Energetics & Breast Cancer: Obesity, Inflammation, Insulin Resistance & Risk

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，从细胞到社区，解决有关胰岛素抵抗和炎症的问题，这些问题是能量与乳腺癌发生关联的基础。在项目1中，我们将使用肥胖小鼠模型来研究omega 3脂肪酸的有益抗炎和胰岛素增敏作用是否会减少乳腺癌的生长和转移，以及w3脂肪酸受体GPR120是否是这些癌症保护作用的关键介质。在项目2中，我们将在肥胖女性中进行一项试验，以检查对饮食中大量营养素成分的不同反应(取决于胰岛素抵抗状况)。结果将包括体重减轻、激素因素和炎症标志物，以及与IL-6和肿瘤坏死因子-α基因多态相关的营养-基因相互作用。项目3将调查二甲双胍、生活方式干预或两者兼而有之在多大程度上可以降低超重/肥胖、绝经后乳腺癌幸存者的乳腺癌死亡率。我们将使用一种创新的Biomarker Bridge设计，将乳腺癌幸存者队列的临床结果与随机对照试验的中间结果联系起来。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项目2和项目3参与者的加速计和心率数据，从而推动能源消耗估计的科学。全球定位系统数据跟踪个人的时空路径，与圣地亚哥县现有的地理信息系统数据相结合，将使我们能够开发出致病环境暴露估计，并将这些估计与代谢风险因素联系起来。帕特森博士是这个拟建中心的私募，在营养和乳腺癌预防方面拥有丰富的研究经验，并在学术界和工业界的领导和管理方面拥有强大的背景。加州大学圣迭戈分校TREC中心的核心领导实体将是由项目和核心领导组成的执行科学委员会。该委员会将在行政核心的协助下，对共享资源(生物统计、生物信息学和生物资源库)以及跨学科培训计划、开发和跨TREC试点项目核心进行科学和业务监督。我们相信，这里提出的TREC中心有可能为了解肥胖和乳腺癌之间的联系做出重大贡献，并为预防和控制疾病提供具有广泛人群影响的干预措施的洞察力。

The overall objective of the 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 cell to the community. In Project 1, we will use obese mouse models to investigate whether the beneficial anti-inflammatory and insulin-sensitizing effects of omega 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 trial in obese women to examine differential response (depending on insulin 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 overweight/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 for this 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 of the 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.