Obesity associated inflammation and postmenopausal breast cancer.

描述（由申请人提供）：该提案概述了一个职业发展计划，以帮助Erin Giles博士完成她的博士后培训，并建立一个专注于肥胖和绝经后乳腺癌的独立研究项目。她的指导培训将在一个多学科的科学家小组中进行，这些科学家的研究专长包括乳腺癌、代谢、更年期和免疫学。她的导师，博士。麦克林和舍丁都是资金雄厚的科学家，他们在肥胖和绝经后乳腺癌方面建立了合作关系。她的顾问团队将补充他们与学员的丰富经验。范佩尔，托尔，安德森和雷根斯坦纳。总的来说，这个团队将提供一个优秀的培训环境，使她能够填补她的工具箱和知识库的关键空白，从而提高她研究炎症和肿瘤微环境的能力，并为她提供进行临床研究的能力。在这个奖项的培训阶段，她将加强她的学术活动，建立重要

DESCRIPTION (provided by applicant): This proposal outlines a career development plan to help Dr. Erin Giles complete her postdoctoral training and establish an independent research program focused on obesity and postmenopausal breast cancer. Her mentored training will be conducted in a multidisciplinary group of scientists with research expertise in breast cancer, metabolism, menopause, and immunology. Her mentors, Drs. MacLean and Schedin, are well-funded scientists with established collaborations focused on obesity and postmenopausal breast cancer. Their extensive experience with trainees will be complemented by those in her advisory team, Drs. Van Pelt, Thor, Anderson, and Regensteiner. Collectively, this team will provide an outstanding training environment that will allow her to fill critical gaps in her toolbox and knowledge base that will enhance her ability to study inflammation and the tumor microenvironment, and provide her with the ability to conduct clinical research studies. During the training phase of this award, she will strengthen her scholarly activities, establish important collaborations, and acquire critical data and samples that will ensure her successful transition.to independence Rationale: Despite the known link between obesity and postmenopausal breast cancer, the mechanisms underlying this association are not completely understood. The working hypothesis that will be examined in this proposal is that adipose tissue inflammation mediates the adverse effects of obesity on breast cancer after menopause and that this effect involves the general recruitment of macrophages to adipose tissues by obesity and the promotion of an M2 phenotype by tumors. Design: Dr. Giles will utilize bone derived macrophages, adipose tissues, and human breast cancer cells in co- culture systems to characterize the interactions that create a tumor promoting environment. She will employ a well-established preclinical model to determine whether anti-inflammatory agents (ibuprofen) and interventions (caloric restriction or exercise) can inhibit the inflammatory response and tumor promotion that occurs with the loss of ovarian function. She will extend these studies with a medically-induced model of menopause to determine if exercise has similar effects in humans. The cumulative effect of this carefully developed training and research program will: 1) further our understanding of the role of inflammation in promoting tumor growth in the obese; 2) result in the submission of a highly competitive R01; and 3) launch the PI's independent research career bridging the fields of breast cancer, metabolism, and inflammation. Relevance: Untangling the interrelationship between obesity, menopause, weight gain and inflammation, and their combined effects on tumor progression, could facilitate design of novel therapies for treatment/prevention of cancer. Use of anti-inflammatory agents, in conjunction with standard obesity treatments like as caloric restriction or exercise, has the potential to reduce obesity-associated risk and improve clinical outcomes.