As our preliminary laboratory studies have demonstrated, the finasteride and selenium combinationstrategy represents a promising paradigm for prostate cancer chemoprevention. While our complementaryprojects aim to elucidate molecular mechanisms, we propose in this project to conduct a clinical trial todirectly evaluate the chemopreventive efficacy of the finasteride and selenium combination. The proposed study is a randomized, double-blind, placebo-controlled, phase IIB intervention trialthat employs a 2X2 factorial design. Patients diagnosed with early stage prostate cancer who have opted forprostatectomy at Roswell Park Cancer Institute will be recruited. The participants will be randomized topretreatment supplementation by daily doses of 5 mg finasteride or placebo, and 400 ng selenomethionineor placebo. After 8-9 weeks of supplementation, prostate samples will be obtained during surgery. The primary goal is to assess the impact of finasteride, selenium, and their combination on androgensignaling. This will be done by examining the mRNA expression of prostate specific antigen (PSA) andkallikrein 2 (KLK2), two well-known androgen-regulated genes. A secondary goal is to evaluate apoptosisinduction by finasteride and selenium. This will be done by using the TUNEL assay, immunohistochemicalstaining of activated caspase-3, and an ELISA-based apoptosis detection method. In addition, we willexplore the hypothesis that peroxiredoxin 1 (Prx 1) interferes with the suppression of androgen signaling byfinasteride/selenium, correlating the mRNA expression of Prx 1 with that of PSA. This study will provide key human in vivo data on the chemopreventive potential of the finasterideand selenium combination. The tissue specimens collected in the trial will be a valuable resource forcorroborating the findings from the in vitro mechanistic studies proposed in projects 1 and 2.
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