Mechanisms of Energy Balance and Cancer Prevention

能量平衡与癌症预防的机制

• 批准号: 8135130
• 负责人: Anne M. McTiernan
• 金额: $ 23万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8135130
• 关键词: Animal Model; Basic Science; Behavioral Sciences; Biological; Biological Markers; Biometry; Body Weight decreased; Body mass index; Caloric Restriction; Cardiology; Cell Culture Techniques; Cellular biology; Clinical Trials Design; DNA Repair; Development; Diet; Endocrinology; Epidemiology; Equation; Exercise; Exercise Physiology; Gastroenterology; Genetic Polymorphism; Geographic Locations; Growth; Human; Hyperglycemia; Hyperinsulinism; Immunology; Individual; Inflammation; Insulin Resistance; Laboratories; Leadership; Link; Longevity; Low income; Malignant Neoplasms; Mammary gland; Mathematics; Medicine; Metabolic; Minority; Molecular Biology; Obesity; Pathway interactions; Population; Preventive Intervention; Process; Proteomics; Randomized Controlled Trials; Research Design; Research Personnel; Scientist; Serum; Signal Transduction; T-Cell Receptor-Rearrangement Excision DNA Circles; Teenagers; Testing; Training; Work; Workplace; cancer prevention; carcinogenesis; energy balance; innovation; intervention effect; metabolomics; novel; nutrition; obesity prevention; programs; research study; response; tumorigenesis; young adult

DESCRIPTION (provided by applicant): This is a competitive renewal application (in response to RFA-CA-10-006) "Transdisciplinary Research in Energetics and Cancer (U54)". The overarching theme of the Seattle TREC Center will be to determine mechanisms by which changes in energy balance influences cancer development and progression across the adult lifespan in small-scale and population-level human experimental studies. We propose to elucidate new pathways linking energy balance across the cancer continuum from the general population, to high risk individuals, to cancer survivors, using transdisciplinary methods that we developed in the first 5 years of TREC funding and capitalizing on our strengths in conducting human intervention trials. Project 1 will investigate, in a controlled feeding study, the role of caloric restriction plus a low glycemic load diet vs. low glycemic load diet alone in relation to an integrated set of endpoints: systemic insulin resistance and inflammation, adipose tissue inflammation and gut microbial community. Project 2 will test the effect of our group-based modification of the Diabetes Prevention Program weight loss intervention vs. control on prognosis-related biomarkers in breast cancer survivors including systemic metabolic and inflammatory markers, and breast aspirate cytology, proliferation, and gene expression. Project 3 will conduct a randomized trial evaluating a multi-level obesity prevention intervention in small worksites, where the intervention will include work, home, and neighborhood components. Additional novel work in the 3 projects will examine: weight loss effects on proteomics, caloric restriction effects on adipose expression of aromatase, the intersection of gut health with systemic insulin resistance and inflammation, and biology behavior interactions in weight loss and maintenance. Five Cores will support all Projects: the required Administration, Training/Education & Outreach, and Developmental, the recommended Biostatistics/Bioinformatics, and a Laboratory Core. A team of transdisciplinary researchers will collaborate across projects, including experts in epidemiology, oncology, nutrition, biochemistry, endocrinology, biostatistics, and behavioral science. The education/training and outreach program will include individual trainee mentoring and project experience, journal club, seminars, and national and international symposia and meetings on TREC-related topics. We propose to continue our outstanding record of cross-TREC center collaborations, where we have led several multi-center developmental studies. We propose to continue the strong leadership we have brought to the TREC community, and to continue our international leadership and contributions to the field of energy balance and cancer.

描述（由申请人提供）：这是一份竞争性续期申请（响应RFA-CA-10-006）“能量学和癌症跨学科研究（U 54）”。西雅图TREC中心的首要主题将是在小规模和人群水平的人类实验研究中确定能量平衡变化影响癌症发展和成年期进展的机制。我们建议阐明从普通人群到高风险个体到癌症幸存者的癌症连续体的能量平衡的新途径，使用我们在TREC资助的前5年开发的跨学科方法，并利用我们在进行人类干预试验方面的优势。项目1将在一项对照喂养研究中研究热量限制加低血糖负荷饮食与单独低血糖负荷饮食在一组综合终点方面的作用：全身胰岛素抵抗和炎症、脂肪组织炎症和肠道微生物群落。项目2将测试我们基于组的糖尿病预防计划减肥干预与对照的修改对乳腺癌幸存者中与乳腺癌相关的生物标志物的影响，包括全身代谢和炎症标志物，以及乳房抽吸细胞学，增殖和基因表达。项目3将进行一项随机试验，评估小型工作场所的多层次肥胖预防干预措施，其中干预措施包括工作，家庭和社区组成部分。这三个项目中的其他新工作将研究：减肥对蛋白质组学的影响，热量限制对脂肪芳香化酶表达的影响，肠道健康与全身性胰岛素抵抗和炎症的交叉，以及减肥和维持中的生物学行为相互作用。五个核心将支持所有项目：所需的管理，培训/教育和推广，发展，推荐的生物统计学/生物信息学，以及实验室核心。一个跨学科的研究人员团队将跨项目合作，包括流行病学，肿瘤学，营养学，生物化学，内分泌学，生物统计学和行为科学方面的专家。教育/培训和外联方案将包括个别受训人员指导和项目经验、期刊俱乐部、研讨会以及关于TREC相关主题的国家和国际研讨会和会议。我们建议继续保持我们在跨TREC中心合作方面的出色记录，我们已经领导了几项多中心发展研究。我们提议继续我们为TREC社区带来的强有力的领导，并继续我们在能源平衡和癌症领域的国际领导地位和贡献。

项目成果

Effect of low- and high-glycemic load on circulating incretins in a randomized clinical trial.

一项随机临床试验中低血糖负荷和高血糖负荷对循环肠促胰岛素的影响。

• DOI: 10.1016/j.metabol.2012.07.006
• 发表时间: 2013
• 期刊: Metabolism: clinical and experimental
• 作者: Runchey,ShaunaS;Valsta,LiisaM;Schwarz,Yvonne;Wang,Chiachi;Song,Xiaoling;Lampe,JohannaW;Neuhouser,MarianL
• 通讯作者: Neuhouser,MarianL

Measurement of Circulating Phospholipid Fatty Acids: Association between Relative Weight Percentage and Absolute Concentrations.

• DOI: 10.1080/07315724.2015.1116417
• 发表时间: 2016-09
• 期刊: Journal of the American College of Nutrition
• 影响因子: 3.5
• 作者: Song X;Schenk JM;Diep P;Murphy RA;Harris TB;Eiriksdottir G;Gudnason V;Casper C;Lampe JW;Neuhouser ML
• 通讯作者: Neuhouser ML

Characterization of low molecular weight chemical fractions of dry bean (Phaseolus vulgaris) for bioactivity using Caenorhabditis elegans longevity and metabolite fingerprinting.

使用秀丽隐杆线虫寿命和代谢物指纹图谱来表征干豆（菜豆）的低分子量化学成分的生物活性。

• DOI: 10.1021/jf1007538
• 发表时间: 2010
• 期刊: Journal of agricultural and food chemistry
• 影响因子: 6.1
• 作者: Mensack,MeghanM;Fitzgerald,VanessaK;Lewis,MatthewR;Thompson,HenryJ
• 通讯作者: Thompson,HenryJ