Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of two proteinase inhibitors -- Trasylol (Trascolan "Polfa") and PAMBA ("Germed") -- on experimental metastases of melanotic melanoma has been studied in golden hamsters. Animals were injected intravenously with tumour cells (5x10(5) or 10(6) in 0.2 ml of saline). They obtained protease inhibitor intraperitoneally one hour prior, or one hour after melanoma cells injection. One group of hamsters were also inoculated with tumour cells preincubated 10 min. in saline containing Trasylol or PAMBA. A diminished number of experimental metastases to the lungs in each group has been observed.
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PMID:The effect of trasylol (Trascolan "Polfa") and p-aminomethylbenzoic acid (Pamba "Germed") on the experimental metastases of transplantable melanotic melanoma in golden hamster (Mesocricetus auratus, Waterhouse) 30 92

The production of protease by malignant cells has been held responsible for invasion. The effect of aprotinin, a broad-spectrum protease inhibitor, on malignant invasion was examined histologically in organotypical cocultures of precultured embryonic chick heart fragments with two human melanoma cell lines and one virus-transformed fetal mouse carcass cell line. In the presence of 400 KIU/ml aprotinin, invasion was still permissive, while in the comparison with 0.1 microgram/ml vincristine, a microtubule and directional motility inhibitor and a well-documented anti-invasive agent, invasion was completely stopped. Aprotinin remained stable in the culture medium so that the presence of invasion cannot be explained by low drug concentration. It is concluded that aprotinin-sensitive proteases are not implicated in invasion in vitro in the cell types investigated, and that this in vitro technique deserves further interest for the study of protease inhibitors in the mechanism of invasion.
Clin Exp Metastasis
PMID:The influence of the protease inhibitor aprotinin on tumor invasion of three cell lines in vitro. 244 88

All malignant tumors shed cells into the circulation. The number of circulating tumor cells bears no relation to the extent of secondary growth. This is determined by the number of tumor cells that cross the vessel wall and implant in extravascular sites. The rate of cellular emigration is regulated by the permeability of vessels harbouring tumor emboli, permeability in turn being dependent on the amount of alpha, 2, macro-globulin (AMG) lining vascular endothelium. Agents which inactivate or digest AMG, e.g. proteases, have been shown to promote the dissemination of tumor. Some tumors secrete large amounts of proteases. These enzymes are believed to lyse the AMG layer and so to facilitate the emigration of tumor cells. On this hypothesis, inhibitors of such proteases would have anti-metastatic properties. Present experiments lend support to this view. The proteinase inhibitor Trasylol, when allowed to act on tumor cells, has been shown to impair their capacity of setting up haematogenous metastases. It does not affect their viability or transplantability. It is suggested therefore, that blood-borne tumor dissemination might be inhibited by perfusing the (primary) tumor bed with proteinase inhibitor, possibly in association with AMG.
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PMID:On the prevention of haematogenous tumor metastases rats. The role of the proteinase inhibitor "Trasylol". 616 35

Anti-fibrinolytic agents such as aprotinin and epsilon-aminocaproic acid (EACA) are used clinically to decrease peri-operative bleeding. Use of these treatments during cancer-related surgeries has led to investigation of the effect of fibrinolysis inhibition on cancer cell spread. The ability of aprotinin to reduce proteolytic activity of proteases required for metastasis suggests that it could have an anti-metastatic effect in patients undergoing tumor resection. However, many metastatic cells in the vasculature of a secondary tissue are associated with a micro-thrombus. The association of tumor cells with thrombi has been shown to increase their survival; therefore inhibition of plasmin-mediated fibrinolysis might instead increase metastatic cell survival by enhancing the association between thrombi and tumor cells. The goal of this work was to determine the effect of anti-fibrinolytic treatment on experimental metastasis and to establish the role of coagulation factors in this effect. The metastatic ability of B16F10 melanoma cells was evaluated in vivo following cell or animal pre-treatment with aprotinin or EACA. Additionally, a novel in vivo technique was developed, to permit analysis of tumor cell association with thrombi in the lung microvasculature using confocal microscopy. Aprotinin and EACA treatment of mice resulted in a significant increase in lung metastasis. Aprotinin treatment increased the size of thrombi in association with cells arrested in lung capillaries. This study suggests that clinical use of anti-fibrinolytic agents for cancer-related surgeries could result in increased metastatic ability of those cells shed immediately prior to and during surgery, and that this approach thus requires further study.
Clin Exp Metastasis 2009
PMID:Effect of anti-fibrinolytic therapy on experimental melanoma metastasis. 1908 67

A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus tener tener (Mtt) venom. It showed a molecular mass of 6542Da, similarly to Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin (0.5nM) on synthetic substrate S-2251 was inhibited by 91% following the incubation with TP1 (1nM). Aprotinin (2nM) used as the positive control of inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic activity (0.05nM) was inhibited by 67% following incubation with TP1 (0.1nM). The degradation of fibrinogen chains induced by plasmin, trypsin or elastase was inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains, previously attributed to metallopeptidases, was not abolished by TP1. The tPA-clot lysis assay showed that TP1 (0.2nM) acts like aprotinin (0.4nM) inducing a delay in lysis time and lysis rate which may be associated with the inhibition of plasmin generated from the endogenous plasminogen activation. TP1 is the first serine protease plasmin-like inhibitor isolated from Mtt snake venom which has been characterized in relation to its mechanism of action, formation of a plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a biological characteristic of great interest in the field of biomedical research. They could be used to regulate the fibrinolytic system in pathologies such as metastatic cancer, parasitic infections, hemophilia and other hemorrhagic syndromes, in which an intense fibrinolytic activity is observed.
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PMID:Purification and characterization of tenerplasminin-1, a serine peptidase inhibitor with antiplasmin activity from the coral snake (Micrurus tener tener) venom. 2641 85