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)

Cholesterol and triglycerides were measured in plasma samples from patient with cancer of the prostate before and after 3 months treatment with either Premarin, Provera, Provera and diethylstilbestrol, or diethylstilbestrol alone. Cholesterol was also measured before and after one of three doses of diethylstilbestrol or placebo. Pretreatment cholesterol levels at 196 +/- 1.3 mg per 100 ml (X +/- SE, N = 1093) were significantly lower than these reported for similar age group noncancer controls. Significant increases occurred with some of the estrogen treatments. Pretreatment cholesterol levels showed a significant negative correlation with age in Stage III and IV patients of both studies and a positive correlation with hemoglobin in Stage III patients of both studies. Pretreatment triglyceride levels at 120 +/- 1.9 mg per 100 ml (X +/- SE, N = 1089) were similar to levels reported for noncancer controls of similar age. Estrogen treatment produced a significant increase in triglyceride levels. Serum triglycerides were significantly correlated with hemoglobin, weight, and cholesterol and negatively correlated with age, Analysis of covariance for both cholesterol and triglycerides showed highly significant treatment effects, but no stage effects and no stage-treatment interactions. It showed that the pretreatment value is of extreme importance for predicting or explaining the 3-month value. Death rates were calculated by level of pretreatment cholesterol or pretreatment triglycerides for all Stage II and IV patients, all treatments combined, and for Study 2 and Study 3 separately. No consistent trends were evident for cholesterol. Spearman correlation coefficients between category of initial triglyceride value and rank of death rate were computed to test for a quadratic effect. When the absolute values of the initial triglyceride values minus the overall mean were correlated with the death rate, a significant negative correlation was found for all causes of death and for deaths due to cardiovascular disease and prostatic cancer. These results indicate that the death rate is highest near the overal mean for initial triglyceride values and decreases as the initial values deviate above or below the mean. Initial triglyceride levels appear to have potential as indicators of risk of death in patients with prostatic cancer. The percentage of patients dead at 1 year by initial triglyceride levels, measured only in Study 3, revealed a pattern similar to that observed for the death rate, that is, the highest percentages were associated with values near the overall mean.
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PMID:Response of serum cholesterol and triglycerides to hormone treatment and the relation of pretreatment values to mortality in patients with prostatic cancer. 18 47

Ketoconazole, an antifungal antibiotic, inhibits cholesterol synthesis by blocking demethylation of lanosterol. Effects of this inhibition were studied on serum cholesterol, lipoproteins and cholesterol precursors, biliary lipid composition, and fecal steroid elimination in five patients with prostate cancer treated with large doses of ketoconazole. The serum level of total cholesterol fell by 27%, that of LDL cholesterol by 41% and that of LDL apoB by 32% with ketoconazole alone; the fall in the total cholesterol level of a patient treated with ketoconazole-cholestyramine was 65%. Serum contents of free lanosterol and dihydrolanosterol increased up to 250 times, yet the total concentrations remained less than 2 mg/dl. Of the other cholesterol precursor sterols only those with delta 8-double bond increased several times, indicating that in addition to 14 alpha-demethylation, ketoconazole also interfered with metabolism of later intermediary sterols to some extent. Compared with serum sterols, lanosterols were enriched in biliary and fecal sterols up to 10-20 times. Fecal lanosterol output increased from 12 to 247 mg/day, and comprised over 20% fecal steroids of endogenous origin. Bile acid synthesis was significantly decreased, the proportion of chenodeoxycholic acid being markedly reduced in both biliary and fecal bile acids. Cholesterol absorption appeared to decrease yet fecal neutral sterol output and cholesterol synthesis were unchanged and the overall sterol synthesis was increased. It thus appears that ketoconazole inhibits cholesterol elimination as bile acids. However, by blocking 14 alpha-demethylation, it results in effective drainage of sterol nucleus as lanosterols into bile and feces, which, in turn, is associated with a marked reduction in low density lipoprotein (LDL) cholesterol level probably through activation of hepatic LDL apoB receptors.
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PMID:Cholesterol metabolism during ketoconazole treatment in man. 335 51

Incidence rates for many sites of cancer show wide variations among the main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos, and Hawaiians). Major shifts in cancer rates among migrants to the islands suggest that environmental factors are at least in part responsible for these variations. One prominent area of difference among these ethnic populations is their diets, which can vary substantially, not only in the consumption of particular food items but also in mean nutrient intakes. In aggregate correlational analyses based on data from representative samples of these ethnic groups and corresponding population-based cancer incidence rates, we found significant associations between ethnic-sex-specific intakes of dietary fat (including total fat, as well as animal, saturated, and unsaturated fats) and breast, endometrial, and prostate cancers. Animal protein intake showed associations similar to those for dietary fat, but these two nutrients were highly correlated in the data. Cholesterol intake showed significant correlations with lung and laryngeal cancers. Analyses of both nutrient and food item data suggested an association of stomach cancer incidence with the consumption of fish products, particularly dried/salted fish, and with a lower intake of vitamin C. Preliminary findings from ongoing case-control studies showed the following relationships: an inverse association between lung cancer risk and the intake of food sources of vitamin A, especially foods containing carotenes; an inverse association between cancers of the lower urinary tract and vitamin A consumption, especially from supplements; a positive association between prostate cancer risk and dietary fat intake in men above age 69, but not in younger men; and a positive association between breast cancer risk and the intake of dietary fat (particularly saturated fat) and animal protein in postmenopausal women, especially the Japanese. Two large cohorts (50,000 and 5,000 subjects) on whom dietary information was collected between 1975 and 1980 are being followed prospectively for their occurrence of cancer.
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PMID:Role of diet in cancer incidence in Hawaii. 683 63

Average daily intakes of several components of fat in the diets of the five main ethnic groups in Hawaii were determined from personal interviews of 4137 subjects regarding their food consumption in a usual week. In general, fat intake was highest among Caucasians and lowest among Filipinos. Cholesterol intake did not follow the same pattern as that of the other fat components. The intake of total fat showed good correlation with the ethnic-specific incidence rates of breast cancer in Hawaii but not with colon or prostate cancer rates. There was no correlation of cholesterol intake with colon cancer incidence.
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PMID:Dietary fat intake and cancer incidence among five ethnic groups in Hawaii. 726 Sep 32

The incidence of cardiovascular disease is lower in women than in men, but is raised in men with prostatic cancer treated with estrogens. Changes of the plasma lipoproteins are related to the development of ischaemic cardiovascular disease and can be brought about by hormonal treatment. We have therefore studied plasma lipoproteins during estrogen treatment and after orchidectomy. 16 patients with prostatic carcinoma were treated with ethinyl estradiol daily by mouth and polyestradiol phosphate intramuscularly once a month. 15 other patients were treated by bilateral orchidectomy. Cholesterol (C), triglyceride (TG), and phospholipid (PL) concentrations in plasma and in the very low density (VLDL), low density (LDL) and high density lipoprotein (HDL) fractions were determined before starting treatment and 2 weeks and 8 weeks later. In the estrogen treated group the mean plasma C concentration decreased by 14 and 10%, while the mean HLD-C increased by 23 and 53%, and the mean LDL-C decreased by 24 and 25% at 2 and 8 weeks respectively. The mean PL concentration in HDL increased by 36 and 79% while that in LDL decreased by 12 and 18%. The mean plasma TG concentration was increased by 36 and 46%, mainly reflecting a rise of TG in the HDL-LDL fraction. Orchidectomy created only slight changes of plasma lipids. After 8 weeks the mean C concentration in plasma was raised by 10% and the mean PL concentration by 11%, owing to a 13% rise in the mean HDL-PL level. The changes in plasma lipoprotein pattern created by high doses of estrogens are mainly thought to protect against the development of atherosclerosis. The slight changes that take place after orchidectomy can hardly affect the incidence of cardiovascular disease.
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PMID:Plasma lipoproteins during anti-androgen treatment by estrogens or orchidectomy in men with prostatic carcinoma. 726 28

The incidence of cardiovascular disease is lower in women than in men, but is raised in men with prostatic cancer treated by estrogens. The antiandrogenic gestagenic drug, cyproterone acetate, is sometimes used instead of estrogens in the treatment of prostatic cancer. The cardiovascular risk associated with such hormonal treatment has been debated. Changes in plasma lipoproteins are related to the risk of cardiovascular disease and can be brought about by hormonal treatment. Plasma lipoproteins were therefore investigated during cyproterone acetate therapy in 15 men with prostatic cancer. Cholesterol (C), triglyceride, and phospolipid (PL) concentrations were determined in the very low density, low density (LDL), and high density lipoprotein (HDL) fractions. During treatment, mean body weight decreased by 1.2 and 1.9 kg after 2 and 8 weeks, respectively. The mean C concentration was lowered by 16%. The HDL C was reduced by a mean of 25%, and the LDL C decreased by means of 15% and 10%. The part of plasma C carried in the HDL fraction decreased slightly from 19 to 17% (mean) and the mean HDL C/LDL c quotient was lowered from 0.27 to 0.22. The mean PL concentration in plasma was decreased due to a mean reduction of HDL-PL by 17% and LDL Pl by 10%. A reduction of the HDL/LDL quotient implicates an increased risk for development of atherosclerotic diseases. However, it seems unlikely that a modest reduction in the HDL/LDL quotient, as obtained by cyproterone acetate, should have any great influence on the incidence of cardiovascular disease in elderly men with prostatic carcinoma.
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PMID:Plasma lipoproteins during treatment with cyproterone acetate in men with prostatic carcinoma. 741 87

Diazepam-binding inhibitor/acyl-CoA-binding protein (DBI/ACBP), a highly conserved 10-kDa polypeptide, has been implicated in various physiological processes including gamma-aminobutyric acid type A receptor binding, acyl-CoA binding and transport, steroidogenesis, and peptide hormone release. Both in LNCaP prostate cancer cells and 3T3-L1 preadipocytes, the expression of DBI/ACBP is stimulated under conditions that promote lipogenesis (treatment with androgens and insulin, respectively) and that involve the activation of sterol regulatory element-binding proteins (SREBPs). Accordingly, we investigated whether DBI/ACBP expression is under the direct control of SREBPs. Analysis of the human and rat DBI/ACBP promoter revealed the presence of a conserved sterol regulatory element (SRE)-like sequence. Gel shift analysis confirmed that this sequence is able to bind SREBPs. In support of the functionality of SREBP binding, coexpression of SREBP-1a with a DBI/ACBP promoter-reporter gene resulted in a 50-fold increase in transcriptional activity in LNCaP cells. Disruption of the SRE decreased basal expression and abolished SREBP-1a-induced transcriptional activation. In agreement with the requirement of a co-regulator for SREBP function, transcriptional activation by SREBP-1a overexpression was severely diminished when a neighboring NF-Y site was mutated. Cholesterol depletion or androgen treatment, conditions that activate SREBP function in LNCaP cells, led to an increase in DBI/ACBP mRNA expression and SRE-dependent transcriptional activation. These findings indicate that the promoter for DBI/ACBP contains a functional SRE that allows DBI/ACBP to be coregulated with other genes involved in lipid metabolism.
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PMID:Identification of diazepam-binding Inhibitor/Acyl-CoA-binding protein as a sterol regulatory element-binding protein-responsive gene. 968 28

Laboratory tests are key indicators for certain practice guidelines, and analytic bias can significantly alter the performance of these guidelines. Three clinical paradigms are described: serum cholesterol testing for risk assessment of cardiac disease, serum thyroid-stimulating hormone (TSH) measurement for the detection of hypothyroidism, and serum prostate-specific antigen (PSA) testing for prostate cancer risk assessment. Maximum tolerance limits for analytic bias are calculated by assessing the subgroup population fluctuations in the number of patients exceeding the guideline threshold values and limiting the analytic bias to one-half of these fluctuations. Our calculated maximum bias limits are +/-1% for cholesterol and +/-6% for TSH and PSA. Our recommended +/-1% bias limit for cholesterol allows for a -6.5% to + 5.8% change in the number of patients designated as at risk for cardiac disease, whereas the +/-3% National Cholesterol Education Program limits permit a -18.4% to +16.7% variation. Similarly, our +/-6% bias limits for TSH allow a -17.7% to +26.6% change in patients flagged for hypothyroidism, whereas the +/-10% bias values found with many commercial reagents permit a -28.2% to +49.2% variation in patient classification. Our +/-6% PSA bias limits correspond to changes from -14.2% to +11.4% in the number of men classified as at risk for prostate cancer. The +/-10% bias ranges for PSA correspond to -19.9% to +20.4% variation in patient classification. The larger tolerance limits of the CLIA-88 standards for proficiency testing would cause even wider variations in patient classifications.
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PMID:Analytic bias specifications based on the analysis of effects on performance of medical guidelines. 1066 88

Androgens, diet, race and obesity are thought to play some roles in the pathogenesis of prostate cancer. We wanted to evaluate if there were any inter-relationships between prostate specific antigen (PSA), serum testosterone, serum cholesterol, HDL, triglycerides, body mass index (BMI) and race, in older patients with and without prostate cancer (CaP). We evaluated 308 patients referred to urologists in private practice offices and clinics with and without prostate cancer with regard to race, serum PSA, age, serum testosterone, full lipid profile, height and weight, and stage of cancer. We used multivariate analysis, Fisher's exact test and t-tests as well as logistic regression analysis. Data was analyzed using SPSS computer software, and P-values<0.05 were considered statistically significant. Significantly higher levels of serum testosterone were found in black men with CaP than black men without CaP (526+/-28 vs 404+/-19, respectively.) We also found significantly higher levels of serum testosterone in white men with CaP than white men without CaP (409+/-20 vs 302+/-14, respectively, P<0.05). HDL was higher in black men than white men, and triglycerides were higher in white men than black men. Cholesterol was similar across all groups, but BMI was highest in white men with CaP. We also found a significant association between BMI and pathological stage of prostate cancer patients among both black and white men (P<0.05). Our study demonstrated that black men who developed CaP had higher serum testosterone levels, on average, than white men who developed CaP. Furthermore, BMI was highest in white men developing CaP compared to black men, but we found a significant association between pathological stage and BMI in both black and white patients. Although it is controversial whether obesity is considered to be a risk factor for prostate cancer, this small pilot study suggests that BMI may play a role in the progression of the disease once it is established.Prostate Cancer and Prostatic Diseases (2001) 4, 101-105
Prostate Cancer Prostatic Dis 2001
PMID:A pilot study analyzing PSA, serum testosterone, lipid profile, body mass index and race in a small sample of patients with and without carcinoma of the prostate. 1249 46

Cholesterol is a neutral lipid that accumulates in liquid-ordered, detergent-resistant membrane domains called lipid rafts. Lipid rafts serve as membrane platforms for signal transduction mechanisms that mediate cell growth, survival, and a variety of other processes relevant to cancer. A number of studies, going back many years, demonstrate that cholesterol accumulates in solid tumors and that cholesterol homeostasis breaks down in the prostate with aging and with the transition to the malignant state. This review summarizes the established links between cholesterol and prostate cancer (PCa), with a focus on how accumulation of cholesterol within the lipid raft component of the plasma membrane may stimulate signaling pathways that promote progression to hormone refractory disease. We propose that increases in cholesterol in prostate tumor cell membranes, resulting from increases in circulating levels or from dysregulation of endogenous synthesis, results in the coalescence of raft domains. This would have the effect of sequestering positive regulators of oncogenic signaling within rafts, while maintaining negative regulators in the liquid-disordered membrane fraction. This approach toward examining the function of lipid rafts in prostate cancer cells may provide insight into the role of circulating cholesterol in malignant growth and on the potential relationship between diet and aggressive disease. Large-scale characterization of proteins that localize to cholesterol-rich domains may help unveil signaling networks and pathways that will lead to identification of new biomarkers for disease progression and potentially to novel targets for therapeutic intervention.
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PMID:Cholesterol and prostate cancer. 1468 82


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