Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large body of experimental evidence suggests that plasminogen activators provide tumoral cells with efficient means to degrade extracellular matrix constituents and thereby facilitate their dissemination to distant sites. Melanocytic neoplasia encompass a spectrum of lesions exhibiting diverse clinical behavior that remain difficult to predict with current histopathological evaluations. Little information concerning the contribution of plasminogen activation in diagnostic specimens of human melanocytic tumors is presently available. We thus analyzed biopsy specimens of pigmented skin lesions by histological techniques that identify the cellular sites of synthesis of plasminogen activators and of their inhibitors and that localize the sites of plasminogen activators-catalyzed enzymatic activities. We found that urokinase-type plasminogen activators (uPA) and plasminogen activator inhibitor type 1 mRNAs accumulate in atypical nevocytes and in melanoma cells, but not in benign nevocytes. However, uPA-catalyzed proteolytic activity was detected exclusively in melanomas. These observations suggest that up-regulation of the uPA gene is an early feature of melanocyte transformation and that unbalanced enzyme/inhibitor activity is associated with the malignant phenotype. By supporting a role for uPA in melanoma invasiveness, they provide a novel tool for the evaluation of atypia in nevi.
 ...
PMID:Plasminogen activation in melanocytic neoplasia. 804 5

The interaction of thrombin with plasminogen activator inhibitor 1 (PAI-1) is shown to result in the simultaneous formation of both cleaved PAI-1 and a sodium dodecyl sulfate-stable thrombin-PAI-1 complex. The kinetics of this reaction can be described by a "suicide substrate" mechanism that includes a branched reaction pathway, which terminates in either the stable inhibitor-enzyme complex or the cleaved inhibitor plus free enzyme. Because of the branched pathway, approximately three moles of PAI-1 are needed to completely inhibit one mole of thrombin. Heparin and vitronectin enhance the rate of inhibition from 9.8 x 10(2) L mol(-1) s(-1) to 6.2 x 10(4) L mol(-1) s(-1) and 2.1 x 10(5) L mol(-1) s(-1), respectively, under optimal conditions. In addition to enhancing the rate of inhibition, both cofactors increase the apparent stoichiometry of the PAI-1-thrombin interaction, with cofactor concentration dependencies similar to the inhibition reaction. Thus, at 37 degrees C approximately six cleavage reactions occur per inhibition reaction. Therefore, thrombin will efficiently inactivate PAI-1 in the presence of either vitronectin or heparin, unless a sufficient excess of the inhibitor is present. These results show that physiological cofactors are able to switch a protease-serpin inhibition reaction to a substrate reaction, depending on the local concentrations of each of the components.
 ...
PMID:The suicide substrate reaction between plasminogen activator inhibitor 1 and thrombin is regulated by the cofactors vitronectin and heparin. 929 20

Skin melanoma is believed to result from malignization of an inborn or acquired pigmented nevus under the action of a number of causative agents. With regard to this, the comparative analysis of skin melanoma tissue samples taken from patients of both sexes and pigmented nevus tissue samples was performed by polarization fluoroimmunoassay. The study involved analyzing the activity of plasmin, plasminogen, concentration and activity of urokinase type plasminogen activator, tissue type plasminogen activator, plasminogen activator inhibitor, as well as the level of growth factors--vasculoendothelial one and its receptor, epidermal one and its receptor, transforming one, fibroblasts growth factor, insulin-like 1 and 2 growth factors. The detected changes indicate possible mechanisms of malignant transformation of skin nevi. The obtained results can be used for developing the risk evaluation methods for neoplastic transformation of nevi as well as prevention methods.
 ...
PMID:[Indicators of plasminogen activation system and growth factors in the tissue of nevi and skin melanoma]. 2583 1