Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated protein C (APC) is inhibited by two major plasma inhibitors (PCIs). To find evidence for in vivo complexation of APC, immunoblotting studies were performed on plasmas of 85 patients with suspected disseminated intravascular coagulation (DIC). Samples from 62 of these patients contained 5% to 35% of protein C antigen in APC:inhibitor complexes, indicating that protein C activation and inhibition had occurred. In 24 normal plasmas, no detectable APC:PCI complexes were observed (less than 5%). Patients with higher levels of complexes had more abnormal coagulation test data for DIC. The major band of APC complexes detected by anti-protein C antibodies did not react with antibodies to the heparin-dependent protein C inhibitor (PCI-1) previously described. Rather, APC was complexed with another recently described plasma protein C inhibitor, PCI-2. Immunoblotting studies for protein S, the cofactor for APC, revealed that the majority of the DIC patient plasmas contained a higher than normal proportion of protein S in cleaved form, suggesting that protein S may have been proteolytically inactivated. Protein S total antigen levels were also found to be low in DIC patients, excluding those with malignancy. These studies support the hypothesis that the protein C pathway is activated during DIC.
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PMID:Activation and complexation of protein C and cleavage and decrease of protein S in plasma of patients with intravascular coagulation. 252

Mean plasma concentrations of the main inhibitors of blood coagulation antithrombin III (AT III), protein C and protein S were determined in 149 patients with different local and disseminated malignancies. Results were compared with findings in 44 healthy subjects. No statistical significant differences for AT III, protein C and free protein S were found between patients and controls. However, total protein S showed a significant increase in the patient group (p less than 0.0003). None of the parameters analyzed showed differences according to the degree of tumoral activity nor to the tumour localization. We conclude that the main inhibitors of the blood coagulation seem not to play an important role in the pathogenesis of the hypercoagulable state in malignancy. The increased levels in total protein S would indicate endothelial synthesis in response to thrombogenic stimuli.
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PMID:[Coagulation inhibitors in patients with neoplasms]. 252 31

A research project initiated in 1978 comprised establishment of a national polyposis registry, a genetic linkage study using classical and DNA markers, an in vitro study of fibroblasts for transformation parameters and chromosome instability, and a comparative study of DNA-RFLPs in cancer and constitutional tissue. The linkage study (to be reported elsewhere) confirmed the recently reported close linkage between the polyposis gene locus APC and D5S71. No in vitro test for the presence of the APC gene has been confirmed or revealed, but we detected increased chromosomal instability on a statistical basis and also recorded abnormal DNA-repair. As per 1. January 1988 the prevalence of adenomatosis of colon and rectum in Norway was 1/43,500. Among patients born in the period 1931-1950 the incidence at birth of developing the disease is 1/20,000 and the mutation rate is 1/72,000 per gamete per generation. In Norway new mutants in healthy families will comprise 1/3-1/2 of all new cases in the coming two decades, or one of 36,000 births.
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PMID:[The polyposis project]. 253 47

We performed a blood coagulation study during the course of disseminated intravascular coagulation (DIC) in 34 patients with hematological malignancies. Risk factors of DIC such as increasing tumor mass, anti-tumor therapy and severe infections were frequently observed at onset of DIC, and influenced the prognosis of DIC. Before the onset of DIC, the DIC score and FDP value were slightly elevated, and they were significantly increased after the onset of DIC. Before the onset of DIC, the level of fibrinogen was significantly increased but it was decreased after the onset of DIC. These hemostatic abnormalities continued for about 2 weeks. Patients with DIC showing prolonged APTT and PT had a poor prognosis. The abnormalities of PT, FDP, fibrinogen, DIC score, FDP-D-dimer and fibrinopeptide A were significantly greater in DIC than in Pre-DIC defined as the period one week before the onset of DIC. FDP-D-dimer was also higher in Pre-DIC patients than in those without DIC. Although protein S and C 4 b binding protein were not decreased in DIC or Pre-DIC, Protein C activity decreased during the course of DIC, suggesting that FDP-D-dimer and Protein C activity were useful for diagnosis of Pre-DIC and DIC.
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PMID:[Hemostatic changes before and after the onset of disseminated intravascular coagulation]. 259 41

Serial determinations of plasma coagulation inhibitor levels were performed with chromogenic substrate activity assays in 7 patients with cancer. At time of diagnosis normal median activities of Antithrombin, Protein C, Heparin Cofactor II and Extrinsic Pathway Inhibitor were found. The inhibitor activities changed significantly with the progress of malignant disease; Antithrombin, Protein C and Heparin Cofactor II decreased whereas Extrinsic Pathway Inhibitor increased. Determinations in 13 additional patients in the terminal phase of cancer confirmed this finding. The inhibitor activities were expressed in per cent of a pooled reference plasma. In the total series of 20 patients studied, median activity of Extrinsic Pathway Inhibitor was 183% (range 61-378%) and significantly (p less than 0.005) above age-adjusted normal reference 10 days (range 1-20 days) prior to death. Median activities of Antithrombin was 59% (range 20-109%), of Protein C 54% (range 24-130%) and Heparin Cofactor II 59% (range 33-110%), all significantly below age adjusted normal reference (p less than 0.001). The coagulation inhibitor levels seem related to the stage of disease in patients with cancer.
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PMID:High plasma levels of extrinsic pathway inhibitor and low levels of other coagulation inhibitors in advanced cancer. 259 46

Several investigators have reported that tumor necrosis factor (TNF) can alter the hemostatic properties of vascular endothelial cells in vitro. We have examined the in vivo effects on the hemostatic mechanism of recombinant human TNF administered as a continuous intravenous infusion to 23 cancer patients with active disease. A battery of sensitive and specific immunochemical techniques were used to monitor changes in blood coagulability. Serial determinations of F1 + 2, the protein C activation peptide (PCP), and fibrinopeptide A (FPA) were obtained prior to the initiation of the TNF infusions and at three and 24 hours after the start of therapy in 12 individuals who received greater than 3 x 10(5) U/m2/24h. The mean levels of F1 + 2, PCP, and FPA were significantly elevated at both time points as compared to the baseline values. The metabolic behavior of 125I-F1 + 2 in an animal model was not affected by infusions of the cytokine. We therefore conclude that the observed elevations in the concentration of this marker in humans receiving TNF result from hemostatic system hyperactivity. In 11 subjects infused with 1 x 10(5) to 2.4 x 10(5) U/m2/24 h of the cytokine, the mean levels of F1 + 2, PCP, and FPA were not significantly greater at 24 hours as compared with the baseline values, indicating that there is a threshold dose at which the cytokine can exert a biochemical effect on the coagulation system. Our studies demonstrate that TNF is able to provide a substantial net procoagulant stimulus to the hemostatic mechanism, and suggest that this cytokine may be a mediator of certain hypercoagulable states in humans.
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PMID:Tumor necrosis factor infusions have a procoagulant effect on the hemostatic mechanism of humans. 275 8

18 elderly patients submitted to major surgery for malignancies or other disease were studied to assess the relationship between changes of blood coagulation factors and inhibitors in the early post-operative period and the appearance of lower limb deep vein thrombosis. A decrease in serum antithrombin III (AT III) Protein C antigen (PC: Ag) and Plasminogen activity (PLG) levels from the second to the fourth postoperative day, together with a simultaneous increase in serum fibrinogen (FG) and von Willebrand Factor (vWF:Ag) antigen levels was observed. In 8 patients, PC:Ag levels dropped below the limit considered at risk to develop DVT (less than 60 U/dl). A patient with the lowest PC:Ag levels had deep vein thrombosis From the analysis of data it was concluded that in the postoperative period, blood coagulation changes occur in elderly patients, predisposing to the risk of deep vein thrombosis.
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PMID:Evaluation of postoperative blood coagulation changes in elderly patients undergoing major surgery. 278 5

Recent reports have documented an increase of thrombotic complications in patients with carcinoma of the breast receiving chemotherapy regimens containing cyclophosphamide, methotrexate, and 5-fluorouracil. The authors studied blood from nine such patients screening for abnormalities that might predispose to thrombosis or indicate that the coagulation cascade had been activated. Six of the patients were in the adjuvant setting, and three had metastatic disease. Samples were collected from each patient before, during, and after completion of the chemotherapy in question. In each patient a statistically significant decline in functional protein C activity (P = 0.001) was demonstrated at midtherapy. In seven of nine patients functional protein C level normalized after the cessation of therapy. No other positive results were found. The authors conclude that the combination of cyclophosphamide, methotrexate, and 5-fluorouracil, when administered to patients with a diagnosis of carcinoma of the breast, causes a reversible decline in the activity of protein C.
Cancer 1989 Apr 01
PMID:Acquired protein C deficiency in patients with breast cancer receiving cyclophosphamide, methotrexate, and 5-fluorouracil. 292 Mar 59

Patchy necrosis of the skin is a rare and unpredictable complication of oral anticoagulant therapy. Of the four patients that we have seen with this disorder, three had metastatic adenocarcinoma; in two, this was an unexpected finding. The association of a malignant neoplasm with warfarin-induced skin necrosis has not been emphasized previously. Whether such necrosis represents a clue to the presence of cancer or occurs only coincidentally in patients requiring anticoagulant therapy because of adenocarcinoma-associated thrombophlebitis must await further experience. A congenital or acquired deficiency of protein C may be the primary initiating factor.
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PMID:Warfarin-induced skin necrosis. A cutaneous sign of malignancy? 293 93

Using a new rapid coagulant method, protein C activity (PC act) was determined in liver cirrhosis and malignancies and compared with PC antigen and AT III values. PC was decreased in a more pronounced manner than AT III in liver cirrhosis, mainly due to impaired synthesis. This is of special clinical interest because PC proved to be a high sensible indicator of liver cell dysfunction. Decreased levels of PC act (PC ratio act/ag less than 1) in decompensated liver cirrhosis may be caused by the synthesis of dysfunctional PC and/or vitamin K deficiency with production of undercarboxylated PC most sensitively registered by this coagulant assay. An increased clearance of in vivo activated PC induced by DIC may play an insignificant role. In patients with liver metastases, PC act (but not AT III and immunological parameters) was significantly reduced, supporting the conclusion that in these patients liver dysfunction concomitant with synthesis of dysfunctional PC must be discussed as the main cause of this alteration.
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PMID:Immunological and functional determination of the protease inhibitors, protein C and antithrombin III, in liver cirrhosis and in neoplasia. 320 4


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