A CLINICAL TRIAL WITH FINASTERIDE AND SELENIUM

正如我们初步的实验室研究所证明的那样， 策略代表了前列腺癌化学预防的一个有希望的范例。虽然我们的互补 项目旨在阐明分子机制，我们建议在本项目中进行临床试验， 直接评价芬达和硒组合的化学预防功效。 拟定研究是一项随机、双盲、安慰剂对照、IIB期干预试验 采用2 × 2析因设计。诊断为早期前列腺癌的患者， 罗斯威尔公园癌症研究所的肿瘤切除术将被招募。受试者将被随机分配至 每日剂量5 mg非那肽或安慰剂和400 ng硒代蛋氨酸的治疗前补充 或安慰剂。补充8-9周后，将在手术期间获得前列腺样本。 主要目的是评估芬氟拉明、硒及其组合对雄激素的影响。 信号这将通过检查前列腺特异性抗原（PSA）的mRNA表达来完成， 激肽释放酶2（KLK 2），两个众所周知的雄激素调节基因。第二个目标是评估细胞凋亡 用硒和芬氟拉明诱导。这将通过使用TUNEL测定、免疫组织化学 活化的caspase-3染色和基于ELISA的细胞凋亡检测方法。此外，我们将 探讨过氧化物氧还蛋白1（Prx 1）通过以下方式干扰雄激素信号抑制的假说： 与PSA的mRNA表达相关。 这项研究将提供关键的人类体内数据的化学预防潜力的芬布地尔 和硒的组合。在试验中收集的组织标本将是一个宝贵的资源， 证实了项目1和2中提出的体外机制研究的结果。

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.