Energetics & Breast Cancer: Obesity, Inflammation, Insulin Resistance & Risl<

UCSD TREC中心的总体目标是聚集跨学科的科学合作者， 解决有关胰岛素抵抗和炎症的问题， 从细胞到社区的乳腺癌致癌作用。在项目1中，我们将使用肥胖小鼠 研究β 3脂肪酸的有益抗炎和胰岛素增敏作用是否 是否会减少乳腺肿瘤的生长和转移以及w3脂肪酸受体GPR 120是否是关键 这些癌症保护作用的中介。在项目2中，我们将在肥胖女性中进行试验， 对膳食常量营养素组成的不同反应（取决于胰岛素抵抗状态）。 结果将包括体重减轻，激素因素，炎症标志物以及营养基因 与IL-6和TNF-α基因多态性相关的相互作用。项目3将调查程度 二甲双胍，一种生活方式干预，或两者兼而有之，可以降低乳腺癌死亡率， 超重/肥胖的绝经后乳腺癌幸存者。我们将使用一种创新的生物标志物桥 将乳腺癌幸存者队列的临床结局与 随机对照试验。项目4将通过使用 分支方程建模技术和人工神经网络来分析加速度计和心脏 项目2和项目3参与者的费率数据。全球定位系统数据，跟踪个人的 时空路径，结合圣地亚哥县现有的地理信息系统数据， 将使我们能够发展致肥胖的环境暴露估计，并将其与代谢风险联系起来， 因素Patterson博士是这个拟建中心的主要研究者，在营养学方面有着丰富的研究经验。 和乳腺癌预防和领导和管理在学术界的强大背景， 行业UCSD TREC中心的中央领导实体将是执行科学委员会， 由项目负责人和核心负责人组成。该委员会将在行政核心的协助下， 共享资源的科学和业务监督（生物统计学和生物信息学， 生物储存库）以及跨学科培训计划和发展和跨TREC 核心试点项目。我们认为，本文提出的TREC中心有可能使重要的 有助于了解肥胖和乳腺癌之间的联系，并提供有关 对预防和控制疾病具有广泛人口影响的干预措施。

The overall objective of ttie UCSD TREC Center is to assemble transdisciplinary scientific collaborators to address questions regarding insulin resistance and inflammation underlying the association of energetics with breast cancer carcinogenesis, from the celi to the community. In Project 1, we will use obese mouse models to investigate whether the beneficial anti-inflammatory and insulin-sensitizing effects of u)3 fatty acids will reduce breast tumor growth and metastasis and whether the w3 fatty acid receptor GPR120 is the critical mediator of those cancer-protective effects. In Project 2, we will conduct a triai in obese women to examine differential response (depending on insuiin resistance status) to dietary macronutrient composition. Outcomes will include weight loss, hormonal factors, and markers of inflammation as well as nutrient-gene interactions associated with polymorphisms in IL-6 and TNF-a genes. Project 3 will investigate the degree to which metformin, a lifestyle intervention, or both, can reduce breast cancer mortality among ovenweight/obese, postmenopausal breast cancer survivors. We will use an innovative Biomarker Bridge design that links clinical outcomes from a breast cancer survivor cohort with intermediate outcomes from a randomized controlled trial. Project 4 will advance the science of energy expenditure estimation by using branched equation modeling techniques and artificial neural networks to analyze accelerometer and heart rate data from participants in Projects 2 and 3. Global Positioning System data, which track individuals' spatial-temporal paths, combined with existing Geographic Information Systems data for San Diego County, will allow us to develop obesogenic environmental exposure estimates and relate these to metabolic risk factors. Dr. Patterson, the PI forthis proposed Center, has considerable research experience in nutrition and breast cancer prevention and a strong background in leadership and management in academia and industry. The central leadership entity ofthe UCSD TREC Center will be the Executive Scientific Committee, composed of Project and Core leaders. This Committee, assisted by the Administrative Core, will provide scientific and operational oversight of the Shared Resources (Biostatistics & Bioinformatics and Biorepository) as well as the transdisciplinary Training Program and the Developmental and cross-TREC Pilot Project Core. We believe that the TREC Center proposed herein has the potential to make significant contributions to understanding the link between obesity and breast cancer and provide insight regarding interventions with broad population impact for prevention and control of disease.