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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is the commonest non-skin malignancy in the United States and has a substantial mortality rate despite the use of PSA-based screening. Furthermore, therapy for prostate cancer by surgery, radiotherapy or hormonal manipulation carries a significant risk of treatment-related morbidity. Recent analysis of secondary endpoints of several large-scale randomized prospective clinical trials for other malignancies has suggested that selenium or vitamin E may result in a decreased incidence and mortality from prostate cancer. In vitro and preclinical studies of these antioxidants support this hypothesis. This review outlines the rationale and design of SELECT, the Selenium and Vitamin E Cancer Prevention Trial, designed to test the hypothesis that selenium or vitamin E alone or in combination can reduce the clinical incidence of prostate cancer in a population-based cohort of men at risk. SELECT is a phase III, randomized, double-blinded, prospective, 2x2 factorial clinical trial which will randomize 32,400 healthy men with normal DRE and serum PSA to one of four study arms: selenium alone, vitamin E alone, selenium+vitamin E, or placebo. Study agents will be taken orally for a minimum of 7 and maximum of 12 y with assessments of general health, incident prostate cancer and toxicity performed at 12 month intervals. Under the assumptions described, the detectable risk reduction is 25% for an effective single agent relative to placebo, with an additional 25% reduction for the combination relative to an effective single agent. The estimated power for the comparison of a single agent vs placebo is 96% and the power for the comparison of an effective single agent vs combination is 89%. Secondary endpoints will include prostate cancer-free survival, all-cause mortality, and the incidence and mortality of other cancers and diseases potentially impacted by the chronic use of selenium and vitamin E. Other trial objectives will include periodic quality of life assessments, assessment of serum micronutrient levels and prostate cancer risk, and studies of the evaluation of biological and genetic markers with the risk of prostate cancer. Prostate Cancer and Prostatic Diseases (2000) 3, 145-151
Prostate Cancer Prostatic Dis 2000 Nov
PMID:SELECT: the Selenium and Vitamin E Cancer Prevention Trial: rationale and design. 1249 90

Increased intake of vitamin E has been suggested to be protective against prostate cancer in men, but the effects of vitamin E on prostate growth and function remain poorly defined. The purpose of this study was to determine the effects of vitamin E deficiency on pubertal growth and maturation of the prostate in the rat. Animals were placed on a vitamin E deficient diet at 28 days of age and were followed for 15 and 26 weeks. Vitamin E deficient rats had a circulating vitamin E level of less than 1% of control animals and experienced a decrease in body and testis weight. The deficiency did not alter the weights of the ventral and dorsal lobes of the prostate. However, there was an increase in weight, DNA, and protein contents of the lateral lobe in control and vitamin E deficient rats from 15 to 26 weeks of treatment, but these increases were significantly lower in vitamin E deficient 26-week treated rats. The volume of secretion per milligram tissue was greater in the ventral than lateral or dorsal lobes. The volume of secretion and activity of the secretory 26 kDa protease in the ventral prostate was lower in vitamin E deficient rats at 15 weeks, but not at 26 weeks of treatment. In contrast, the relative protein content of lateral lobe secretion increased in both control and vitamin E deficient rats from 15 to 26 weeks of treatment. The lateral, but not ventral or dorsal, lobes of both control and vitamin E deficient rats were affected by chronic prostatitis as evidenced by infiltration of inflammatory cells. The lateral lobes also showed markedly elevated activities of the matrix metalloproteinases gelatinase A (MMP-2) and gelatinase B (MMP-9). These data indicate that vitamin E deficiency does not alter the growth of the prostatic lobes, nor the onset and extent of lateral lobe specific prostatitis, but it may delay some differentiated functions such as secretion of specific proteins in the ventral lobe. Thus, the effects of vitamin E in the prostate of the rat appear to be selective.
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PMID:Effect of vitamin E deficiency on the growth and secretory function of the rat prostatic complex. 1278 14

Target populations for chemoprevention trials should include those at higher than average risk for the development of prostate cancer as defined by explicit epidemiologic and genetic criteria. Such populations include a "primary prevention" group without histologic or clinical evidence of cancer, and several clinical models of "secondary prevention," including those with clinically evident disease prior to definitive therapy and those at high risk of recurrence after therapy based on histology and/or biochemical status. Each risk group and clinical model has potential advantages and disadvantages, and the mechanisms which underlie disease development and progression in each group may be unique. These observations give rise to many potential clinical trials of specific agents. These trials should also include collection of data on potentially confounding influences on disease development and progression. Preclinical, epidemiologic, and Phase II data suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. The experience of the Prostate Cancer Prevention Trial (PCPT) demonstrates the interest and dedication of healthy men to long-term studies of cancer prevention. SELECT, the Selenium and Vitamin E Cancer Prevention Trial, 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 which builds on secondary analyses of large-scale chemoprevention trials for other cancers and the lessons of PCPT.
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PMID:Clinical models for testing chemopreventative agents in prostate cancer and overview of SELECT: the Selenium and Vitamin E Cancer Prevention Trial. 1290 56

The ongoing Selenium and Vitamin E Chemoprevention Trial is designed to evaluate the efficacy of these two agents, either individually or in combination, in reducing the incidence of prostate cancer in healthy men over 55 years of age. Little information, however, is available on the potential synergy between vitamin E and selenium in chemoprevention. The present study was aimed at addressing this gap of knowledge with the use of the androgen-unresponsive, p53-null, PC-3 human prostate cancer cell line. The growth-inhibitory activity of vitamin E appeared to be dependent on the chemical form. In our hands, D-alpha-tocopheryl succinate (VES) was much more potent than either DL-alpha-tocopherol or D-alpha-tocopheryl acetate. Combining VES with methylseleninic acid (MSA), a selenium metabolite, produced a synergistic effect on cell growth suppression. The synergy was accounted for primarily by an augmented apoptotic response. Poly(ADP-ribose) polymerase cleavage and activation of specific caspases were confirmed by Western blot analysis. The caspases that were commonly modulated by either VES or MSA included initiator caspases-8 and -10, as well as executioner caspases-3, -6, and -7. In contrast, caspase-9 was activated only by VES, whereas caspases-1 and -12 were activated only by MSA. Based on the above information, it is proposed that the mitochondrial pathway and the endoplasmic reticulum stress/cytokine signaling pathway might be involved in apoptosis induction by VES and MSA, respectively. These two pathways may act in a cooperative manner to switch on the full force of the apoptotic machinery when cells are treated with both VES and MSA.
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PMID:Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. 1458 1

The lignan enterolactone, produced by the intestinal microflora from dietary precursors, has been hypothesized to protect against hormone-dependent cancers and cardiovascular diseases. We conducted a nested case-control study to examine the relationship between serum enterolactone concentration and prostate cancer. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum collected at baseline in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study from 214 men with prostate cancer diagnosed during a 6-year follow-up and from 214 controls matched by age, date of baseline blood collection, intervention group, and local study area. Mean serum enterolactone concentration (in nmol/liter) did not differ significantly between case and control subjects [15.9 (SD, 15.2) versus 16.9 (SD, 14.9), respectively (P = 0.42)]. Odds ratios for prostate cancer risk estimated by conditional logistic regression for increasing quartiles of enterolactone concentration were 1.00 (referent), 0.72 [95% confidence interval (CI), 0.43-1.23], 0.98 (95% CI, 0.58-1.68), and 0.71 (95% CI, 0.42-1.21). Our findings do not support the hypothesis that enterolactone is involved in the development of prostate cancer.
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PMID:Serum enterolactone concentration is not associated with prostate cancer risk in a nested case-control study. 1465 83

The National Cancer Institute in cooperation with the Southwest Oncology Group has begun one of the largest prostate cancer prevention studies to date, the Selenium and Vitamin E Chemoprevention Trial (SELECT). The purpose of this article is to review the evidence and discuss the individual antioxidant compounds under study. The authors comprehensively reviewed the peer-reviewed literature on the chemoprevention of prostate cancer with emphasis on the antioxidants vitamin E and selenium. The credible leads for the primary prevention of prostate cancer using selenium and vitamin E have emerged as secondary findings from randomized controlled trials with corroborative evidence from observational and in vitro studies. Selenium and vitamin E are widely available compounds that are safe if taken in moderation, with relatively few adverse effects. The evidence in support of the antioxidants in the primary prevention of prostate cancer is promising, and the next step in definitively answering the question has been addressed by the investigators of SELECT. The SELECT study will define the role of the antioxidants selenium and vitamin E in the prevention of prostate cancer; complete data from the study will be available in 12 years.
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PMID:Review of vitamin E and selenium in the prevention of prostate cancer: implications of the selenium and vitamin E chemoprevention trial. 1466 28

There is some evidence that alpha-linolenic acid might be positively related to prostate cancer risk. Associations between serum fatty acid composition as well as fatty acid intakes and prostate cancer risk were examined in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort included 29,133 male smokers aged 50-69 years. During 5-8 years of follow-up, 246 prostate cancer cases were diagnosed. One control was selected and matched by age (+/- 1 month) for each case from the cohort subjects alive and free of prostate cancer at the time the case was diagnosed. This study included 198 case-control pairs with baseline serum sample available for both. Fatty acids of serum cholesterol esters were measured as a percentage of total fatty acids, using capillary gas chromatography. Intakes of fatty acids were assessed from a validated self-administered dietary questionnaire. Serum and dietary fatty acids had no consistent association with prostate cancer risk. Serum alpha-linolenic acid was not related to prostate cancer risk. Twofold risk was found in the highest quartile of serum myristic acid compared with the lowest quartile (odds ratio, 1.93; 95% confidence interval, 1.02-3.64). alpha-Tocopherol supplementation modified the association between serum linoleic acid and prostate cancer risk (P for interaction 0.03); odds ratio was 0.17 (95% confidence interval, 0.04-0.68) in the highest quartile of serum linoleic acid compared with the lowest quartile in men who received alpha-tocopherol, whereas no association was found in men who did not receive alpha-tocopherol. In conclusion, we found no overall association between serum or dietary alpha-linolenic acid or any other unsaturated fatty acid and prostate cancer risk, but high serum linoleic acid was associated with lower risk in men supplemented with alpha-tocopherol. High serum myristic acid associated with an increased risk of prostate cancer.
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PMID:Fatty acids and risk of prostate cancer in a nested case-control study in male smokers. 1469 32

Vitamin E and selenium are the two most popular dietary supplements used to prevent prostate cancer. The hypothesis that these antioxidants reduce prostate risk is being tested in the selenium and vitamin E chemoprevention trial (SELECT). We hypothesize that selenium potentiates vitamin E-induced inhibition of prostate cancer cell growth in vitro. Prostate cancer cell populations growing asynchronously were treated with a combination of vitamin E and selenium and processed for flow cytometric analysis. Prostate cancer cells treated with a combination of the antioxidants revealed that selenium potentiates vitamin E-induced inhibition of LNCaP cells in vitro. This was demonstrated by a reduction in the percentage of cells in the S phase. This crucial finding confirms our previous observations that antioxidant molecules act via distinct mechanistic pathways. These independent biological effects can be exploited in order to augment the anticancer properties of individual agents. These data also validate the two factorial design of the SELECT trial, permitting pairwise comparisons between agents in combination and alone.
Prostate Cancer Prostatic Dis 2004
PMID:Synergistic effect of vitamin E and selenium in human prostate cancer cell lines. 1474 39

It is known that gamma-tocopherol inhibits human prostate cancer cell proliferation via down-regulation of cyclin-related signalling but tocopherol and tocotrienol metabolites with a shortened phytyl chain, carboxyethyl hydroxychromans, were not previously investigated as anti-proliferative agents. In this study, the effect of the two main tocopherols, namely, alpha-tocopherol and gamma-tocopherol, and their corresponding metabolites (alpha- and gamma-carboxyethyl hydroxychromans) was studied on proliferation and cyclin D1 expression of the prostate cancer cell line PC-3. The hydrosoluble vitamin E analogues Trolox and alpha-tocopherol succinate were also tested. The most effective inhibitors of PC-3 proliferation were gamma-tocopherol and gamma-carboxyethyl hydroxychroman. Their effect was discernable at 1 microM and reached a plateau at concentrations > or = 10 microM with maximal inhibition values ranging between 70 and 82%. alpha-Tocopherol, alpha-carboxyethyl hydroxychroman, and the analogue Trolox were much less effective; a weak effect was observed for concentrations < or = 10 microM and a maximal inhibition of less than 45% was found at 50 microM concentration. PC-3 cells showed higher inhibition, particularly by the gamma derivatives, than HTB-82 and HECV cells. Tocopherols and carboxyethyl hydroxychromans exerted an inhibitory effect on cyclin D1 expression parallel to the retardation of cell growth. gamma-Carboxyethyl hydroxychroman and gamma-tocopherol showed effects also upstream of the cyclin modulation. Furthermore, the inhibition of cyclin D1 expression by gamma-carboxyethyl hydroxychroman was competed for by alpha-carboxyethyl hydroxychroman. In conclusion, this study shows that carboxyethyl hydroxychroman metabolites are as effective as their vitamin precursors to inhibit PC-3 growth by specific down-regulation of cyclin expression, with the gamma forms being the most effective ones. Although the inhibition of PC-3 cell growth and diminution of cyclin expression are clearly visible, more subtle mechanistic effects of tocopherols and their corresponding carboxyethyl hydroxychroman metabolites deserve further investigations.
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PMID:The effect of alpha- and gamma-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation. 1487 72

Epidemiological studies, preclinical investigations and clinical intervention trials support the role of selenium compounds as potent cancer chemopreventive agents; the dose and the form of selenium are critical factors in cancer prevention. Induction of apoptosis and inhibition of cell proliferation are considered important cellular events that can account for the cancer preventive effects of selenium. Toxicity should always be considered a determining factor in the selection of potential chemopreventive agents. Prior to induction of apoptosis, selenium compounds alter the expression and/or activities of a number of cell cycle regulatory proteins, signaling molecules, proteases, mitochondrial associated factors, transcriptional factors, tumor suppressor genes, polyamine and glutathione levels. Depending on the form, selenium compounds can target separate pathways but more efforts are needed to learn about disrupting different pathways converging to apoptosis. Numerous selenium compounds are known to inhibit carcinogenesis in several animal models but not all of these have been examined for their efficacy to induce apoptosis or vice versa in the corresponding target organ. Studies aimed at investigating the effects of selenium compounds on apoptosis in the target organ in vivo and in vitro are limited. On the basis of information provided in this review, we recommend that additional molecular markers should be added to those proposed in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) on prostate cancer. Apart from the selenium compounds reviewed here, several novel synthetic organoselenium compounds need to be examined both in vitro and in vivo for their potential to induce apoptosis; such an investigation may provide better and mechanism-based cancer chemoprevention as well as chemotherapeutic agents.
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PMID:Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds. 1496 64


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