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)

Sixteen patients with clinically localized breast carcinoma who had been receiving tamoxifen 20 mg twice daily for between 3 and 38 months (median, 14 months) were studied. Several parameters of coagulation (antithrombin III, protein C, fibrinopeptide A and in vitro monocyte procoagulant activity) were investigated in this group and compared to a group of 15 patients with clinically localised breast carcinoma not given tamoxifen. Tamoxifen did not induce significant changes in these parameters to account for the reported thromboembolic events associated with this therapy. The reduced antithrombin III activity previously described in patients receiving tamoxifen for metastatic breast cancer may reflect disease activity rather than a direct effect of tamoxifen on blood coagulation.
Cancer 1988 Apr 01
PMID:Effects of tamoxifen on blood coagulation. 334 87

Hemostatic abnormalities are common in patients with metastatic malignancy and are attributed, in part, to materials secreted by tumor cells. Tumor stimulation might therefore cause further perturbation of hemostasis. This article reports observations on the effects of androgen stimulation on multiple hemostatic parameters in patients with metastatic prostate cancer. Testosterone was given before chemotherapy in an experimental protocol designed to increase tumor sensitivity to cytotoxic agents. The following parameters were measured on day 0 (before) and days 2 and 4 of fluoxymesterone administration: PT, APTT, platelet count, plasma betathromboglobulin (BTG), platelet factor 4 (PF4), fibrinogen, fibrin(ogen) split products (FSP), factor VIII coagulant activity (VIII C), von Willebrand factor antigen (vWF Ag), fibrinopeptide A (FPA), antithrombin III (AT III), and protein C antigen (PC). Ten patients were studied during 17 cycles of hormonal stimulation. Baseline levels of BTG, PF4, fibrinogen, FSP, factor VIII C, vWF Ag, and FPA were significantly elevated compared with normal control. Although androgen stimulation resulted in elevation of BTG, FPA, and FSP levels by day 4 in many patients, the changes for the entire group were not statistically significant. Other parameters remained unchanged or were only slightly elevated. Two patients developed laboratory evidence of disseminated intravascular coagulation (DIC) but were clinically unaffected. Our data suggest that most patients with metastatic prostate cancer show evidence of ongoing activation of platelets, coagulation, and fibrinolysis. In a few individual patients, androgen stimulation of this hormonally dependent tumor may cause further activation of platelets, coagulation, and fibrinolysis.
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PMID:Hemostatic effects of hormonal stimulation in patients with metastatic prostate cancer. 340 35

The subcellular localization of protein kinase C and the ability of phorbol esters to alter cell phenotype were examined in the U937 monoblastic cell line. Protein kinase C activity was evaluated using an in vitro assay measuring histone phosphorylation in the cytosolic and detergent extracted particulate fractions obtained after disrupting cells that had been cultured previously under varying conditions. Depriving cells of serum for 2-3 days resulted in a time-dependent decrease in protein kinase C activity of the particulate fraction. The addition of as little as 0.5-1% fetal bovine serum to serum-deprived cells increased protein kinase C in the particulate fraction by up to 2- to 3-fold. In contrast lipoprotein-deficient serum did not mimic the effect of whole serum. However addition of high or low density lipoproteins to cells grown in lipoprotein-deficient serum or serum-free medium produced a concentration-dependent 2- to 3-fold increase in particulate protein C kinase activity. The maximal lipoprotein effect was similar to that observed with 5% fetal bovine serum and the concentrations of lipoproteins needed to increase protein kinase C activity were in the physiological range. Adherence to plastic was used as a marker of the differentiated phenotype. Cells cultured in lipoprotein-deficient serum did not differentiate in response to phorbol ester stimulation as well as cells cultured in 5% fetal bovine serum. These results suggest that serum lipoproteins modulate protein kinase C localization and the response to phorbol ester stimulation in the U937 cell.
Cancer Res 1986 Dec
PMID:Lipoprotein modulation of the intracellular localization of protein kinase C and alteration of phorbol ester-stimulated differentiation in the human monoblastic U937 cell line. 346 31

Protein C is, after activation by thrombin, a potent inhibitor of blood coagulation. An isolated deficiency of protein C increases the risk of thrombosis. The two forms of protein C deficiency, the heterozygous and the homozygous deficiency state, have different clinical features. Patients with heterozygous protein C deficiency are at a high risk to develop venous thrombosis and pulmonary embolism. In newborns with homozygous protein C deficiency with very low protein C levels (1%) a purpura fulminans like syndrome was observed. Heparin and coumarin derivatives are effective drugs in heterozygous protein C deficiency, homozygous patients may be treated either by replacement of protein C or coumarin derivatives. Decreased protein C levels were observed in various other diseases: Chronic and acute liver disease, disseminated intravascular coagulation, malignancy, postoperatively and during treatment with asparaginase. The role of protein C in these diseases to trigger thrombosis is not yet established.
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PMID:Clinical relevance of protein C. 352 11

In Japan, the various hemostatic medicines have been used after operation. On the contrary, in Europe and U.S.A., the anticoagulants are used both before and after operation because of the high incidence of postoperative deep vein thrombosis. We made inquiries about how they have been used to 566 main surgical clinics in Japan. In the half of these surgical facilities, these medicines still have been used routinely. But in 16.9% of surgery, 9.5% of obstetric & gynecological operation and 29.4% of orthopedic surgery, they have never been used at all. In the field of surgery, in 42% of cardiovascular, 32.1% of respiratory and 10.8% of general surgery, they have not been used absolutely. For the patients with liver cirrhosis, obstructive jaundice and the patients who received the massive blood transfusion during operation, more than 80% of facilities have used the hemostatic medicines. After operation, the blood becomes hypercoagulable and tends to form thrombosis, because of increasing coagulability, decreasing AT-III and protein C, hyper-function of platelet, hypofibrinolytic state and high viscosity. Especially cancer patients have the high risk of deep vein thrombosis. Also we investigated the difference of the incidence of the hemorrhagic complications after operation between in the hemostatic drug group and no drug one. No significant difference was observed. It is concluded that the use of hemostatic medicines after operation is not recommended.
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PMID:[Is it necessary to administer hemostatic medicines after surgical operation? The results of questionnaires about the use of hemostatic medicines in Japan]. 380 75

Out of necessity and convenience many reports on population-based rates for cancer are limited to analyses by time period of diagnosis, and just how often cohort effects are important in cancer data has not been fully explored. To address this question, Connecticut cancer incidence rates for the years 1940-79 were fitted to the model: Log (incidence rate) = constant + age effect + period effect + birth cohort effect + error term. Data for each cancer site and sex were categorized into 10-year intervals by time period and age group. Significance testing for the curvilinear effects (which are estimable functions) of age (A), period (P), and cohort (C) in the 44 data sets led to no clear choice of model for three data sets; an APC model for 20, an AP model for 7, and an AC model for 14. These choices were corroborated by the RA2 index. Limitations in the interpretation of the results were enumerated. Presentation of population-based cancer rates by implicitly assuming an AP model is valuable (e.g., for studying age distribution in different regions or for age-adjustment in examining international variation or time trends). However, the assumption of an AP model may often be incorrect, as was shown to be the case for most of these 44 data sets. The implications for monitoring trends and generating etiologic hypotheses were discussed in light of the results for cutaneous malignant melanoma and cancers of the cervix, breast, ovary, lung, and bladder.
J Natl Cancer Inst 1985 Apr
PMID:Time period compared to birth cohort in Connecticut incidence rates for twenty-five malignant neoplasms. 385 75

Activated protein C is a potent inhibitor of coagulation, and familial protein C deficiency has been associated with recurrent venous thrombosis. We have investigated protein C antigen levels in patients undergoing major elective abdominal surgery, to determine their relationships to postoperative deep vein thrombosis (DVT), malignancy, and preoperative treatment with intramuscular or oral stanozolol. Preoperative and postoperative protein C levels were not significantly different in patients with and without DVT (detected by 125I-fibrinogen leg scans), nor in patients with and without malignancy. In a placebo group (n = 26), a significant fall in protein C was maximal on the first postoperative day and persisted for 7 days. In a group given intramuscular stanozolol, 50 mg on the preoperative day (n = 23) stanozolol shortened the duration of the postoperative fall in protein C, but did not prevent DVT. In a group given oral stanozolol, 10 mg/day for 2 weeks before and 1 week after operation (n = 11), stanozolol significantly increased protein C levels prior to surgery, hence maintaining protein C at pretreatment levels after surgery. The effect of this regimen on the incidence of DVT is under study.
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PMID:Protein C antigen levels in major abdominal surgery: relationships to deep vein thrombosis, malignancy and treatment with stanozolol. 391 79

Activation of the APC is pointed out as the common factor in all sufficiently studied cancer treatments employing nonspecific, active immunotherapy. This chapter outlines the molecular biology of both APC and classical pathway of complement, summarizes the alternative pathway's biologic activities especially in relation to the C3/C5 convertase C3b,Bb, and its implications in the mechanism of host defense against malignancies, particularly relating to the activated macrophage. The many involvements of the APC in the various agents used for nonspecific active immunotherapy are reviewed, and possible clinical implications outlined. It is concluded that activation of the APC can be proposed as the specific theoretical basis so far lacking for this treatment modality and that it is accordingly feasible to attempt to monitor clinical application of this principle by fine-tuning of APC activation in cases of human cancer.
Adv Immun Cancer Ther 1985
PMID:Complement and cancer: activation of the alternative pathway as a theoretical base for immunotherapy. 391 62

Protein C is a vitamin-K-dependent plasma glycoprotein that when activated inhibits coagulation by selectively inactivating the active forms of factor V and factor VIII. A specific antiserum to protein C has been raised, and plasma protein C levels have been measured by means of an electroimmunoassay in several physiological and pathological conditions. In 60 healthy adults there were no differences in protein C related to age or sex; protein C levels ranged from 72 to 139% of values in a normal plasma pool. Low levels were found in 12 healthy full-term newborn infants; the levels in 20 women in the last trimester of normal pregnancy were no different from those in healthy non-pregnant women. In 58 patients with chronic liver diseases protein C levels were lower than those in healthy subjects, in degrees roughly proportional to the severity of the disease. Protein C levels were very low in 21 patients with the disseminated intravascular coagulation syndrome, particularly in those who had evidence of consumption coagulopathy. Very low levels were also found, however, in 20 patients with adult respiratory distress syndrome without consumption coagulopathy. Acquired defects of protein C developed after surgery in the patients operated on for malignancies, after major abdominal operations for benign conditions, and also after relatively minor procedures such as appendicectomy and hernia repair. These findings indicate that protein C deficiencies occur in several conditions associated with increased tendency to thrombosis.
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PMID:Deficiencies of protein C, an inhibitor of blood coagulation. 612 39

The authors report their experience with 45 cases of inferior vena cava thrombosis. Diagnosis was delayed for an average of 55 days. One-third of cases were revealed by an embolic complication. Inflammatory diseases were the most common causes (Behcet disease: seven cases, systemic lupus erythematosus: 5 cases). Malignancies accounted for 20% of cases. Abnormalities of coagulation were uncommon: antithrombin III deficiency in one patient and protein C deficiency in another. Estrogen-progestogen combinations could be incriminated in 4 cases. Outcome was fatal in 20% of cases, usually as a result of the underlying disease. Functional status was good in two-thirds of patients without malignancy followed up for an average of 27 months. In 14 patients a clip was inserted to ensure total (3 cases) or partial (11 cases) interruption of vena cava blood flow because of a free thrombus and/or recurrent pulmonary embolism. Three patients had thrombectomy. After clip insertion two embolisms were recorded, one of which occurred in the immediate post-operative period.
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PMID:[Inferior caval syndromes. Apropos of 45 cases]. 632 Apr 31


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