Phase III prostate cancer prevention trials: are the costs justified?
ABSTRACT One randomized, prospective clinical trial for chemoprevention of prostate cancer has been completed, and two additional trials are ongoing. The investment, time, and effort for these trials are substantial. We reviewed the outcomes of these trials to address the value of the investment. The outcomes of the Prostate Cancer Prevention Trial (testing finasteride) and the design of the Selenium and Vitamin E Cancer Prevention Trial (SELECT; testing vitamin E and selenium) trial as well as the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial (testing dutasteride) were reviewed. From a public health standpoint, there is tremendous potential for benefit from large-scale cancer prevention trials. Because of the volume of data that are collected, potential discoveries related to the biology of the disease are substantial. Translational scientific efforts are direct outgrowths of these studies. Prospective, randomized chemoprevention trials for prostate and other cancers are expensive and require long periods of time to conduct, yet the rewards are on a par with the investment.
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ABSTRACT: Selenium (Se) is an important micronutrient that, as a component of selenoproteins, influences oxidative and inflammatory processes. Its' levels vary considerably, with different ethnic and geographic population groups showing varied conditions, ranging from frank Se deficiencies to toxic effects. An optimum Se level is essential for the maintenance of homeostasis, and this optimum may vary according to life stage, general state of health, and genotype. Nutrigenetic studies of different Se levels, in the presence of genetic variants in selenoproteins, suggest that an effective dietary Se intake for one individual may be very different from that for others. However, we are just starting to learn the significance of various genes in selenoprotein pathways, functional variants in these, and how to combine such data from genes into pathways, alongside dietary intake or serum levels of Se. Advances in systems biology, genetics, and genomics technologies, including genetic/genomic, epigenetic/epigenomic, transcriptomic, proteomic, and metabolomic information, start to make it feasible to assess a comprehensive spectrum of the biological activity of Se. Such nutrigenomic approaches may prove very sensitive biomarkers of optimal Se status at the individual or population level. The premature cessation of a major human Se intervention trial has led to considerable controversy as to the value of Se supplementation at the population level. New websites provide convenient links to current information on methodologies available for nutrigenetics and nutrigenomics. These new technologies will increasingly become an essential tool in optimizing the level of Se and other micronutrients for optimal health, in individuals and in population groups. However, definitive proof of such effects will require very large collaborative studies, international agreement on study design, and innovative approaches to data analysis.Frontiers in Genetics 01/2011; 2:15.
Chapter: Prostatakarzinom[Show abstract] [Hide abstract]
ABSTRACT: Über die vergangenen Jahrzehnte hat sich das Prostatakarzinom (PCA), trotz auffälliger Diskrepanz in der Inzidenz, über ethnische Grenzen hinweg weltweit zu einem der dominierenden Malignome des Mannes entwickelt. Sowohl in den Hoch- wie auch in Niedrigrisikopopulationen der Welt stieg bzw. steigt die Inzidenz deutlich an, eine Tendenz, die sich durch die zunehmende Lebenserwartung noch fortsetzen dürfte .12/2008: pages 485-635;
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ABSTRACT: Maslinic acid is found in various natural sources, most notably in pomace olive oil, and exerts pro-apoptotic activities in various cancer cells in vitro. In the present study, DU145 human prostate cancer cells were cultured with 0-25 μm-maslinic acid to examine the effects of maslinic acid on the metastatic capacity of prostate cancer cells. Maslinic acid significantly (P < 0·05) inhibited the basal and epidermal growth factor (EGF)-induced migration (27-64 %), invasion (23-60 %) and adhesion (8-40 %) of DU145 cells. Maslinic acid significantly (P < 0·05) down-regulated both basal and EGF-stimulated secretion of matrix metalloproteinase (MMP)-9 (25-67 %), MMP-2 (50-86 %), urokinase-type plasminogen activator (uPA, about 100 %), vascular endothelial growth factor (VEGF, 98-100 %) and tissue inhibitors of metalloproteinases (TIMP)-1, as well as expression of uPA receptor (uPAR), intercellular adhesion molecules (22-33 %), vascular cell adhesion molecules (23-46 %) and E-cadherin, whereas it increased TIMP-2 secretion. Maslinic acid dramatically reduced the levels of hypoxia-inducible factor-1α (HIF-1α) protein and mRNA; the reduction was accompanied by reduced stability, nuclear levels and transcriptional activity of HIF-1α. The levels of phospho-Akt and phospho-extracellular signal-related kinase (ERK) were reduced in cells treated with maslinic acid, and the phosphoinositide 3-kinase inhibitor LY294002 and the mitogen-activated protein kinase kinase inhibitor PD98059 reduced HIF-1α levels and VEGF secretion. The results show that maslinic acid markedly inhibited the migration, invasion and adhesion of DU145 prostate cancer cells. Suppressing HIF-1α activation by inhibiting Akt and ERK activation may be part of the mechanism by which maslinic acid inhibited uPAR, E-cadherin, VEGF and MMP expression in DU145 cells.The British journal of nutrition 04/2012; · 3.45 Impact Factor