A CLINICAL TRIAL WITH FINASTERIDE AND SELENIUM

非那雄胺和硒的临床试验

• 批准号: 7254399
• 负责人: James Marshall
• 金额: $ 32.56万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7254399
• 关键词: Androgen Suppression; Androgens; Apoptosis; Chemoprevention; Chemopreventive Agent; Clinical Trials; Daily; Data; Depressed mood; Detection; Diagnosis; Dose; Double-Blind Method; Finasteride; Genes; Goals; Human; Human Glandular Kallikrein 2; In Vitro; Induction of Apoptosis; Intervention Trial; Laboratory Study; Localized; Malignant neoplasm of prostate; Methods; Molecular; Operative Surgical Procedures; Participant; Patients; Phase; Placebo Control; Placebos; Prostate; Prostate-Specific Antigen; Prostatectomy; Randomized; Recruitment Activity; Resources; Roswell Park Cancer Institute; Sampling; Selenium; Selenomethionine; Signal Transduction; Specimen; Staging; Staining method; Stains; Supplementation; TdT-Mediated dUTP Nick End Labeling Assay; Tissues; Week; base; caspase-3; design; in vivo; mRNA Expression; peroxiredoxin I

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.

正如我们的初步实验室研究表明，非那雄胺和硒的组合 该策略代表了前列腺癌化学预防的一个很有前途的范例。虽然我们的互补性 为了阐明分子机制，我们在这个项目中建议进行一项临床试验，以 直接评价非那雄胺和硒联合应用的化学预防效果。 建议的研究是一项随机、双盲、安慰剂对照的IIB期干预试验 这采用了2X2析因设计。被诊断为早期前列腺癌的患者选择 罗斯威尔公园癌症研究所的前列腺摘除手术将被招募。参赛者将被随机分配到 预先补充每日5毫克非那雄胺或安慰剂和400毫克硒蛋氨酸 或者安慰剂。在补充8-9周后，将在手术中获取前列腺样本。 主要目的是评估非那雄胺、硒及其组合对雄激素的影响。 发信号。这将通过检测前列腺特异性抗原(PSA)和 激肽释放酶2(KLK2)是两个已知的雄激素调节基因。第二个目标是评估细胞凋亡。 非那雄胺和硒诱导。这将通过使用TUNEL分析，免疫组织化学来完成 活化的caspase-3的染色，以及基于ELISA法的细胞凋亡检测方法。此外，我们还将 探讨过氧化还蛋白1(PRX 1)通过以下途径干扰雄激素信号传导的假说 非那雄胺/硒，PRX-1和PSA的mRNA表达呈正相关。 这项研究将提供有关非那雄胺化学预防潜力的关键人体数据。 和硒的结合。在试验中收集的组织标本将是 证实了项目1和2中提出的体外机制研究的结果。