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

加州大学圣迭戈分校TREC中心的总体目标是召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，这是能量学关联的基础 随着乳腺癌的发生，从CELI到社区。在项目1中，我们将使用肥胖的老鼠 研究u)3脂肪酸是否具有抗炎和胰岛素增敏作用的模型 会不会减少乳腺肿瘤的生长和转移以及w3脂肪酸受体GPR120是否是关键 这些防癌作用的中介物。在项目2中，我们将对肥胖女性进行一项试验，以检查 对膳食中大量营养素成分的不同反应(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和肿瘤坏死因子-α基因多态性相关的相互作用。项目3将调查学位 二甲双胍，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，绝经后乳腺癌幸存者。我们将使用创新的Biomarker Bridge 设计将乳腺癌幸存者队列的临床结果与乳腺癌患者的中期结果联系起来 随机对照试验。项目4将推进能源支出估算的科学性，通过使用 分析加速度计和心脏的分支方程建模技术和人工神经网络 来自项目2和项目3参与者的评级数据。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， 将使我们能够开发肥胖环境暴露估计，并将这些估计与代谢风险联系起来 各种因素。帕特森博士是这个拟建中心的PI，他在营养学方面拥有丰富的研究经验 和乳腺癌预防，以及在学术界和 工业。加州大学圣迭戈分校TREC中心的核心领导实体将是执行科学委员会， 由项目领导和核心领导组成。该委员会在行政核心的协助下，将提供 对共享资源的科学和业务监督(生物统计和生物信息学以及 生物资源库)以及跨学科培训方案以及发展和跨TREC 试点项目核心。我们相信，在此提出的TREC中心有可能使 有助于理解肥胖和乳腺癌之间的联系，并提供关于 具有广泛人群影响的预防和控制疾病的干预措施。

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.