Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen of 14 tumor cells or tumor cell lines of guinea pig, mouse, and human origin spontaneously shed procoagulant activity in short-term (4 or 14 to 22 hr) tissue culture under conditions of high cell viability. This released procoagulant activity was pelletable in the ultracentrifuge and was associated with plasma membrane-derived vesicles as determined by transmission electron microscopy and marker enzyme analysis. The procoagulant activity shed corresponded to a substantial fraction of that expressed by intact or sonicated tumor cells and was composed of activities interacting at more than a single step in the clotting sequence. One procoagulant activity associated with shed human tumor vesicles behaved as tissue factor, requiring Factor VII for activity and being inhibited by a specific anti-bovine tissue factor antibody. Guinea pig tumor vesicles also exhibited tissue factor-like activity in a two-stage assay using homologous first-stage Factor VII/X concentrate. None of the human vesicles tested expressed a direct Factor X cleaving activity, independent of Factor VII. Shed tumor vesicles also acted at a second step late in the clotting cascade at the level of prothrombinase generation, presumably by providing a phospholipid surface. Taken together, these data indicate that a wide variety of tumor cells release plasma membrane vesicles with procoagulant activity. Such vesicles, as well as intact tumor cells themselves, may play an important role in the biology of tumor growth by inducing the local fibrin deposits found in association with many solid tumors.
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PMID:Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells. 634 72

Cancer cells may promote fibrin formation in the tumor microenvironment through availability of procoagulant activities which are mainly of two types: tissue thromboplastin-like or direct activator of coagulation factor X. The pharmacological modulation of these activities could be potentially important in the control of metastasis growth. However, very limited information is available so far on this issue; it has recently been shown that the direct activator of coagulation factor X is a vitamin K-dependent activity which is depressed by warfarin treatment, not by anticoagulation with heparin or defibrinating enzymes. Whether the inhibition of this peculiar cancer procoagulant is involved in the antimetastatic activity of warfarin is a stimulating hypothesis which needs to be further substantiated.
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PMID:Cancer cell procoagulants and their pharmacological modulation. 639 43

The association of an acquired inhibitor to factor IX and adenocarcinoma of the sigmoid colon is reported here for the first time. Unlike the lupus anticoagulant, the inhibitor identified did not exhibit marked prolongation of the clotting time using a highly diluted thromboplastin nor was the kinetic behavior of the inhibitor-factor IX interaction time-dependent. Administration of prednisone was associated with the return of the activated partial thromboplastin time to normal values, at which time the tumor was excised and corticosteroids discontinued with no evidence of subsequent factor IX inhibitor activity.
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PMID:Acquired factor IX inhibitor in a patient with adenocarcinoma of the colon. 641 26

The selective antimetastatic agents p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and (+/-)1,2-di(3,5-dioxopiperazin-1-yl)propane (ICRF-159) have been shown to markedly depress the formation of spontaneous hematogenous metastases in mice bearing s.c. Lewis lung carcinoma, with a mechanism unrelated to cytotoxicity for tumor cells. The effects on hemostasis of DM-COOK, DTIC and ICRF-159 have thus been examined in comparison with those of a purely cytotoxic agent, cyclophosphamide, in mice bearing i.m. Lewis lung carcinoma. The parameters considered are the number of platelets and their aggregability, prothrombin and partial thromboplastin times, plasma fibrinogen concentration and tumor cell procoagulant activity. Slight variations are caused by drug treatment in tumor-bearing mice as compared with untreated tumor-bearing controls; the pattern of effects of the selective antimetastatic agents does not differ from that of the reference cytotoxic compound used, cyclophosphamide. These data thus indicate that the effects on hemostasis of the drugs examined can contribute only marginally to their antimetastatic action, since more pronounced effects on hemostasis have been shown to be required to significantly affect metastasis formation.
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PMID:Hemostasis and mechanism of action of selective antimetastatic drugs in mice bearing Lewis lung carcinoma. 654 Jan 95

Disseminated intravascular coagulation (DIC) was diagnosed as a secondary disease in 6 horses. Four horses had localized and/or systemic sepsis, one horse had disseminated neoplasia, and one had idiopathic ulcerative enteropathy. The diagnosis of DIC was based on the finding of at least 3 of 4 abnormalities: thrombocytopenia, prolonged prothrombin time, prolonged activated partial thromboplastin time, and a high concentration of fibrinolytic degradation products. The most common clinical signs other than those attributable to the primary disease process were abnormal hemorrhage (4 hours) and venous thrombosis (4 horses). All horses eventually died or were euthanatized because of the severity of the primary disease.
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PMID:Disseminated intravascular coagulation in six horses. 664 11

The plasma values for factors (F)VII, FVIII:C, FVIIIR:Ag, FIX, FX, and FXI and the thrombin clotting time (TCT) were determined for 28 dogs with naturally occurring hepatic disease. The major morphologic type of hepatic disease present in a given dog, as determined by hepatic biopsy and histopathologic examination, was degeneration (12 dogs), inflammation (9 dogs), cirrhosis (3 dogs), or neoplasia (4 dogs). A specific morphologic diagnosis also was made for each dog in the study. Plasma coagulation factor values and screening tests were consistently abnormal in greater than 50% of the dogs with each type of hepatic disease as follows: degeneration--decreased FXI; inflammation--increased FVIIIR:Ag; cirrhosis--shortened TCT, decreased FIX, FX, and FXI, and increased FVIIIR:Ag; and neoplasia--shortened TCT, decreased FVIII:C, and increased FVIIIR:Ag. The plasma coagulation factor values were compared with serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, fibrinogen-fibrin degradation product (FDP) concentration, and the prothrombin time (PT) and activated partial thromboplastin time (APTT) to determine the sensitivity and specificity of each test in detection of hepatic disease. Of all dogs with hepatic disease, 93% had at least 1 abnormal coagulation test value. The PT and APTT were abnormal in 50% and 75%, respectively, of these same dogs. Increased serum ALT and ALP activities were present in 61% and 50%, respectively, and FDP concentrations were increased in 14% of dogs with hepatic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma coagulation factor abnormalities in dogs with naturally occurring hepatic disease. 666 Jun 23

14C-Labeled single-chain factor X prepared by vitamin K-dependent carboxylation in vitro was partially purified by adsorption to BaSO4 and chromatography on DEAE-Sephacel. Known activators of factor X were analyzed for their effect on the single-chain molecule. 14C-Labeled factor X antigens were recovered immunochemically from incubation mixtures and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Incubation with trypsin resulted in the generation of factor Xa clotting activity, and the 14C-labeled product migrated after reduction with an apparent molecular weight of 22,500 +/- 1500 (mean +/- 1 SD). The light chain produced by factor Xa was similar to that produced by trypsin (Mr 24,500 +/- 1500; mean +/- 1 SD). Incubation of single-chain factor X with factor VII and thromboplastin, factor IXa, or the factor X activating enzyme from Russell's viper venom gave a reducible product with a light chain of higher apparent molecular weight (Mr 37,000-38,000). Incubation with factor VII and thromboplastin also resulted in the generation of factor Xa clotting activity. Incubation of single-chain factor X with platelets resulted in the binding of about 20% of the 14C. The bound 14C-labeled factor X antigen released by freezing and thawing in the presence of EDTA was reduced to give a 14C-labeled polypeptide with Mr 31,000. Walker 256 tumor cells bound about 30% of the 14C. The bound material, after reduction, gave a 14C-labeled polypeptide with Mr 23,000.
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PMID:Functional characterization of single-chain factor X from rat liver. 671 51

Thromboplastic and fibrinolytic activities of 8 lines of cultured human gastric cancer cells were estimated both in cell lysate and serum-free supernatant fraction. Furthermore, cell lysates with differing levels of thromboplastic activity were injected intravenously into congenitally athymic nude mice and the role of this activity in thrombus formation was examined. Thromboplastic and fibrinolytic activities of the cell lysate and the serum free-supernatant fraction varied from one line to another. There was no apparent correlation between these activities and the degree of histological differentiation of the original tumor. The thromboplastic activity was factor VII-dependent and factor IX-independent, indicating that it was attributable to tissue thromboplastin, although some factor VII-independent thromboplastic activity was also included in the cell lysate of two lines. Intravenous injection of the cell lysate with high thromboplastic activity produced more thrombi in the lung than that with low thromboplastic activity. This suggests that thromboplastic activity of cancer cells might play a significant role in the development of the hypercoagulable state in patients with gastric cancer.
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PMID:Thromboplastic and fibrinolytic activities of cultured human gastric cancer cell lines. 686 45

Human umbilical vein endothelial cells in culture synthesize thromboplastin upon stimulation with phytohaemagglutinin (PHA) or the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The thromboplastin activity is further strongly enhanced in a time dependent reaction by the presence of gel-filtered platelets or platelet aggregates. This effect was demonstrable at platelet concentrations lower than those normally found in plasma, it may thus be of pathophysiological relevance. The thromboplastin activity increased with increasing number of platelets added. Cycloheximide inhibited the increase, suggesting that de novo synthesis of the protein component of thromboplastin, apoprotein III, is necessary. When care was taken to remove monocytes no thromboplastin activity and no apoprotein III antigen could be demonstrated in suspensions of gel-filtered platelets, platelets aggregated with thrombin or homogenized platelets when studied with a coagulation assay and an antibody neutralization technique.
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PMID:Platelets stimulate thromboplastin synthesis in human endothelial cells. 686 14

Conventional laboratory methods were used to screen untreated tumor-bearing dogs for hemostatic abnormalities. Excluded from study were dogs with clinical evidence of bleeding. The primary site for neoplastic disease in 100 dogs studied included hemolymphatic system, skin, bone, thyroid gland, oropharynx, mammary gland, and nasal cavity. Eighty-three percent of the dogs had one or more abnormal coagulation tests. Thrombocytopenia occurred in 36 dogs and 3 had thrombocytosis. Twenty-five dogs had hypofibrinogenemia, and 25 had hyperfibrinogenemia. There were 32 dogs with prolongation of the activated partial thromboplastin time, 10 dogs with shortened prothrombin time, and 6 dogs with prolongation of the thrombin time. Sixteen dogs had positive protamine sulfate (paracoagulation) reaction, and 8% had increased plasma fibrin degradation products. The euglobulin lysis time was accelerated in 24% of the dogs, and 15% had schistocytes on blood film. These data indicate that the majority of dogs with advanced neoplasms are likely to have abnormal coagulation tests.
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PMID:Coagulation abnormalities in dogs with neoplastic disease. 689 2


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