Obesity associated inflammation and postmenopausal breast cancer.

肥胖相关炎症和绝经后乳腺癌。

• 批准号: 8719954
• 负责人: Erin Giles
• 金额: $ 10.9万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-12 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719954
• 关键词: Abdomen; Adipocytes; Adipose tissue; Adverse effects; Affect; Age; Agonist; Ancillary Study; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Award; Biopsy; Blood Circulation; Body fat; Breast; Breast Cancer Cell; Caloric Restriction; Clinical; Clinical Research; Clinical Trials; Coculture Techniques; Collaborations; Complement; Data; Development Plans; Diet; Ensure; Environment; Exercise; Fatty acid glycerol esters; Funding; Gland; Goals; Gonadotropin Hormone Releasing Hormone; Health; Hormonal; Hormones; Human; Ibuprofen; Immunology; In Vitro; Incidence; Inflammation; Inflammatory; Inflammatory Response; Insulin Resistance; Intervention; Knowledge; Leuprolide Acetate; Link; Macrophage Activation; Mammary Neoplasms; Mammary gland; Mediating; Menopause; Mentors; Metabolic; Modeling; Obesity; Operative Surgical Procedures; Outcome; Ovarian; Ovarian Ablation; Ovarian hormone; Ovariectomy; Overweight; Phase; Phenotype; Physical activity; Physiological; Plasma; Play; Postmenopause; Pre-Clinical Model; Predisposition; Production; Rattus; Research; Research Training; Risk; Rodent Model; Role; Sampling; Scientist; Staining method; Stains; System; Techniques; Testing; Therapeutic; Time; Training; Tumor Burden; Tumor Promotion; Weight Gain; Woman; Work; bone; cancer prevention; cancer risk; cancer therapy; career; career development; cytokine; design; energy balance; experience; improved; inflammatory marker; knowledge base; macrophage; malignant breast neoplasm; monocyte; mortality; multidisciplinary; novel; obesity treatment; post-doctoral training; prevent; primary outcome; programs; research study; sedentary; therapy design; tumor; tumor growth; tumor metabolism; tumor microenvironment; tumor progression; tumorigenic

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.

描述（由申请人提供）：该提案概述了一项职业发展计划，旨在帮助Erin Giles博士完成她的博士后培训，并建立了一项针对肥胖症和绝经后乳腺癌的独立研究计划。她的指导培训将在具有乳腺癌，代谢，更年期和免疫学研究专业知识的多学科科学家小组中进行。她的导师博士。 MacLean和Schedin是资金丰富的科学家，他们的合作既专注于肥胖症和绝经后乳腺癌。她的咨询团队Drs中的那些人将补充他们在学员的丰富经验。 Van Pelt，Thor，Anderson和Regensteiner。总的来说，该团队将提供出色的培训环境，使她能够填补工具箱和知识库中的关键空白，从而增强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。在该奖项的培训阶段，她将加强自己的学术活动，建立重要 合作，并获取关键数据和样本，以确保她成功过渡。 独立理由：尽管肥胖与绝经后乳腺癌之间有已知的联系，但这种关联的基础机制尚未完全了解。该提案中将检查的工作假设是，脂肪组织炎症介导了绝经后肥胖对乳腺癌的不利影响，并且这种作用涉及通过肥胖和促进肿瘤促进M2表型将巨噬细胞的一般募集到脂肪组织中。设计：吉尔斯博士将利用骨衍生的巨噬细胞，脂肪组织和人类乳腺癌细胞在共同培养系统中来表征创造肿瘤促进环境的相互作用。她将采用良好的临床前模型来确定抗炎药（布洛芬）和干预措施（热量限制或运动）是否可以抑制随着卵巢功能丧失而发生的炎症反应和肿瘤促进。她将通过医学引起的更年期模型扩展这些研究，以确定运动是否对人类具有相似的影响。这项精心开发的培训和研究计划的累积效应将：1）进一步了解炎症在促进肥胖肿瘤生长中的作用； 2）提交高度竞争性R01的结果； 3）启动PI独立的研究职业，弥合了乳腺癌，代谢和炎症领域。相关性：解开肥胖，更年期，体重增加和炎症之间的相互关系及其对肿瘤进展的综合作用，可以促进设计新型疗法以治疗/预防癌症。将抗炎药的使用与标准肥胖治疗（如热量限制或运动）结合使用，有可能减少与肥胖相关的风险并改善临床结果。