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Abstract: 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] exerts anti-proliferative, differentiating and apoptotic effects on prostatic cells. These activities, in addition to epidemiologic findings that link Vitamin D to prostate cancer risk, support the use of 1,25(OH)2D3 for prevention or therapy of prostate cancer. The molecular mechanisms by which 1,25(OH)2D3 exerts antitumor effects on prostatic cells are not well-defined. In addition, there is heterogeneity among the responses of various prostate cell lines and primary cultures to 1,25(OH)2D3 with regard to growth inhibition, differentiation and apoptosis. To understand the basis of these differential responses and to develop a better model of Vitamin D action in the prostate, we performed cDNA microarray analyses of primary cultures of normal and malignant human prostatic epithelial cells, treated with 50nM of 1,25(OH)2D3 for 6 and 24h. CYP24 (25-hydroxyvitamin D3-24-hydroxylase) was the most highly upregulated gene. Significant and early upregulation of dual specificity phosphatase 10 (DUSP10), validated in five additional primary cultures, points to inhibition of members of the mitogen-activated protein kinase (MAPK) superfamily as a key event mediating activity of 1,25(OH)2D3 in prostatic epithelial cells. The functions of other regulated genes suggest protection by 1,25(OH)2D3 from oxidative stress. Overall, these results provide new insights into the molecular basis of antitumor activities of Vitamin D in prostate cells. [Copyright &y& Elsevier]

The article focuses on a study which examined the effect of reduced physician reimbursement for luteinizing hormone-release hormone (LHRH) agonists on the clinical utilization of LHRH agonists in the U.S. The study explored the sensitivity of physicians to changes in LHRH agonist reimbursement through an analysis of the claims and reimbursement data from the Centers for Medicare and Medicaid Services from 2003 to 2007. Study authors concluded that the decreased use of LHRH agonist in the country is multifactorial.

Background: 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] exerts growth inhibitory, pro-differentiating, and pro-apoptotic effects on prostate cells. To better understand the molecular mechanisms underlying these actions, we employed cDNA microarrays to study 1,25(OH)2D3-regulated gene expression in the LNCaP human prostate cancer cells., Methods: mRNA isolated from LNCaP cells treated with vehicle or 50 nM 1,25(OH)2D3 for various lengths of time were hybridized to microarrays carrying approximately 23,000 genes. Some of the putative target genes revealed by the microarray analysis were verified by real-time PCR assays., Results: 1,25(OH)2D3 most substantially increased the expression of the insulin-like growth factor binding protein-3 (IGFBP-3) gene. Our analysis also revealed several novel 1,25(OH)2D3-responsive genes. Interestingly, some of the key genes regulated by 1,25(OH)2D3 are also androgen-responsive genes. 1,25(OH)2D3 also down-regulated genes that mediate androgen catabolism., Conclusions: The putative 1,25(OH)2D3 target genes appear to be involved in a variety of cellular functions including growth regulation, differentiation, membrane transport, cell-cell and cell-matrix interactions, DNA repair, and inhibition of metastasis. The up-regulation of IGFBP-3 gene has been shown to be crucial in 1,25(OH)2D3-mediated inhibition of LNCaP cell growth. 1,25(OH)2D3 regulation of androgen-responsive genes as well as genes involved in androgen catabolism suggests that there are interactions between 1,25(OH)2D3 and androgen signaling pathways in LNCaP cells. Further studies on the role of these genes and others in mediating the anti-cancer effects of 1,25(OH)2D3 may lead to better approaches to the prevention and treatment of prostate cancer., (Copyright 2004 Wiley-Liss, Inc.)