A Nutrient Approach to Prostate Cancer Prevention: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. Nutrition and Cancer
(Impact Factor: 2.32).
10/2010; 62(7):896-918. DOI: 10.1080/01635581.2010.509833
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomized 35,533 healthy men, >55 yr old (>50 yr if African American), with normal digital rectal exams and prostate specific antigens <4 ng/ml to 1) 200 μg/day l-selenomethionine, 2) 400 IU/day all-rac-alpha-tocopheryl acetate (vitamin E), 3) both supplements, or 4) placebo for 7 to 12 yr. The hypotheses underlying SELECT, that selenium and vitamin E individually and together decrease prostate cancer incidence, derived from epidemiologic and laboratory evidence and significant secondary endpoints in the Nutritional Prevention of Cancer (selenium) and Alpha-Tocopherol Beta-Carotene (vitamin E) trials. In SELECT, prostate cancer incidence did not differ among the 4 arms: hazard ratios [99% confidence intervals (CIs)] for prostate cancer were 1.13 (99% CI = 0.95-1.35, P = 0.06; n = 473) for vitamin E, 1.04 (99% CI = 0.87-1.24, P = 0.62; n = 432) for selenium, and 1.05 (99% CI = 0.88-1.25, P = 0.52; n = 437) for selenium + vitamin E vs. 1.00 (n = 416) for placebo. Statistically nonsignificant increased risks of prostate cancer with vitamin E alone [relative risk (RR) = 1.13, P = 0.06) and newly diagnosed Type 2 diabetes mellitus with selenium alone (RR = 1.07, P = 0.16) were observed. SELECT data show that neither selenium nor vitamin E, alone or together, in the doses and formulations used, prevented prostate cancer in this heterogeneous population of healthy men.
Available from: Carmen Sanmartín
- "In spite of the evidence outlined above, there is some controversy related to the hypotheses that Se and other compounds, such as Vitamin E, decrease PC incidence either individually or in combination. For example, Dunn et al.  reported that neither Se nor Vitamin E (SELECT), alone or together, prevented PC in a study carried out on a heterogeneous population of healthy men. Stratton et al.  also observed that Se supplementation to 140 men distributed into a placebo group and two groups that received different amounts of Se did not show a protective effect in subjects with localized PC. "
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ABSTRACT: According to World Health Organization, neglected tropical diseases encompass all diseases that occur solely, or principally, in the tropics. In practice, the term is often taken to refer to infectious diseases that thrive in hot, humid conditions. Clinical and epidemiological studies suggest that selenium (Se) play an important role in tropical diseases, such as tuberculosis, leishmaniasis, filariasis and chagas, acting as preventive agent or in diagnosis and prognosis. Recent studies have evinced the importance of selenium in oxidative status and antioxidant defense capabilities during the course of infection and progression of the illness in human patients and experimental models. For this reason, one of the most relevant mechanism of action proposed involve selenoproteins, i.e. glutathione peroxidase (GPx), an enzyme that protects against oxidative stress and modulates the redox processes. In addition, it was observed that low Se levels were positively correlated with an increased susceptibility to infections. Besides, Se supplementation is proposed as an adjuvant therapy for treatment of these chronic diseases. However, there is a lack in the literature references related to synthesis and biological evaluation of novel derivatives containing selenium moiety against these diseases. During the last years our research group is interested in the design and synthesis of organoselenium compounds as new class of agents for treatment of neglected tropical diseases. In the present year we have reported two general structures with leishmanicidal activity, corresponding both of them to symmetrical compounds. The firsts are alkyl imidoselenocarbamates (alkyl isoselenourea) which possessed a moderate effect in vitro and the second ones are selenocyanates and diselenides. It is remarkable that some of them showed stronger in vitro antileishmanial activity than edelfosine and miltefosine, used as reference drugs, and combined high potency and low cytotoxicity against Jurkat and THP-1 cells.
Selenium: Sources, Functions and Health Effects, Edited by Chinatsu Aomori, Megumi Hokkaido, 08/2012: chapter 7: pages 163-179; Nova Publishers., ISBN: 978−1−61942−061−8
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ABSTRACT: The understanding of the essential role of selenium (Se) in human health has increased substantially in recent decades. Micronutrient deficiencies are very common in the general population and may be even more common in patients with different pathologies due to genetic or environmental causes and prescription drug use. Selenium is used by people in the prevention and/or treatment of different disorders including cardiovascular disease, osteoarthritis, rheumatoid arthritis, hypothyroidism, stroke, atherosclerosis, cancer susceptibility and treatment, HIV, AIDS, neuronal diseases such as Alzheimer or amyotrophic lateral sclerosis, pancreatitis, depression, and diabetes amongst others. Several mechanisms have been suggested to mediate the biological effects of Se and these include antioxidant defence systems, synthesis and stability of metabolites that act as intermediates implicated in diverse selenoproteins expression pathways oxidative metabolism, immune system modulation, DNA intercalators, kinase regulation, enzymatic cofactor, and gene expression. A number of clinical trials in recent years have provided convincing evidence of the central role of this element, either alone or in combination with other micronutrients or antioxidants, in the prevention and treatment of multiple diseases. Based on these studies this review focuses on the advances made so far in the study of mechanisms and applications of selenium compounds that could be suitable for chronic diseases.
Current Medicinal Chemistry 08/2011; 18(30):4635-50. DOI:10.2174/092986711797379249 · 3.85 Impact Factor
Available from: Laura M Beaver
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ABSTRACT: The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.
Advances in Nutrition 11/2011; 2(6):497-510. DOI:10.3945/an.111.001032 · 4.71 Impact Factor
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