Diet, Endocrine-Immune Interactions & Prostate Cancer

饮食、内分泌免疫相互作用

• 批准号: 6783152
• 负责人: TAMMY M BRAY
• 金额: $ 26.6万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6783152
• 关键词: cancer prevention; cell proliferation; estrogen receptors; free radical oxygen; gel mobility shift assay; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory rat; neoplasm /cancer epidemiology; neoplasm /cancer nutrition therapy; nuclear factor kappa beta; nutrition aspect of cancer; nutrition related tag; oxidative stress; prostate neoplasms; sex hormones

DESCRIPTION (provided by applicant) Prostate cancer is the most frequently diagnosed non-cutaneous cancer, and is the second leading cause of cancer death in American men. It has been observed that elevated blood estrogen in the presence of high testosterone is an important risk factor that contributes to the prostate carcinogenesis. Dietary factors potentially linked to prostate cancer are numerous; however, an understanding of the mechanism(s) by which certain nutrients would protect the prostate from the genetic damage that is associated with tumor development remains unclear. The objectives of this application are to define the molecular mechanisms that link sex hormonal (estrogens/testosterone) stimulation to chronic inflammation, generation of reactive oxygen species (ROS) and uncontrolled prostate cell proliferation, and to evaluate the effectiveness of dietary strategies that target these processes. The central hypothesis of this application is that elevated estrogen, in the presence of high testosterone, causes prolonged activation of a redox-sensitive transcription factor, NFkappaB, through an estrogen receptor-mediated process. Prolonged NFkappaB activation initiates and amplifies an inflammatory cascade within the prostate and results in sustained oxidative damage and signals for cell proliferation in the prostate. We further hypothesize that consumption of antioxidant-rich foods containing a combination of anti-estrogenic, anti-inflammatory and anti-proliferative components will be effective in reducing the prevalence of prostate cancer. The Aims of this project are: 1) to identify the molecular mechanisms by which exposure to elevated estrogen/testosterone causes chronic inflammation in prostate tissues of Noble rats, 2) to characterize the links of chronic inflammation leading to oxidative stress and proliferation signals in the prostate during sex hormone-induced prostate carcinogenesis, and 3) to evaluate the ability of novel whole food-based dietary modifications to prevent sex hormone-induced prostate carcinogenesis in Noble rats. The successful completion of our study is expected to reveal novel relationships among divergent factors involved in prostate cancer and aid in identifying key molecular targets for dietary intervention for prostate cancer prevention. Our 'whole food' based approach to cancer prevention is highly relevant to the development of evidence based and broadly applicable public health recommendations that will significantly reduce the burden of prostate cancer.

描述（由申请人提供） 前列腺癌是最常见的非皮肤癌，也是美国男性癌症死亡的第二大原因。已经观察到，在高睾酮存在下升高的血液雌激素是促成前列腺癌发生的重要危险因素。与前列腺癌潜在相关的饮食因素有很多;然而，对某些营养素保护前列腺免受与肿瘤发展相关的遗传损伤的机制的理解仍然不清楚。本申请的目的是定义将性激素（雌激素/睾酮）刺激与慢性炎症、活性氧（ROS）生成和不受控制的前列腺细胞增殖联系起来的分子机制，并评估针对这些过程的饮食策略的有效性。本申请的中心假设是，在高睾酮存在下，升高的雌激素通过雌激素受体介导的过程引起氧化还原敏感性转录因子NF κ B的延长激活。延长的NF κ B激活启动并放大前列腺内的炎症级联反应，并导致前列腺中持续的氧化损伤和细胞增殖信号。我们进一步假设，食用富含抗氧化剂的食物，含有抗雌激素，抗炎和抗增殖成分的组合，将有效降低前列腺癌的患病率。该项目的目标是：1）鉴定暴露于升高的雌激素/睾酮引起Noble大鼠前列腺组织中慢性炎症的分子机制，2）表征在性行为诱导的前列腺癌发生过程中导致前列腺中氧化应激和增殖信号的慢性炎症的联系，和3）评价新的基于全食物的饮食改变预防Noble大鼠中性行为诱导的前列腺癌发生的能力。我们研究的成功完成有望揭示前列腺癌相关的不同因素之间的新关系，并有助于确定预防前列腺癌饮食干预的关键分子靶点。我们基于“全食物”的癌症预防方法与制定基于证据和广泛适用的公共卫生建议高度相关，这些建议将显着降低前列腺癌的负担。