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

Acute promyelocytic leukemia (APL) is characterized by proliferation of morphologically abnormal promyelocytes and a severe bleeding diathesis. The abnormal promyelocyte is characterized by abundant, large granules, many of which are spindle-shaped. Electron microscopic appearance of the granules closely resembles that of Auer rods. The granules appear to possess tissue thromboplastin activity by both immunologic and clotting assays. Coagulation studies in APL are generally consistent with disseminated intravascular coagulation. Prolongation of the prothrombin time and elevation of fibrinogen degradation products are the tests that are most commonly abnormal. Although occasional reports indicate a favorable response of the coagulopathy to drugs that inhibit fibrinolysis, the use of prophylactic heparin appears to be the treatment of choice. The response rate of APL to chemotherapy regimens that contain an anthracycline is comparable to that of acute myelogenous leukemia. The recent description of the 15;17 chromosomal translocation which may be pathognomonic for APL is only the second example of a chromosomal marker of human neoplasia. Marked elevation of serum vitamin B12 and B12 binding proteins appears to be another characteristic feature of APL. An in vitro cell line of APL cells has been demonstrated to have the capacity to differentiate to functional polymorphonuclear leukocytes, but the cause for the maturation arrest is unknown.
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PMID:Acute promyelocytic leukemia. 39 71

A comparative study, condicted on the coagulation status, indicated that tumor and chronic inflammatory processes in the lung as associated with high blood content of fibrinogen and fibrinogen B, the increased plasma tolerance to heparin and degree of thrombotest with a compensatory increase of the heparin content and antithrombin activity. Lung tumor patients contrary to patients with pneumonias showed a high thromboplastin activity and reduced fibrinolysis indices. The activation of euglobulin fibrinolysis is characteristic of the hemostasis system in patients with chronic pneumonias. The revealed alterations may be used both for timely prophylaxis of coagulopathy and as an adjuvant method in the differential diagnosis.
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PMID:[Hemostasis system in lung cancer, benign tumors and chronic nonspecific pneumonias]. 43 13

Crude tumor cell extract from rat ascites hepatoma AH130 revealed a high thromboplastic activity. Intravenous injection of the extract caused widespread thrombus formation in the capillaries, arterioles, and arteries of the lung. Intravenous inoculation of AH130 after an injection of the tumor cell extract produced metastatic foci in the larger arteries, compared with the case injected with only AH130 which developed metastatic foci mainly in and around the alveolar septa. These results suggest the role of tumor thromboplastin material in the mode of distribution of metastatic foci in the lung.
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PMID:Role of tumor thromboplastin in the mode of distribution of metastatic foci in the lung. 52 Jul 53

Soon after i.v. injection of ascites hepatoma cells of rat, 3 types of tumour-cell emboli were found in arterioles and capillaries of the lung. The first type had marked aggregation of platelets and deposition of fibrin. Many were seen when tumour cells with high thromboplastic activity (AH 130) were injected, and were often followed by detachment and fragmentation of endothelial cells. The second type had loosely aggregated platelets and the third type had no aggregation of platelets or deposition of fibrin. The latter 2 types were mainly seen when the tumour cells with low thromboplastic activity [AH 130 F(N)] were injected, and they did not accompany severe structural changes of the endothelial cells. Tumour cell-platelet complexes appeared to be induced by tissue thromboplastin released from tumour cells rather than from the endothelial cells. One to 6 h after injection of AH 130, tumour cells were found beneath the endothelial cells detached from the basement membrane in areas with microthrombi. Breaching of the endothelial cells with the processes of tumour cells was also seen then. Intrusion of the processes of tumour cells into the endothelial cells was noted in groups injected with either AH 130 or AH 130 F(N), but not in the junctions of the endothelial cells. Metastatic foci 3 days after the injection of AH 130 were more frequent than in the rats injected with AH 130 F(N). These results indicate that thromboplastic activity of tumour cells might be important in forming microthrombi in the lodgement phase and might be one of the factors facilitating blood-borne metastasis.
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PMID:Lodgement and extravasation of tumour cells in blood-borne metastasis: an electron microscope study. 69 45

An initial clinical phase I trial of inosine dialdehyde has been carried out in 40 patients at dose levels of 30-4000 mg/m2 for 5 days given intravenously (iv) monthly. At 1.5 g/m2, noncumulative dose-related toxicity occurred in all patients which consisted of nausea and vomiting, local pain, alterations in coagulation mechanism, elevated partial thromboplastin time, and positive Coombs' test. No dose-limiting leukopenia, thrombocytopenia, anemia, or bleeding occurred; however, depression of the leukocyte and platelet counts, and decreased hemoglobin value were observed. The dose-limiting toxic effect was renal tubular damage with reversible acute renal failure in one of four patients who received 3000 mg/m2 iv for 5 days. Refractory hypercalcemia was controlled in three of three patients without tumor effect. Responses occurred in patients with seminoma, oat cell carcinoma, and melanoma. A starting dose of 2 g/m2 for 3 days monthly is recommended for phase II trials and a trial in lung carcinoma is now being conducted.
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PMID:Clinical phase I trial of inosine dialdehyde (NSC-118994). 110 41

Human blood monocytes (Mo) and monocyte-derived macrophages (M psi) possess cytotoxic effects against tumor cell lines when appropriately stimulated by various biological response modifiers, e.g., gamma interferon (gamma IFN) and muramyltripeptide (MTP). Activated Mo/M psi represent a new tool for the treatment of human malignancies, termed "adoptive cellular immunotherapy". Activated Mo/M psi express tissue factor procoagulant activity (PCA), which is a physiological trigger of blood coagulation. PCA was evaluated in vitro using a modification of the one-stage recalcification clotting time, and hemostatic changes were studied in vivo in cancer patients. Nine patients with peritoneal carcinomatosis were injected intraperitoneally with activated Mo and 11 patients with non-small cell lung carcinomas were infused intravenously with activated M psi. Hemostatic changes were followed using activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen level, antithrombin III (ATIII) and protein C (PC) activities. Fibrinolytic activity was estimated by euglobulin lysis time and assays for plasminogen and fibrin/fibrinogen degradation products (FDP). These assays were performed before and after each autologous infusion and on days 2 and 3. Activated Mo and M psi expressed potent PCA (85.5 +/- 7.5 U/ml for MTP activated Mo and 50 +/- 5.3 U/ml for gamma IFN activated M psi suspensions). In both groups of patients, APTT, PT, and TT underwent no significant variations. There was no significant consumption of ATIII or PC, and fibrinolysis was not activated during the study period. In the group injected intraperitoneally with MTP-activated Mo, fibrinogen showed a significant and progressive increase in relation to the development of an inflammatory reaction, reaching a maximum average value of 6.1 g/l at the end of the therapy with a concomitant increase in FDP levels. This increase was not observed after intravenous therapy with gamma IFN-activated M psi. No patient suffered from hemorrhagic or thrombotic events. In our experience, repeated injections of activated Mo or M psi expressing potent tissue factor PCA did not induce significant in vivo activation of the coagulation system in cancer patients.
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PMID:Hemostatic changes in human adoptive immunotherapy with activated blood monocytes or derived macrophages. 132 42

Previous studies have demonstrated that platelets or aortic endothelial cells provide an appropriate surface that augments the proteolytic inactivation of factor Va by activated protein C (APC). We have examined the ability of three human tumor cell lines (HepG2, CAPAN-2 and J82) to support the inactivation of human factor Va by human APC in the presence and absence of human protein S. APC-mediated factor Va inactivation on these tumor cell lines was assessed by measuring the ability of residual cell-bound factor Va to augment the proteolytic activation of prothrombin by factor Xa. Each of the tumor cell lines studied supported factor Va inactivation by APC in the presence of calcium ions. HepG2 cell monolayers supported this reaction most effectively, with CAPAN-2 and J82 cell monolayers exhibiting moderate and weak effectiveness, respectively. Although not essential for this reaction, protein S moderately enhanced the rate of factor Va inactivation by APC on these tumor cell lines. In addition, pretreatment of each tumor cell line with rabbit antihuman protein S IgG had little, if any, effect on its ability to support factor Va inactivation by APC. Our data suggest that these, and perhaps other, tumor cells can provide an appropriate phospholipid surface for promoting factor Va binding and rapid inactivation by APC.
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PMID:Inactivation of factor Va by activated protein C on selected human tumor cell lines. 146 18

To determine the etiology of the increased incidence of postoperative deep venous thrombosis (DVT) in patients with carcinoma of the colon, serum levels of protein C were measured preoperatively in 65 patients with colorectal adenocarcinoma. Noninvasive lower-extremity Doppler studies were performed on all patients prior to discharge to assess patency of the deep veins. Six patients (9%) were found to have DVT. The protein C level was considered elevated if it was greater than 125% of control values and reduced if less than 75% of control values. The development of DVT was found to be independent of the serum carcinoembryonic antigen, albumin, total protein, hemoglobin, hematocrit, platelet count, prothrombin time, partial thromboplastin time, and the patient's age and percentage of ideal body weight. There was an inverse relationship between the protein C level (p less than 0.001), Dukes stage of the tumor (p less than 0.001), and the development of DVT. Linear regression analysis revealed that only the tumor stage and the protein C level could be used to predict the development of DVT. The data show that for these patients with colorectal malignancy, the development of DVT may be related to decreased levels of protein C.
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PMID:Protein C activity, stage of disease, and vascular thrombosis in colon carcinoma. 173 77

Infusion of tumor necrosis factor (TNF) into tumor-bearing mice led to intravascular clot formation with fibrin deposition in microvessels in the tumor bed in close association with the vessel wall, which could be prevented by active site-blocked factor IXa (IXai). This observation prompted us to examine the role of the intrinsic system in activation of the coagulation mechanism on TNF-stimulated human endothelial cell monolayers and endothelial-derived matrix during exposure to purified coagulation factors or flowing blood. Treatment of endothelial cells in intact monolayers with TNF induced expression of the procoagulant cofactor tissue factor (TF) in a dose-dependent manner, and after removal of the cells, TF was present in the matrix. TNF-treated endothelial cell monolayers exposed to blood anticoagulated with low molecular weight heparin induced activation of coagulation. Addition of IXai blocked the procoagulant response on TNF-treated endothelial cells, and consistent with this, the presence of factor IX/VIIIa enhanced endothelial TF/factor VII(a) factor X activation over a wide range of cytokine concentrations (0-600 pM). When TF-dependent factor X activation on endothelial cells was compared with preparations of subendothelium, the extracellular matrix was 10-20 times more effective. IXai blocked TF/factor VII(a) mediated activated coagulation on matrix, but only at lower concentration of TNF (less than 50 pM). Similarly, enhancement of factor Xa formation on matrix by factors IX/VIIIa was most evident at lower TNF concentrations. When anticoagulated whole blood flowing with a shear of 300 s-1 was exposed to matrices from TNF-treated endothelial cells, but not matrices from control cells, fibrinopeptide A (FPA) generation, fibrin deposition, and platelet aggregate formation were observed. FPA generation could be prevented by a blocking antibody to TF and by active site-blocked factor Xa (Xai) over a wide range of TNF concentrations (0-600 pM), whereas IXai only blocked FPA generation at lower TNF concentrations (less than 50 pM). Activation of coagulation on matrix from TNF-stimulated endothelial cells was dependent on the presence of platelets, indicating the important role of platelets in propagating the reactions leading to fibrin formation. These observations demonstrate the potential of cytokine-stimulated endothelium and their matrix to activate coagulation and suggest the importance of the intrinsic system in factor Xa formation on cellular surfaces.
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PMID:Activation of the coagulation mechanism on tumor necrosis factor-stimulated cultured endothelial cells and their extracellular matrix. The role of flow and factor IX/IXa. 205 Jul


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