Molecular Effects of Nutrition Supplements in Prostate

营养补充剂对前列腺的分子效应

• 批准号: 7085426
• 负责人: PETER R CARROLL
• 金额: $ 32.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-10 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7085426
• 关键词: biopsy; cancer prevention; carotenoids; clinical research; clinical trials; dietary supplements; gene expression; gene expression profiling; human subject; insulinlike growth factor; longitudinal human study; marine animal oil; microarray technology; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplasm /cancer pharmacology; neoplastic process; nucleic acid amplification techniques; nutrition aspect of cancer; nutrition related tag; omega 3 fatty acid; patient oriented research; pharmacokinetics; polymerase chain reaction; prostaglandin endoperoxide synthase; prostate neoplasms; selenium; tocopherols

DESCRIPTION (provided by applicant): Prostate cancer remains the most common and second most fatal cancer among men in the United States. The long term goal of this study is to identify the mechanism of action for nutritional supplements that protect men from developing prostate cancer. Future prostate cancer prevention trials depend on identification of these pathways to facilitate drug development. Specific Aim 1: Gene expression patterns from prostate biopsies among men on nutritional supplements vs. placebo will be compared. Men will be randomized to take placebo, lycopene or fish oil supplements and prostate biopsies will be taken at initiation of the study and at three months. The primary outcome measure is a two-fold up or two-fold down change in gene expression, pre- and post-intervention; the proportion of men with this outcome will be compared between intervention and placebo groups. Using these criteria, we will identify candidate molecular targets for nutrition response pathways deserving further study. Specific Aim 2: Baseline gene expression patterns from initial prostate biopsies will be correlated with self-reported dietary intake. Based on previous epidemiologic, in vitro, and in vivo studies, we hypothesize that higher intakes of total energy, fat/meat/animal products, dairy/calcium, and lower intakes of fish, vegetables, tomatoes/lycopene, vitamin E, and selenium will be associated with particular gene expression profiles. Specific Aim 3: Nutritional supplementation, self-reported diet and gene expression patterns will be correlated with clinical progression of prostate cancer among men following a watchful waiting protocol. After the three-month intervention, we will follow each subject for up to an additional nine months (12 months total) for clinical progression of his prostate cancer (i.e. based on PSA kinetics, pathology, etc). Men will have standard clinical exams quarterly, and we will query each patient's physician regarding the status of the patient's prostate tumor at three-month intervals. Our laboratory has developed considerable expertise in genome-wide analysis of clinical needle biopsies from men with prostate cancer using a faithful RNA amplification method. The MENS study will use gene expression profiling in the context of a prospective randomized cohort study. Statistical methods will be used to combine epidemiologic dietary information with gene expression data, and to correlate nutritional interventions with gene expression data. Results will be confirmed with an independent assay of gene expression levels, quantitative polymerase chain reaction using the same clinical samples. Post trial follow-up of patients will determine the outcome of watchful waiting, and the correlation of gene expression in patients who do and do not exhibit clinical progression may lead to development of targeted therapeutics for prostate cancer. The DNA, serum, tissue samples and dietary data collected in this trial will be available for other planned future collaborative studies.

描述（由申请人提供）： 前列腺癌仍然是美国男性中最常见和第二大致命的癌症。这项研究的长期目标是确定保护男性免受前列腺癌的营养补充剂的作用机制。未来的前列腺预防试验取决于鉴定这些途径以促进药物开发。特定目标1：将比较男性在营养补充剂与安慰剂中的基因表达模式。男性将随机分配安慰剂，番茄红素或鱼油补充剂，前列腺活检将在开始研究时和三个月时进行。主要结局指标是基因表达，干预前和干预后的两倍向上或两倍变化。在干预组和安慰剂组之间将比较具有这种结果的男性的比例。使用这些标准，我们将确定候选分子靶标的营养反应途径，应进行进一步研究。特定目标2：初始前列腺活检的基线基因表达模式将与自我报告的饮食摄入相关。基于先前的流行病学，体外和体内研究，我们假设较高的总能量，脂肪/肉类/动物产品，乳制品/钙以及较低的鱼类，蔬菜，西红柿/番茄，维生素E和硒的摄入量将与特定的基因表达概率相关联。特定目的3：根据注意等待方案，在男性中，营养补充，自我报告的饮食和基因表达模式将与前列腺癌的临床进展相关。三个月的干预后，我们将遵循每位受试者多长达9个月（总共12个月），以进行他的前列腺癌的临床进展（即基于PSA动力学，病理等）。男性每季度将进行标准的临床检查，我们将以三个月的间隔向每个患者的医生查询患者前列腺肿瘤的状态。我们的实验室在使用忠实的RNA扩增方法对患有前列腺癌的男性的临床针头活检的全基因组活检中开发了相当大的专业知识。男士研究将在前瞻性随机队列研究的背景下使用基因表达分析。统计方法将用于将流行病学饮食信息与基因表达数据相结合，并将营养干预与基因表达数据相关联。使用相同的临床样品对基因表达水平，定量聚合酶链反应的独立测定将证实结果。试验后患者的随访将确定注意等待的结果，并且在临床进展和不表现出临床进展的患者中基因表达的相关性可能会导致针对前列腺癌的靶向治疗剂的发展。该试验中收集的DNA，血清，组织样品和饮食数据将用于其他计划的未来协作研究。