragment 1 + 2 and other markers. 138 63


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