Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to purify and characterize the agent responsible for the antimetastatic activity of an extract of the salivary glands (SGE) of the Mexican leech Haementeria officinalis. When administered intravenously in mice on the same day as the intravenous inoculation of T241 sarcoma cells, SGE markedly reduces the number and size of lung tumor colonies. In designing a purification protocol for the antimetastatic agent, we postulated that the antimetastatic agent would also display anticoagulant activity. Thus, we discovered that heparin affinity chromatography followed by anion-exchange chromatography results in a fraction highly enriched in both potent anticoagulant activity and potent antimetastatic activity. Approximately, 200-300 micrograms of purified protein is isolated from 150 mg of SGE. As little as 15 micrograms of this material inhibits tumor cell metastasis to the same extent as 1.0 mg of the unfractionated SGE. When analyzed on sodium dodecyl sulfate gels the active fraction consists mainly of one polypeptide band having an apparent molecular weight of approximately 17,000 under either reducing or nonreducing conditions. The protein has a pI of approximately 9.5 and a molecular weight of approximately 17,000 under nondenaturing conditions. A specific antiserum prepared against the 17,000-dalton protein indicated that this protein is the major anticoagulant and antimetastatic agent of leech salivary gland extract. We have termed this anticoagulant, antimetastatic agent "antistasin." We hypothesize that antistatin inhibits coagulation via factor Xa, and not thrombin, since factor Xa, but not thrombin, is rapidly inactivated upon addition of antistasin. The mechanism of antistasin's antimetastatic activity is currently under investigation.
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PMID:Isolation and characterization of antistasin. An inhibitor of metastasis and coagulation. 368 95

Acquired inhibitors of coagulation cause a life-threatening disease. Clinically newly occurring hemorrhagic diathesis combined with prolonged activated partial thromboplastin time (aPTT) time is diagnostically indicative and can be confirmed by a positive plasma exchange test. For thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP-HUS) the diagnosis of Coombs negative hemolytic anemia together with thrombocytopenia should lead to the detection of fragmentocytes in peripheral blood smears. Hairy cell leukemia is a rare subgroup of chronic B-cell neoplasia with the clinical signs of pancytopenia and splenomegaly which characteristically stain positive for CD103. The gastrointestinal stromal tumor (GIST) has nothing in common with classical soft tissue sarcoma based on the activating mutation of the KIT or PDGFRA gene (positivity for CD117). In all of these disorders the correct diagnosis has a major influence on patient outcome. For the case of acquired inhibitors of coagulation immunosuppressive therapy and substitution of coagulation factors (e.g. recombinant factor VIIa) or for TTP-HUS the immediate start of plasma exchange are mandatory. For hairy cell leukemia a very effective treatment exists with purine analogs (e.g. cladribine) and for metastatic inoperable GIST with tyrosine kinase inhibitors (e.g. imatinib).
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PMID:[Hemato-oncological diseases]. 2398 1