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营养补充剂预防男性患前列腺癌的作用机制。未来的前列腺癌预防试验取决于对这些途径的识别以促进药物开发。具体目标 1：将比较服用营养补充剂与服用安慰剂的男性前列腺活检的基因表达模式。男性将被随机服用安慰剂、番茄红素或鱼油补充剂，并在研究开始时和三个月后进行前列腺活检。主要结果指标是干预前后基因表达的两倍上升或两倍下降；将比较干预组和安慰剂组之间出现这种结果的男性比例。使用这些标准，我们将确定值得进一步研究的营养反应途径的候选分子靶标。具体目标 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量相关。根据之前的流行病学、体外和体内研究，我们假设总能量、脂肪/肉类/动物产品、乳制品/钙的摄入量较高，而鱼、蔬菜、西红柿/番茄红素、维生素 E 和硒的摄入量较低将与特定的基因表达谱相关。具体目标 3：遵循观察等待方案，营养补充、自我报告的饮食和基因表达模式将与男性前列腺癌的临床进展相关。三个月的干预后，我们将跟踪每个受试者最多九个月（总共 12 个月），以了解其前列腺癌的临床进展（即基于 PSA 动力学、病理学等）。男性每季度都会进行标准临床检查，我们将每隔三个月向每位患者的医生询问患者前列腺肿瘤的状况。我们的实验室在使用可靠的 RNA 扩增方法对前列腺癌男性临床针吸活检进行全基因组分析方面积累了丰富的专业知识。 MENS 研究将在前瞻性随机队列研究的背景下使用基因表达谱。将使用统计方法将流行病学饮食信息与基因表达数据相结合，并将营养干预措施与基因表达数据相关联。结果将通过基因表达水平的独立测定、使用相同临床样本的定量聚合酶链反应来确认。试验后对患者的随访将决定观察等待的结果，并且表现出和未表现出临床进展的患者的基因表达相关性可能会导致前列腺癌靶向治疗的开发。本次试验中收集的 DNA、血清、组织样本和饮食数据将可用于其他计划的未来合作研究。