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)

Cancer procoagulant A (CPA) was originally described in extracts of tumor tissue, but whether this represented a quantitative and/or a qualitative difference from procoagulant activity in normal tissue extracts was not clear. Procoagulant activity was quantitated in extracts of 12 matched normal and malignant human tissue samples from the large intestine, breast, lung, and kidney. The specific activity of procoagulants in the tumor extracts was not greater than that in the extracts of normal tissue. Two enzymatic characteristics of CPA that distinguish it from tissue thromboplastin are its inhibition by diisopropylfluorophosphate (DFP) and its lack of dependence on factor VII. These specific tests were used to evaluate qualitative differences between procoagulants from normal and malignant intestinal tissues. In the paired normal and malignant tissue extracts, all tumor samples were inhibited by DFP and were active in factor VII-depleted bovine plasma (F7D-BP). In contrast, the extracts of normal tissue were insensitive to DFP and, except for one extract, were inactive in F7D-BP. Four of 9 other tumor extracts (44%) were positive for both of these tests for CPA, whereas the other 5 extracts were positive for only one of the two tests. The results suggest that extracts of normal and malignant tissues contained similar levels of procoagulant. However, malignant tissue contained a procoagulant enzymatically different from normal tissue thromboplastin. Furthermore, most of the malignant tissue extracts seemed to contain little or no thromboplastin.
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PMID:Comparison of procoagulant activities in extracts of normal and malignant human tissue. 28 92

The protease, cancer procoagulant, was isolated from three murine metastatic tumors and was purified to apparent homogeneity (SDS-PAGE) from Lewis lung cells by the sequence of (NH4)2SO4 precipitation, DE-53 anion-exchange chromatography, and Sephacryl 200 chromatography. The murine tumor enzyme has a molecular weight of 68,000 and Ca2+ is required for procoagulant and proteolytic activity; thus, the murine enzyme is very similar to that isolated from rabbit tumors. Two peptidyl chromogenic substrates of cancer procoagulant were discovered, facilitating kinetic and inhibition studies with the enzyme. The peptide substrate structures and the results of inhibition studies suggest that cancer procoagulant is thrombin-like in specificity but is a thiol protease.
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PMID:The purification and properties of cancer procoagulant from murine tumors. 157 50

We studied several blood coagulation parameters and tumor tissue procoagulant activity (PCA) in nude mice bearing human colorectal carcinomas (HCC). In a control group of 51 tumor-free nude mice, platelet number was 1.2 +/- 0.03 x 10(6)/microliters, thrombotest activity 90% +/- 2.6 and fibrinogen 172 +/- 11 mg/dl. The same parameters were studied in nude mice (n = 71) bearing 7 different HCC lines subcutaneously (s.c.). The results did not significantly differ from those in control mice but there was broad variability among groups of mice injected with different HCC lines, ranging from 0.36 to 2.55 x 10(6)/microliters for platelets, from 100 to 28% for thrombotest activity and from 42 to 460 mg/dl for fibrinogen. The results were significantly (p less than 0.05) different from those in the tumor-free group when each group of HCC-bearing animals was analyzed individually. A malignant HCC line that grew in the liver of nude mice (n = 24) significantly (p less than 0.001) reduced thrombotest activity (58% +/- 5.9). The PCA of tissue extracts from tumors grown s.c. in nude mice was assayed. All the HCC xenografts expressed PCA which differed significantly for the various tumor lines (from 25.5 +/- 1.9 to 2.8 +/- 0.6 unit/mg in tumor tissue). Cancer procoagulant (CP), a cysteine proteinase with a direct factor-X-activating effect, was present in different amounts (84.7 +/- 4.3 to 59.5 +/- 9.0%) in the tumors. Our results indicates that the nude mouse is a suitable model for evaluating the hemostatic changes induced by human tumors and may represent a tool for investigating the underlying biochemical mechanisms.
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PMID:Blood coagulation changes in nude mice bearing human colon carcinomas. 172 16

The paraneoplastic syndrome (PNS) is an association of symptoms and signs not directly related to the site or local manifestations of a malignant tumor or its metastases. Hematologic abnormalities as PNS include erythrocytosis, anemia, neutrophilia, neutropenia, eosinophilia, thrombocytosis, thrombocytopenia, venous thromboembolism and disseminated intravascular coagulation (DIC). These abnormalities are, by and large, due to the production of biologically active growth factors, hormones or as yet unidentified "humors" by the tumor. As our understanding of growth factors controlling hematopoiesis has increased in recent years, the biologic basis of hematologic PNS are better understood. For instance, tumor-associated neutrophilia is now known to be caused by the production of G-CSF by the tumor. The mechanism by which tumor causes thromboembolism have also been extensively investigated. Cancer cells induce platelet aggregation both in vitro and in vivo. Platelet aggregating material has been isolated and partially characterized from tumor cells. The involvement of platelet glycoprotein II b/IIIa in the tumor-platelet interaction has also been shown. Malignant cells contain a unique procoagulant, cancer procoagulant A, that directly activates factor X. Together with tissue factor, this procoagulant appears to have been contribute to a high incidence of thromboembolism in cancer patients. Better understanding of hematologic PNS is important for clinical care of the patients with cancer.
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PMID:[Paraneoplastic syndrome hematologic abnormalities]. 200 36

Cancer procoagulant (CP) is a Mr 68,000 cysteine proteinase that initiates blood coagulation and is expressed by a variety of malignant cells but not by normally differentiated cells. Polyclonal immunoglobulin G and monoclonal immunoglobulin M antibodies were developed to purified CP and used to develop an enzyme-linked immunosorbent assay to analyze the antigen in human serum samples. The purpose of this preliminary study was to determine whether or not the analysis of CP in the serum might be a useful tumor marker. Pure CP was added to normal serum to establish a quantitative standard curve; the correlation coefficient of seven standard curves was 0.99. The upper limit of the normal range was established with 46 normal sera (mean +/- 2 SD = 0.57 microgram/ml). A total of 128 blinded serum samples were analyzed: 54 were from cancer patients (29 with gastrointestinal cancer, 22 with lung cancer, and three with urogenital cancer); 20 were from benign disease patients; and 54 were from normal individuals. All of the 13 early stage cancers were greater than 0.57 microgram/ml (positive), 31 of 41 (76%) of the late stage cancers were positive; overall, 44 of the 54 cancers (81%) were positive. Forty-nine of 54 (91%) of the normal sera and 16 of 20 (80%) of the benign disease sera were negative. Overall, the assay had a sensitivity of 81% and a specificity of 88%.
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PMID:An enzyme-linked immunosorbent assay for cancer procoagulant and its potential as a new tumor marker. 216 40

Rabbit V2 carcinoma tissue is the tumor in which cancer procoagulant activity (CP) was first described, purified and identified as a cysteine proteinase able to activate F X directly. In the present study we show that CP of V2 carcinoma extracts is depressed in its biological activity (although the antigen is present) by warfarin treatment. The biochemical basis for this effect is offered by the identification of Vit.K-dependent gamma-carboxylase in the microsomal fraction of the tumor tissue. V2 carcinoma tissue had very low endogenous substrate(s) of tumor carboxylase in basal conditions but this increased threefold after warfarin. The accumulation of endogenous substrate(s) and the depression of the CP activity by warfarin raises the possibility that CP represents at least one of the substrates for gamma-glutamyl carboxylase in this experimental tumor tissue.
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PMID:Evidence of a warfarin-sensitive cancer procoagulant in V2 carcinoma. 250 Nov 68

Elevated activities of cysteine proteinases such as cathepsins B and L and cancer procoagulant have been linked to tumor malignancy. In the present study we examined the hypothesis that these elevated activities could be due to impaired regulation by the endogenous low molecular mass cysteine proteinase inhibitors (cystatins). Inhibitors from human sarcoma were compared to those from human liver, a normal tissue in which the inhibitors had been characterized previously. An extract of cystatins from sarcoma was less effective against papain and cathepsin B (liver or tumor) than was an extract from liver. This reduced inhibitory capacity in sarcoma was not due to a reduction in either the concentrations or specific activities of the cystatins or an absence of any family or isoform of cystatins. We purified two members of the cystatin superfamily (stefin A and stefin B) to homogeneity and determined their individual inhibitory properties. Stefins B from liver and sarcoma exhibited comparable inhibition of papain and cathepsin B. In contrast, stefin A from sarcoma exhibited a reduced ability to inhibit papain, human liver cathepsins B, H and L and human and murine tumor cathepsin B. The Ki for inhibition of liver cathepsin B by sarcoma stefin A was 10-fold higher than that for inhibition of liver cathepsin B by liver stefin A, reflecting a reduction in the rate constant for association and an increase in the rate constant for dissociation. Cancer is now the third pathologic condition reported to be associated with alterations in cystatins, the other two being amyloidosis and muscular dystrophy.
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PMID:Inhibitory properties of low molecular mass cysteine proteinase inhibitors from human sarcoma. 280 24

This study was originally designed to investigate whether there is any correlation between the type of procoagulant activity (PCA) and the tumorigenicity of transformed cells. The data obtained are relevant to this question and to defining the differences in the expression of cellular activities depending on the in vitro system used. PCA was measured and characterized in normal, immortalized, and tumorigenic mouse fibroblasts. In all the cell lines studied the activity was of tissue factor type, as established with functional, enzymatic, and immunochemical criteria. However, the PCA of cells freshly isolated from the tumors induced by tumorigenic cell lines was of cancer procoagulant type, i.e. a cysteine protease with direct factor X activator activity. The same cells, when cultured in vitro, expressed again PCA of tissue-factor type. These results suggest that either a tumor-host interaction is required for the expression of cancer procoagulant or the latter activity, produced by tumor cells under in vitro conditions, is destroyed or inactivated during the culture period. Our findings caution against defining the procoagulant activity of tumors based on experiments on cultured cells.
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PMID:Procoagulant activity of mouse transformed cells: different expression in freshly isolated or cultured cells. 320 84

Cancer Procoagulant (CP), a cysteine proteinase which triggers blood coagulation by directly activating Factor X (FX) in the absence of Factor VII (F VII), has recently been isolated from rabbit V2 carcinoma and biochemically characterized. We have studied the procoagulant activity of tissue extracts from 4 murine experimental tumors in order to define whether or not a F VII-independent activity with cysteine proteinase characteristics was present. The tumors studied were: Lewis lung carcinoma (3LL), B16 melanoma (B16), JW sarcoma (JWS) and the M4 variant of the mFS6 fibrosarcoma (M4). Extracts from 3LL, B16 and JWS tumor initiated coagulation in both the presence and absence of F VII, their procoagulant activity was sensitive to iodoacetamide (1 mM) and mercury chloride (0.1 mM). The procoagulant of M4 extract was dependent on the presence of F VII and was not significantly affected by the cysteine proteinase inhibitors. An Ouchterlony double immunodiffusion study showed immunological cross-reactivity of all but M4 extracts to a polyclonal antibody to purified CP. The present study suggests that the procoagulant(s) present in the murine tumors 3LL, B16 and JWS are enzymatically and immunologically indistinguishable from cancer procoagulant of the rabbit V2 carcinoma.
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PMID:Several murine metastasizing tumors possess a cysteine proteinase with cancer procoagulant characteristics. 329 10

Rabbit V2 carcinoma tissues have been described to possess a procoagulant activity with specific characteristics; this material has been purified and identified as a cysteine proteinase able to directly activate coagulation factor X. We have shown here that the procoagulant activity of V2 carcinoma extracts is depressed in warfarin-treated animals, thus suggesting that cancer procoagulant could represent a new vitamin K-dependent protein. The biochemical basis for this effect is offered by the identification of gamma-glutamyl carboxylase in the microsomal fraction of tumor tissues. The V2 carcinoma has a carboxylase activity which is increased in warfarin-treated animals. An endogenous substrate of tumor carboxylase, the nature of which has not been identified, has been found 5-fold increased in warfarin-treated animals. The presence of gamma-glutamyl carboxylase was also described in several murine tumors including both carcinomas and fibrosarcomas. It is worth mentioning that all the tumors tested produce a procoagulant with the peculiar characteristics of that described in V2 carcinoma. It is conceivable that cancer procoagulant could represent at least one of the substrates for gamma-glutamyl carboxylase in these experimental tumor tissues.
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PMID:gamma-Glutamyl carboxylase activity in experimental tumor tissues: a biochemical basis for vitamin K dependence of cancer procoagulant. 353 Sep 4


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