Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to the major geographical variations affecting its clinical incidence, prostate cancer appears to be influenced by environmental factors, which may either promote or inhibit the development of this tumour. Diet appears to play a considerable role among these environmental factors. There are epidemiological and experimental arguments in favour of the role of diet in the development of prostatic cancer. Certain foods, such as fats, phenolic compound and other micronutrients such as vitamins or selenium have been reported to have an action on the natural history of prostate cancer. The authors present a review of the literature analysing the various potential actions of various foods.
 ...
PMID:[Nutrition and prostatic cancer]. 1106 88

The approach to clinical medicine has evolved over the last 20 years to incorporate therapeutic strategies to prevent long-term negative outcomes rather than simply treat acute events. As a result, new treatment paradigms have been developed in various disease areas. These paradigms arise from clinical trials that show a correlation between risk reduction and decreases in painful, traumatic, or fatal events. The field of urology has been relatively slow to adopt the concept of disease prevention. Several areas of clinical urology do employ prophylactic or metaphylactic therapies, although these are generally for secondary prevention after a primary event (e.g., secondary prevention of recurrent bladder cancer or recurrent kidney stones). There is, however, growing interest in the primary prevention of prostate cancer with a variety of interventions, ranging from dietary modifications to selenium and finasteride. Traditionally, clinical trials of agents for the treatment of symptomatic benign prostatic hyperplasia (BPH) have studied improvements in lower urinary tract symptoms, urinary flow rate, and reduction in prostate volume over relatively short periods of 6 weeks to 1 year. More recently, with the availability of long-term data from community-based studies of the natural history of BPH and placebo-controlled clinical trials, interest is shifting beyond short-term effects on symptoms to reducing the risk of long-term negative outcomes and disease progression. This signals an important reorientation of clinical investigation in BPH.
 ...
PMID:Acute relief or future prevention: is urology ready for preventive health care? 1107 97

Epidemiological and clinical data suggest that selenium may prevent prostate cancer, but the biological effects of selenium on normal or malignant prostate cells are not well known. We evaluated the effects of sodium selenite (Na2SeO3) or l-selenomethionine (SeMet) on monolayer and anchorage-independent growth in a series of normal primary prostate cultures (epithelial, stromal, and smooth muscle) and prostate cancer cell lines (LNCaP, PC-3, and DU145). We observed differential, dose-dependent growth inhibition and apoptosis within prostate cancer cells (compared with normal prostate cells) treated with 1-500 microM of Na2SeO3 or SeMet. Na2SeO3 more potently inhibited growth at any given concentration. The androgen-responsive LNCaP cells were the most sensitive to selenium growth suppression (IC50s at 72 h for Na2SeO3 and SeMet were 0.2 and 1.0 microM, respectively). Growth of the primary prostate cells virtually was not suppressed (IC50s at 72 h for Na2SeO3 and SeMet were 22-38 and >500 microM, respectively). We also observed that DNA condensation and DNA fragmentation (terminal deoxynucleotidyltransferase dUTP nick end labeling/fluorescence-activated cell sorting) were elevated in selenium-treated cells and that activated caspase-3 colocalized with terminal deoxynucleotidyltransferase dUTP nick end labeling-stained cells by immunofluorescence. Higher basal poly(ADP-ribose) polymerase (PARP) expression levels and PARP cleavage (a substrate for caspase-3) were observed during apoptosis in tumor cells, compared with normal cells. Selective tumor cell death was associated with an increase in sub-G0-G1 cells after propidium iodide staining and fluorescence-activated cell sorting analysis. SeMet caused an increase in arrest in the G2-M phase of the cell cycle selectively in cancer cells. Inhibition of cancer cell growth by SeMet was associated with phosphorylation of P-Tyr15-p34/cdc2, which caused growth arrest in the G2-M phase. Anchorage-independent growth of prostate cancer cells in soft agar was sensitive to selenium. Our results suggest that Na2SeO3 is the more potent inducer of apoptosis in normal and cancer prostate cells. Our SeMet results involving PARP and G2-M cell-cycle arrest (cited above) indicate that SeMet selectively induces apoptosis in cancer but not primary cells of the human prostate. Our overall findings are relevant to the molecular mechanisms of selenium actions on prostate carcinogenesis and help demonstrate the selective, dose-dependent effects of selenium (especially SeMet) on prostate cancer cell death and growth inhibition.
 ...
PMID:Selenium effects on prostate cell growth. 1109 24

Male sex, advancing age, racial origin, affected first degree relatives and the ubiquitous 'Western lifestyle' have all been cited as significant risk factors for the development of prostate cancer. Numerous epidemiological studies have been undertaken and others are in place to try and identify specific risk factors but diet has not been conclusively implicated to date. Most of the current prostate research suggests that the roles of dietary fat, soy proteins, selenium and possibly vitamin E are greater in determining the progression or stimulation of established tumours rather than in the development of new tumours per se. Certainly the hypothesis casts some light on the geographic variations of the disease. What part diet and nutritional factors play in the overall jigsaw of prostate cancer development needs to be further established. It is an area that will undoubtedly attract much more research interest in future years.
 ...
PMID:Prostate cancer. What part does diet play? 1114 Feb 14

Prostate cancer lends itself ideally to chemoprevention due to a number of specific features of the disease. These include a high prevalence, long latency time, hormone dependency, the availability of an ideal marker (prostate serum antigen) and, last but not least, the availability of a defined precursor lesion (prostatic intraepithelial neoplasia) among the pathways leading to clinical disease. The large variability in the incidence of the tumor in different geographical regions suggests the possibility of nutritional influences regarding the stimulation and/or inhibition of clinical cancer, as there is a similar prevalence worldwide of the precursor lesion. A great number of publications have dealt with a number of nutritional factors, including fat, phytoestrogens, vitamins (especially vitamin E) and minerals such as selenium and calcium. These are among the most reported substances with a possible influence on disease development; however, unfortunately there are no conclusive results or study outcomes at present which satisfy accepted standards of evidence. Ongoing studies on nutrition and prostate cancer may bring the required evidence to support what is still only an hypothesis at present.
 ...
PMID:Prevention of prostate cancer. 1114 4

Previous work suggested that antiangiogenic activity may be a novel mechanism contributing to the cancer chemopreventive activity of selenium (Se). Because methylselenol has been implicated as an in vivo active chemopreventive Se metabolite, experiments were conducted to test the hypothesis that this metabolite pool might inhibit the expression of matrix metalloproteinase-2 (MMP-2) by vascular endothelial cells and of vascular endothelial growth factor (VEGF) by cancer epithelial cells, two proteins critical for angiogenesis and its regulation. In human umbilical vein endothelial cells (HUVECs), zymographic analyses showed that short-term exposure to methylseleninic acid (MSeA) and methylselenocyanate (MSeCN), both immediate methylselenol precursors, decreased the MMP-2 gelatinolytic activity in a concentration-dependent manner. In contrast, Se forms that enter the hydrogen selenide pool lacked any inhibitory effect. The methyl Se inhibitory effect on MMP-2 was cell dependent because direct incubation with Se compounds in the test tube did not result in its inactivation. Immunoblot and enzyme-linked immunosorbent assay analyses showed that a decrease of the MMP-2 protein level largely accounted for the methyl Se-induced reduction of gelatinolytic activity. The effect of MSeA on MMP-2 expression occurred within 0.5 h of exposure and preceded MSeA-induced reduction of the phosphorylation level of mitogen-activated protein kinases (MAPKs) 1 and 2 (approximately 3 h) and endothelial apoptosis (approximately 25 h). In addition to these biochemical effects in monolayer culture, MSeA and MSeCN exposure decreased HUVEC viability and cell retraction in a three-dimensional context of capillary tubes formed on Matrigel, whereas comparable or higher concentrations of selenite failed to exert such effects. In human prostate cancer (DU145) and breast cancer (MCF-7 and MDA-MB-468) cell lines, exposure to MSeA but not to selenite led to a rapid and sustained decrease of cellular (lysate) and secreted (conditioned medium) VEGF protein levels irrespective of the serum level (serum-free medium vs. 10% fetal bovine serum) in which Se treatments were carried out. The concentration of MSeA required for suppressing VEGF expression was much lower than that needed for apoptosis induction. Taken together, the data support the hypothesis that the monomethyl Se pool is a proximal Se for inhibiting the expression of MMP-2 and VEGF and of angiogenesis. The data also indicate that the methyl Se-specific inhibitory effects on these proteins are rapid and primary actions, preceding or independent of inhibitory effects on mitogenic signaling at the level of MAPK1/2 and on cell growth and survival.
 ...
PMID:Monomethyl selenium--specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. 1117 Feb 62

Randomized controlled trials are regarded as the most definitive of study designs. The randomized controlled trials that have tested nutritional factors for cancer prevention are reviewed. Trials that have tested the effects of nutrients given as high-dose supplements have been largely disappointing, typically showing either no or harmful effects. Possible benefits of vitamin E for prostate cancer prevention and selenium for prostate, colorectal, and lung cancer prevention have emerged only as secondary endpoints in trials conducted for other purposes; confirmatory new trials for these nutrients are now underway or are planned. The limitations of both past and current randomized controlled trials for studying diet-cancer relationships are discussed. The disappointing findings that have emerged from short-term studies of high-dose supplements cannot be interpreted as direct tests of the diet-cancer relationship because high-dose supplements cannot fully simulate the effects of whole foods on cancer risk. As we await findings from current and future trials, we should not forget that the ample evidence from observational epidemiologic research--suggesting that diets rich in fruits and vegetables can reduce the risk of many of the most common cancers--can provide a sound basis for nutritional recommendations aimed at reducing cancer risk.
 ...
PMID:What can randomized controlled trials tell us about nutrition and cancer prevention? 1119 49

Chemoprevention is the use of agents to slow progression of, reverse, or inhibit carcinogenesis thereby lowering the risk of developing invasive or clinically significant disease. With its long latency, high incidence and significant morbidity and mortality, prostate cancer is a relevant target for chemoprevention. Developing rational chemopreventive strategies for prostate cancer requires well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer. Chemopreventive agent requirements are experimental or epidemiologic data showing efficacy, safety on chronic administration, and a mechanistic rationale for activity. Current promising agents include antiandrogens and antiestrogens; steroid aromatase inhibitors; retinoids and their modulators; 5alpha-reductase inhibitors; vitamins D, E, and analogs; selenium compounds; carotenoids; soy isoflavones; dehydroepiandrostenedione and analogs; 2-difluoromethylornithine; lipoxygenase inhibitors; apoptosis inducers; and nonsteroidal anti-inflammatory drugs. Identifying biomarkers and validating them as surrogate endpoints for cancer incidence are critical for prostate chemoprevention trials. Potentially useful biomarkers for prostate chemoprevention are associated with histologic, proliferative, differentiation-related, biochemical, and genetic/regulatory features of prostatic disease. In that the prostate is not easily visualized, critical issues also include adequacy and consistency of tissue sampling. Various drugs for the chemoprevention of prostate cancer are now under evaluation in phase 1, 2, and 3 clinical trials. Cohort selection should be based on various patient characteristics (stage of the disease, previous cancers or premalignant lesions, or high risk factors) and should be conducted within the context of standard treatment.
 ...
PMID:Agents, biomarkers, and cohorts for chemopreventive agent development in prostate cancer. 1129 94

Epidemiologic data suggest that the environment is responsible for most prostate cancers (PCA). One major mechanism by which the environment can influence carcinogenesis is oxidative damage. This refers to the generation of reactive oxygen species (ROS) that then damage important biomolecules, including DNA, protein, and lipids. Experimental observations suggest that oxidative damage is associated with PCA. These include: a) the association of PCA and dietary fat consumption (a major substrate for oxidative stress), b) oxidative biomarker data (suggesting increased oxidative stress among patients with PCA), c) ubiquitous defects in the glutathione-s-transferase pi pathway (a major endogenous antioxidant mechanism), and d) evidence that androgens (an important promoter of PCA growth) work in part via generation of ROS. Perhaps the best indirect evidence for oxidative stress comes from randomized double-blind prevention trials of antioxidants. Vitamin E and selenium have both been shown to reduce prostate cancer incidence. Although PCA prevention was not the primary endpoint of these studies, the statistical likelihood that both would prove beneficial by chance alone is 1 in 400. These data suggest that antioxidants may be beneficial in preventing PCA. Further research including randomized trials is warranted.
 ...
PMID:Antioxidant dietary supplements: Rationale and current status as chemopreventive agents for prostate cancer. 1129 3

Deficiencies of selenium have been associated with an increased cancer risk, and several clinical and animal trials have suggested that improved selenium nutrition may reduce the incidence of several kinds of cancer, including lung, colorectal, and breast. Results from recent trials also show an anticarcinogenic effect of selenium in the prostate. There is converging evidence from epidemiologic, experimental animal, and molecular biology studies for an antitumor effect of selenium. Evidence suggests there are two modes of action of selenium affecting cancer risk: first, by functioning as an essential nutrient that provides the catalytic centers of a number of selenoenzymes, including some with antioxidant and redox functions; second, by serving as a source of selenium metabolytes that affect carcinogenesis in other ways. The first mechanism appears most relevant to protection against cancer initiation, the second against cancer progression. There is conclusive evidence of the increased risk of prostate cancer for a male with a family history of the disease. As a result of this evidence, and the evidence supporting the chemopreventive properties of selenium, this study proposed that a trial to test the effect of selenium on men at high risk for development of prostate cancer is appropriate. This article describes the Australian Prostate Cancer Prevention Trial Using Selenium (APPOSE) trial to test the hypothesis that daily dietary supplementation with selenium will reduce prostate cancer incidence in a population of men who are at increased risk because of a first-degree relative with prostate cancer.
 ...
PMID:A randomized, controlled chemoprevention trial of selenium in familial prostate cancer: Rationale, recruitment, and design issues. 1129 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>