A CLINICAL TRIAL WITH FINASTERIDE AND SELENIUM

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As our preliminary laboratory studies have demonstrated, the finasteride and selenium combination strategy represents a promising paradigm for prostate cancer chemoprevention. While our complementary projects aim to elucidate molecular mechanisms, we propose in this project to conduct a clinical trial to directly evaluate the chemopreventive efficacy of the finasteride and selenium combination. The proposed study is a randomized, double-blind, placebo-controlled, phase IIB intervention trial that employs a 2X2 factorial design. Patients diagnosed with early stage prostate cancer who have opted for prostatectomy at Roswell Park Cancer Institute will be recruited. The participants will be randomized to pretreatment supplementation by daily doses of 5 mg finasteride or placebo, and 400 ng selenomethionine or 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 androgen signaling. This will be done by examining the mRNA expression of prostate specific antigen (PSA) and kallikrein 2 (KLK2), two well-known androgen-regulated genes. A secondary goal is to evaluate apoptosis induction by finasteride and selenium. This will be done by using the TUNEL assay, immunohistochemical staining of activated caspase-3, and an ELISA-based apoptosis detection method. In addition, we will explore the hypothesis that peroxiredoxin 1 (Prx 1) interferes with the suppression of androgen signaling by finasteride/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 finasteride and selenium combination. The tissue specimens collected in the trial will be a valuable resource for corroborating the findings from the in vitro mechanistic studies proposed in projects 1 and 2.