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)

The recent removal of refecoxib (a cyclo-oxygenase II inhibitor), a drug involved in a large prostate cancer chemoprevention trial, and the completion of recruitment for the SELECT cancer chemoprevention trial utilizing selenium and vitamin E should lead researchers to ponder a similar question in cancer chemoprevention. The question of "What agent should be utilized and what clinical trial should designed and conducted next for cancer chemoprevention?" Part I and II of this manuscript attempts to argue that statins or cholesterol-lowering drugs or heart healthy agents are the ideal next choice for a large chemoprevention trial for numerous reasons including: (1) Cardiovascular disease (CVD) has been the number one cause of death in men and women every year in the US since 1900; (2) CVD has been the number one cause of death in the major cancer chemoprevention trials; (3) CVD has been the number one or two cause of death of men and women postdiagnosis of breast, colorectal, and prostate cancer; and (4) the recent potential relationship between certain cancers and dyslipidemia needs to be investigated. What other chemoprevention agent can also boast that in the worst case scenario the number one cause of death in men and women would probably be reduced in this future cancer chemoprevention trial of statins?! The list continues to grow of cancer chemoprevention trials that will probably be either a complete hit or miss. In other words, they will or have reduced the disease of interest with virtually no potential role for reducing the number one cause of death in men and women. The time seems more than overdue for a statin and/or another cholesterol lowering or heart healthy cancer chemoprevention trial.
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PMID:Why a statin and/or another proven heart healthy agent should be utilized in the next major cancer chemoprevention trial: part II. 1561 Aug 64

Although the avocado is known as a rich source of monounsaturated fatty acids, there has been far less attention given to its content of other bioactive substances including carotenoids, which might contribute to cancer preventive properties similar to those attributed to other fruits and vegetables. The yellow-green color of the avocado prompted us to study the carotenoid content of this fruit using established methods in our laboratory. The California Hass avocado (Persea americana Mill.) was selected for study, because it is the most commonly consumed variety in the southwest United States. These avocados were found to contain the highest content of lutein among commonly eaten fruits as well as measurable amounts of related carotenoids (zeaxanthin, alpha-carotene, and beta-carotene). Lutein accounted for 70% of the measured carotenoids, and the avocado also contained significant quantities of vitamin E. An acetone extract of avocado containing these carotenoids and tocopherols was shown to inhibit the growth of both androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines in vitro. Incubation of PC-3 cells with the avocado extract led to G(2)/M cell cycle arrest accompanied by an increase in p27 protein expression. Lutein alone did not reproduce the effects of the avocado extract on cancer cell proliferation. In common with other colorful fruits and vegetables, the avocado contains numerous bioactive carotenoids. Because the avocado also contains a significant amount of monounsaturated fat, these bioactive carotenoids are likely to be absorbed into the bloodstream, where in combination with other diet-derived phytochemicals they may contribute to the significant cancer risk reduction associated with a diet of fruits and vegetables.
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PMID:Inhibition of prostate cancer cell growth by an avocado extract: role of lipid-soluble bioactive substances. 1562 37

Prostate cancer continues to be a major health threat, especially among African American men. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), which opened on July 25, 2001, was planned to study possible agents for the prevention of prostate cancer in a population of 32,400 men in the United States, including Puerto Rico, and Canada. SELECT is a phase III randomized, placebo-controlled trial of selenium (200 microg/day from L-selenomethionine) and/or vitamin E (400 IU/day of all rac alpha-tocopheryl acetate) supplementation for a minimum of 7 years (maximum of 12 years) in non-African American men at least 55 years of age and African American men at least 50 years of age. SELECT is a large, simple trial that conforms as closely as possible with community standards of care. This commentary discusses the design problems the SELECT investigators had to resolve in developing the trial, including the role of prostate cancer screening, the best forms and doses of the study agents, and estimation of the event (prostate cancer) rate of men on the placebo arm.
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PMID:Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). 1565 39

The prostate has only one function, namely to secrete fluid containing substances that are needed for reproduction. This requires an extremely high concentration of androgens in the tissues. Benign prostatic hypertrophy (BPH) seems to be related to the long-term exposure of the prostate to the strong androgen 5alpha-dihydrotestosterone (DHT) and, possibly, to estrogens. The relation between prostate cancer and androgens is suggested to be U-shaped, with both extremes of androgen concentrations being associated with increased risk of invasive cancer. In the treatment of patients with BPH, the lipidic liposterolic extracts of Serenoa repens were as effective as the pharmaceutical inhibitors of the 5alpha-reductase enzyme or alpha1-adrenergic blockers in relieving urinary symptoms. In addition to moderately inhibiting the 5alpha-reductase activity, Serenoa seems to exert anti-inflammatory and complementary cellular actions with beneficial effects on the prostate. Unlike the pharmaceutical 5alpha-reductase inhibitors, finasteride and dutasteride, Serenoa does not suppress serum PSA, facilitating the follow-up and the early detection of prostate cancer. We suggest a strategy to prevent prostate cancer that aims at providing men with partial androgen deficiency correct testosterone substitution with a sustained release buccal bio-adhesive tablet. In addition, food supplementation with extracts of Serenoa repens and a combination of the antioxidants selenium, (cis)-lycopene and natural vitamin E, together with fish oil rich in long-chain polyunsaturated essential fatty acids of the omega-3 group seems warranted. Clearly, a holistic approach including careful clinical and biological monitoring of the aging man and his prostate remains mandatory.
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PMID:Preventing diseases of the prostate in the elderly using hormones and nutriceuticals. 1567 40

There are no established risk factors for prostate cancer other than age, ethnic group, and family history. For dietary factors, the WCRF/AICR reported that diets high in vegetables were possibly protective, and that regular consumption of red meat, fat, saturated/animal fat, and milk and any products possibly increased risk. Among nutritional factors, a protective effect of lycopene, vitamin E, selenium, and perhaps fish oil and phytoestrogens appear particularly promising, although no definite answers have yet emerged. Although hormonal influences are biologically plausible, observational studies of androgen have not produced consistent results. While, insulin-like growth factor 1 could be a risk factor. Based on these evidences, several chemoprevention trials were launched using 5-alpha reductase inhibitor, selenium, vitamin E and so on.
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PMID:[Risk factors and current chemoprevention studies in prostate cancer]. 1571 86

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated a 32% reduction in prostate cancer incidence in response to daily alpha-tocopherol supplementation. We examined baseline serum concentrations of alpha-tocopherol and gamma-tocopherol to compare their respective associations with prostate cancer risk. From the ATBC Study cohort of 29 133 Finnish men, 50-69 years old, we randomly selected 100 incident prostate cancer case patients and matched 200 control subjects. Odds ratios and 95% confidence intervals (CIs) were estimated for the serum tocopherols (measured by high-performance liquid chromatography) using logistic regression models. All P values were two-sided. Odds ratios for the highest versus the lowest tertiles were 0.49 (95% CI = 0.24 to 1.01, P(trend) = .05) for alpha-tocopherol and 0.57 (95% CI = 0.31 to 1.06, P(trend) = .08) for gamma-tocopherol. Further analyses indicated that the association of high serum tocopherols with low prostate cancer risk was stronger in the alpha-tocopherol-supplemented group than in those not receiving alpha-tocopherol. Participants with higher circulating concentrations of the major vitamin E fractions, alpha-tocopherol and gamma-tocopherol, had similarly lower prostate cancer risk.
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PMID:Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. 1574 76

Preclinical, epidemiological, and phase III data from randomized, placebo-controlled clinical trials suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. In vitro evidence suggests that selenium and vitamin E work synergistically to cause cell-cycle arrest, induce caspase-mediated apoptosis, and act as antiandrogens in arresting clonal expansion of nascent tumors. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), sponsored by the National Cancer Institute, is an intergroup Phase III, randomized, double-blind, placebo-controlled, population-based clinical trial designed to test the efficacy of selenium and vitamin E alone and in combination in the prevention of prostate cancer. The study has a 2 x 2 factorial design with a target accrual of 32,400. Eligibility criteria include an age of at least 50 years for African Americans and of at least 55 years for Caucasians; a DRE not suspicious for cancer; a serum PSA no greater than 4 ng/mL; and a normal blood pressure. Randomization will be equally distributed among the four study arms, with intervention consisting of a daily oral dose of study supplement (200 mug l-selenomethionine or 400 mg of racemic alpha-tocopheryl) or matched placebo. Study duration is planned for 12 years, with a 5-year uniform accrual period and a minimum of 7 and maximum of 12 years of intervention. The primary endpoint for SELECT is the clinical incidence of prostate cancer as determined by a recommended routine clinical diagnostic work-up, including yearly DRE and serum PSA level. SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001, with final results anticipated in 2013.
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PMID:Selenium and vitamin E cancer prevention trial. 1575 49

In this study, we evaluated the antiproliferative effect of tocotrienols (T3) and the presence of a specific vitamin E metabolism in PC3 and LNCaP prostate cancer cells. These cell lines are able to transform tocopherols (T) and T3 in the corresponding carboxyethyl-hydroxychromans metabolites (CEHCs). The extent of this metabolism and the inhibitory effect on cell growth followed the order of magnitude alpha-T<alpha-T3<gamma-T<gamma-T3. The partial inhibition of gamma-T3 metabolism by ketoconazole did not influence cell proliferation. These early findings may suggest that the transformation of vitamin E to CEHC is mostly a detoxification mechanism useful to maintain the malignant properties of prostate cancer cells.
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PMID:Gamma-tocotrienol metabolism and antiproliferative effect in prostate cancer cells. 1575 78

Prostate cancer, the most frequent cancer in men over the age of 50, appears to be associated with certain nutritional risk factors. The role of these factors is revealed by epidemiological data (variation of prostate cancer incidence according to various regions of the world, modification of these incidences in relation to migratory flows of certain populations) and eating habit studies. These findings are the basis for a number of studies designed to determine the ideal diet to prevent and, if possible, contribute to the treatment of prostate cancer. The fat intake, the type of fat, the absorption of vitamins, trace elements, antioxidants (beta-carotene, lycopene), phyto-oestrogens, including soybean or plant mixtures such as PC-SPES, may all constitute nutritional factors involved in prostatic carcinogenesis. However, although a review of the literature shows that some populations appear to be more effectively protected than others by their cultural consumption of particular substances, the link with efficacy, in terms of prevention, of a diet based on this substance administered to another population has yet to be demonstrated. Although the ideal diet is unknown at the present time, some of these ingredients appear to be good candidates, such as unsaturated fats, soybean proteins, carotenoids, lycopene and vitamin E.
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PMID:[Diet and prostate cancer: from prevention to treatment]. 1577 17

Randomized trials have shown, unexpectedly, that supplementation with selenium or vitamin E is associated with a reduction of prostate cancer risk. We assess whether a supplementation with low doses of antioxidant vitamins and minerals could reduce the occurrence of prostate cancer and influence biochemical markers. The SU.VI.MAX trial comprised 5,141 men randomized to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years. Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrollment and at the end of follow-up from 3,616 men. Cox regression models were used to estimate the hazard ratio and related 95% confidence interval of prostate cancer associated with the supplementation and to examine whether the effect differed among predetermined susceptible subgroups. During the follow-up, 103 cases of prostate cancer were diagnosed. Overall, there was a moderate nonsignificant reduction in prostate cancer rate associated with the supplementation (hazard ratio = 0.88; 95% CI = 0.60-1.29). However, the effect differed significantly between men with normal baseline PSA (< 3 microg/L) and those with elevated PSA (p = 0.009). Among men with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements (hazard ratio = 0.52; 95% CI = 0.29-0.92). In men with elevated PSA at baseline, the supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (hazard ratio = 1.54; 95% CI = 0.87-2.72). The supplementation had no effect on PSA or IGF levels. Our findings support the hypothesis that chemoprevention of prostate cancer can be achieved with nutritional doses of antioxidant vitamins and minerals.
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PMID:Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. 1580 Sep 22


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