The Prostate
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Anti-inflammatory medications have been used for the treatment of chronic prostatitis. The phytotherapeutic agent Eviprostat, a popular treatment for benign prostatic hyperplasia in Japan and Germany, has antioxidant and anti-inflammatory activity. We investigated the effects of the phytotherapeutic agent Eviprostat on prostate inflammation induced in castrated rats by the injection of 17beta-estradiol. ⋯ Eviprostat, which has effective antioxidant and anti-inflammatory activities in the prostate, may be useful for the clinical treatment of chronic prostatitis. These activities of Eviprostat may also contribute to the amelioration of prostate inflammation in BPH patients. Prostate 69: 1404-1410, 2009. (c) 2009 Wiley-Liss, Inc.
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5ARIs are recommended for men who have moderate-to-severe lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) secondary to benign prostatic hyperplasia. Studies have confirmed the utility of combining 5ARIs with alpha-blockers; the MTOPS study showed that risk of overall clinical progression was significantly reduced after 4.5 years with combination therapy (finasteride/doxazosin) in comparison with either monotherapy, while the ongoing CombAT trial (dutasteride/tamsulosin) has for the first time shown benefit in improving symptoms for combination therapy over monotherapies within 12 months of treatment. Data also suggest roles for 5ARIs in prostate cancer. ⋯ The ongoing REDUCE study will provide further insight into prostate cancer prevention with 5ARIs. 5ARI-containing regimens may have utility as less aggressive treatment options for patients who only have rising PSA after definitive local therapy, and in patients with disease resistant to androgen deprivation therapy who have PSA progression. Current evidence therefore shows that 5ARIs are effective in treating LUTS/BPE and preventing disease progression, and may also have a role in the prevention of prostate cancer. The overlap between BPE and prostate cancer may allow a more unified approach to managing these conditions, with 5ARIs having a central role.
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The noninvasive, early detection of Prostate Intraepithelial Neoplasia (PIN), a precancerous neoplasia of the prostate, would be highly desirable. In our experiments, we used TRAMP mice to model PIN in the range of grade 1 through grade 4. ⋯ This method has the potential for early noninvasive detection of developing prostate cancer.
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Prostate tumors initially regress in response to androgen-ablation therapy. However, most cancers eventually relapse with an androgen-depletion-independent (ADI) phenotype that is often more aggressive than the original androgen-dependent (AD) tumor. Importantly, most relapsed tumors still rely upon androgen receptor (AR) activity for proliferation and survival. The cellular Fas/FasL-associated death domain protein-like inhibitory protein (FLIP) inhibits activation of procaspase-8 by death receptor-mediated signaling at the cell surface. In the current study, we examined the androgenic regulation of FLIP and its contribution to protecting prostate cancer cells from death receptor-mediated apoptosis. ⋯ Androgenic protection from TRAIL-induced apoptosis is predominantly via enhanced transcription of FLIP in prostate cancer cells. Loss of androgen-sensitivity in ADI prostate cancer cells highlights this pathway as a potential target for future therapy of prostate cancer.
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The standard hormonal therapy with currently available antiandrogens and the leutinizing hormone releasing hormone (LHRH) analogs is not effective in the hormone-refractory stage of prostate cancer due to changes in androgen receptor (AR) signaling axis. In this refractory stage, AR continues to play a significant role in the growth of cancer cells even though the cancer cells are no longer dependent on the level of circulating androgens. ⋯ The results of this study validate our drug discovery rationale based on the structural biology of AR and pave the pay for future development of bifunctional compounds in order to block AR function in hormone refractory stage of prostate cancer.