Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrinogen and plasminogen were measured in plasma samples from prostatic cancer patients before and after 3 months of treatment with either Premarin, Provera, Provera and diethylstilbestrol, one of three doses of diethylstilbestrol, or placebo. Plasminogen levels generally were increased significantly with the estrogens but were unchanged following placebo or Provera treatment. Pretreatment plasminogen levels in Study 3 were significantly lower (p less than .001) than in Study 2. Plasminogen pretreatment levels were significantly correlated with age, hemoglobin, body weight, and blood pressure. Fibrinogen pretreatment levels were significantly elevated above normal. They were not significantly with age, hemoglobin, body weight, or blood pressure. Fibrinogen levels generally were significantly decreased by the estrogens. Comparisons of means of pretreatment fibrinogen and plasminogen levels from patients dying during the first year of the study with the mean pretreatment levels of the patient group alive after 1 year on study yielded no significant differences. Death rates were calculated by pretreatment plasminogen or fibrinogen for all treatments of all Stage III and Stage IV patients combined for Study 2 and Study 3 separately. Such rates were calculated for all causes combined and for deaths from prostatic cancer or cardiovascular disease separately. The levels of plasminogen were significnatly negatively correlated with death rate from all causes combined and with cardiovascular disease considered separately, but not with death from prostatic cancer. The levels of fibrinogen were signigicantly positively correlated with death rates from all cuses and nearly significantly with prostatic cancer, but not cardiovascular disease. Elvated pretreatment fibrinogen levels were associated with an increased proportion of deaths at 1 year from all causes and from cancer of the prostate.
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PMID:Response of plasma fibrinogen and plasminogen to hormone treatment and the relation of pretreatment values to mortality in patients with prostatic cancer. 18 48

Recent progress in elucidating the complex and heterogeneous interactions between malignancy and coagulation or fibrinolysis reactions in humans has clarified the pathogenesis of disseminated intravascular coagulation that occurs with malignancy and has revealed evidence for two distinct pathways of growth regulation based on production by tumor cells of initiators of thrombin formation versus plasminogen activators. We have proposed a preliminary classification of tumors (see Table 2) based on these interactions. Type I tumors are those in which the tumor cells are associated with an intact coagulation pathway that leads to thrombin formation at the tumor periphery but in which the tumor cells lack u-PA. Examples of tumors in this category include SCCL, malignant melanoma, and renal cell carcinoma. Type II tumors are those in which the tumor cells express u-PA but lack an associated coagulation pathway leading to thrombin formation. Examples of type II tumors include prostate cancer, colon cancer, breast cancer, and N-SCLC. Type III tumors are those that express neither of these pathways, or exhibit some other pattern of interaction. Obviously, this formulation must be regarded as hypothetical. However, this concept fits with the limited data available to date from clinical trials. More importantly, this hypothesis can be tested further by means of intervention aimed at interrupting pathways relevant to specific tumor types. Characterization of additional tumor types by the methods described should permit amplification of this classification of tumors and other patterns of interaction may be defined. Exploration of the coagulation-cancer interaction holds considerable promise for gaining new understanding of both the coagulation mechanism and tumor biology. Most intriguing is the prospect that imaginative approaches to cancer treatment may be devised that are not only relatively nontoxic and low cost, but also effective.
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PMID:Pathways of coagulation/fibrinolysis activation in malignancy. 157 11

To determine the relationship between cardiovascular complications of estrogen therapy and fibrinolysis, fibrinolysis parameters plasminogen, urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1), were assessed in 12 prostatic cancer patients before and 6 weeks after the onset of estrogen therapy. The levels of plasminogen, u-PA, and PAI-1 in the patients treated with the estrogen therapy were significantly higher than those in the patients before the therapy. The t-PA level in the patients during the therapy was significantly lower than that before the treatment. Cardiovascular complications were found in two patients (16.7%) during estrogen therapy. In the two patients, marked elevation of PAI-1 and decreased level of t-PA were observed during the therapy. These results indicate that cardiovascular complications of estrogen therapy in patients with prostatic cancer may be related to hypofibrinolysis resulting from changes of PAI-1 and t-PA.
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PMID:The relationship between cardiovascular complications of estrogen therapy and fibrinolysis in patients with prostatic cancer. 164 70

The levels of several tumor associated proteases, including plasminogen activators (PA), are elevated in many malignant tumors compared to their benign tumor counterparts. Extracellular matrix degradation mediated by PA may facilitate tumor cell invasion and metastasis. To assess whether PA content correlates with the aggressive phenotype in prostate cancer, we studied these activators in the PC-3 human prostate cell line and PC-3CALN, an aggressive in vivo derived variant cell line. Enzymatic assays using H-D-val-leu-lys-pNA (S-2251) as substrate and peroxidase-anti-peroxidase immunohistochemical techniques were used. In an in vitro chemoinvasion assay, the PC-3CALN variant cell line demonstrated significantly greater invasive behavior than the unselected, parental PC-3 line. The activity of PA secreted by PC-3CALN cells was 3.5 times greater than that of PC-3 cells (p less than 0.01). PC-3 metastases obtained following intrasplenic injection of PC-3 cells had greater PA activities than the corresponding primary tumors. Immunohistochemical studies of PC-3 tumors demonstrated preferential localization of urokinase-type PA to areas of apparent tumor cell invasion. These data suggest a correlation between PA and the aggressive phenotype in this model of human prostate cancer. PA, in particular u-PA, may play a role in the migration and invasion of prostate cancer cells and provide a marker of the aggressive phenotype.
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PMID:Plasminogen activators in human prostate cancer cell lines and tumors: correlation with the aggressive phenotype. 265 23

An analysis of haemostatic variables was done in 31 prostate cancer patients treated with oestrogens (13 pts), estramustine phosphate (7 pts) or orchidectomy (11 pts) before, at about 7 weeks and 6 months of treatment. Six patients treated with either of the drugs developed venous thromboembolism or ischemic vascular disease. Already before treatment there were changes indicating some activation of blood coagulation, fibrinolysis and kallikrein systems. The drug treated group showed significant changes in several variables: i.e. increase in factor VII, plasminogen and prekallikrein but also a decrease in antithrombin and in inhibitors to the fibrinolytic and kallikrein system. Significant difference between the drug treated groups was found in circulating platelet aggregates and in kallikrein inhibiting activity. Tissue plasminogen activator capacity was significantly lower in the drug treated patients with complications than in those without. The study also showed that in addition to the assay of the tissue plasminogen activator capacity during the first weeks of therapy it might be helpful in predicting cardiovascular complications to investigate platelet aggregates, prothrombin complex, factor X, von Willebrand factor antigen, fibrinogen, antithrombin, fibrino-peptide A, and the inhibitors of fibrinolysis as well as C1-esterase inhibitor.
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PMID:Changes in blood coagulation and fibrinolysis in patients on different treatment regimens for prostatic cancer. Predictors for cardiovascular complications? 312 58

Serum lipoprotein concentrations were related to hemostatic parameters in a group of 31 men before and during three different hormone treatment regimens for prostate cancer in an attempt to analyse to what extent the changes in these two systems correlate. In a correlation matrix the number of significant relationships at the 5% and 1% level corresponded to what could be expected by chance. The study thus failed to demonstrate any consistent relationship between any lipoprotein lipid concentration and the hemostatic parameters in men treated for prostate cancer. Most significant relationships were found for HDL-TG versus plasminogen, but the clinical significance of this observation is not clear.
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PMID:Relationship between serum lipoproteins and hemostatic parameters in men with prostatic cancer. 334 24

The treatment of prostatic cancer with oestrogen has been reported to be associated with cardiovascular side effects. Twenty patients with recently diagnosed prostatic cancer were randomly allocated to oestrogen therapy or orchidectomy. As compared to healthy age matched controls the patients with prostatic cancer had increased base-line levels of fibrinogen (5.2 +/- 1.9 g/l versus 3.7 +/- 1.0 g/l; p less than 0.002) and factor VIII:C (166 +/- 62% versus 110 +/- 29%; p less than 0.001). During oestrogen therapy factor VII increased from 99 +/- 22% to 150 +/- 47% (p less than 0.001), while the antithrombin III level fell from 93 +/- 10% to 81 +/- 13% (p less than 0.001). Both these changes are in the direction of a hypercoaguable state. Concomitantly plasminogen increased from 113 +/- 14% to 142 +/- 18% (p less than 0.001), urokinase inhibiting activity fell from 105 +/- 10% to 90 +/- 9% (p less than 0.001) and C1-esterase inhibitor fell from 110 +/- 17% to 86 +/- 22% (p less than 0.05) in the oestrogen therapy group. After orchidectomy there were no changes in the activators and inhibitors of coagulation and fibrinolysis studied as compared to base-line values. Furthermore the D dimer, a specific degradation product of crosslinked fibrin increased from a normal to a pathological value in 4 out of 8 tested patients after 6 weeks of oestrogen therapy, but in none out of 9 tested patients in the orchidectomy group. Briefly stated, patients with prostatic cancer treated with oestrogen have increased levels of factor VII, factor VIII:C and fibrinogen and a decreased level of antithrombin III.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activators and inhibitors of coagulation and fibrinolysis in patients with prostatic cancer treated with oestrogen or orchidectomy. 379 20

Hypofibrinogenemia and disseminated intravascular coagulation are common events in patients with metastatic prostate carcinoma. This study tests the hypothesis that prostate tumor growth and metastasis is associated with sustained activation of fibrinolysis secondary to increased release of plasminogen activator. We implanted an androgen-insensitive prostate tumor into an inbred strain of rats and serially measured plasminogen, plasminogen activator, plasmin and fibrinogen. Control groups included animals without tumor and a group implanted with transitional cell bladder carcinoma, a locally infiltrating tumor not usually associated with hemostatic complications. Our results showed a significant and steady rise in plasma plasminogen activator, plasmin and fibrinogen levels in animals implanted with prostate cancer. This, however, is not specific for prostate tumor. Similar, perhaps more profound changes were noted in animals implanted with the transitional cell carcinoma.
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PMID:The fibrinolytic system in experimental prostate tumor. 381 May 52

The presence of procoagulants and fibrin deposition have been demonstrated in malignant tumors. Although thrombin, a key enzyme in coagulation, has other various biological functions, the significance of its presence in tumors is not known. We studied the effects of thrombin on the expression of urokinase-type plasminogen activator (uPA) which is known to play a role in tumor invasion, using a human prostate cancer cell line PC-3. Human alpha-thrombin added to cultures of PC-3 produced a dose-dependent and time-dependent increased secretion of uPA that was greatest at 3-6 h after exposure to thrombin. Increase in uPA antigen paralleled the increase in mRNA level, which reached a maximum at 4 h. Thrombin showed the maximum effect on uPA expression at a concentration 1-2 units/ml. Zymography showed that transient exposure to thrombin induced an increase in fibrinolytic activity which could be quenched by anti-uPA antibody. The thrombin receptor-activating peptide also caused an increase in uPA protein and mRNA level, indicating the presence of the same thrombin specific receptor on PC-3 cells as on platelets and endothelial cells. Thrombin did not affect the expression of other components of the plasminogen activation system, tissue-type plasminogen activator and type-1 plasminogen activator inhibitor, and uPA receptor. These results indicate that thrombin increases uPA expression selectively by the stimulation of a functional thrombin receptor on PC-3 cells. Since uPA is known to play a role in pericellular proteolysis of extracellular matrix, thrombin may be involved in the regulation of tumor invasion and metastasis.
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PMID:Enhancement of the expression of urokinase-type plasminogen activator from PC-3 human prostate cancer cells by thrombin. 820 53

Angiostatin is an inhibitor of angiogenesis and metastatic growth that is found in tumor-bearing animals and can be generated in vitro by the proteolytic cleavage of plasminogen. The mechanism by which angiostatin is produced in vivo has not been defined. We now demonstrate that human prostate carcinoma cell lines (PC-3, DU-145, and LN-CaP) express enzymatic activity that can generate bioactive angiostatin from purified human plasminogen or plasmin. Affinity purified PC-3-derived angiostatin inhibited human endothelial cell proliferation, basic fibroblast growth factor-induced migration, endothelial cell tube formation, and basic fibroblast growth factor-induced corneal angiogenesis. Studies with proteinase inhibitors demonstrated that a serine proteinase is necessary for angiostatin generation. These data indicate that bioactive angiostatin can be generated directly by human prostate cancer cells and that serine proteinase activity is necessary for angiostatin generation.
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PMID:Human prostate carcinoma cells express enzymatic activity that converts human plasminogen to the angiogenesis inhibitor, angiostatin. 889 39


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