Intermittent food restriction prevents mammary tumors

间歇性食物限制可预防乳腺肿瘤

基本信息

批准号：
7217960
负责人：
Margot P Cleary
金额：
$ 29.16万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7217960
关键词：
Animals Apoptosis Body Weight Body Weight decreased Caloric Restriction Calories Cell Proliferation Chemopreventive Agent Chronic Development Diet Dietary Component Dietary Intervention Effectiveness of Interventions Energy Intake Epidemiologic Studies Etiology Fatty acid glycerol esters Female Gene Expression Goals Growth Factor Health Human Incidence Insulin-Like Growth Factor I Insulin-Like-Growth Factor I Receptor Intervention Leptin Mammary Neoplasms Mammary gland Mediating Modeling Mus Nutrient Obesity Oncogenes Outcome Overweight Postmenopause Protocols documentation Recording of previous events Reporting Risk Rodent Role Serum Signal Pathway Signal Transduction Surrogate Markers Tissues Transgenic Mice Transgenic Organisms Treatment Protocols Tumor Burden Weight Woman cancer risk feeding food restriction insight leptin receptor malignant breast neoplasm prevent protective effect receptor response tumor

项目摘要

DESCRIPTION (provided by applicant): Many attempts have been made to identify dietary components that prevent development of breast cancer and/or mammary tumors (MTs). Few studies have produced conclusive findings. However, chronic caloric restriction consistently lowers MT incidence and extends latency in rodents. We find that intermittent restriction/refeeding prevents MT development in transgenic MMTV-TGF-a mice to a greater degree than does chronic restriction, i.e., 3% vs 44% incidence (vs 77% for ad libitum-fed mice). Thus, the manner in which calories are restricted has a major impact on MT development. Hypotheses: 1- The protective effect of intermittent restriction/refeeding is mediated by decreased serum IGF-I and leptin and effects on signaling pathways and/or proliferation/apoptosis; 2-The protective effect of intermittent restriction/refeeding is dependent upon periods of moderately severe caloric restriction and is modified by caloric intake and/or nutrient composition during refeeding; 3- The protective effects of chronic restriction and intermittent restriction/refeeding are dependent upon tumor etiology. In Specific Aim 1 the effect of intermittent restriction/refeeding and chronic restriction on serum IGF-I and leptin in longitudinal and cross-sectional protocols will be assessed. In Specific Aim 2 the effect of intermittent restriction/refeeding and chronic restriction on apoptosis, proliferation, and gene expression of IGF-I and leptin and their receptors in mammary tissue and MTs will be determined. In Specific Aim 3 the effect of serum leptin levels on the protective response of intermittent restriction/refeeding regimen on MT development will be determined. Specific Aim 4 will determine if the protective effect of intermittent caloric restriction/refeeding is dependent upon the MT oncogene and/or background strain of the transgenic mouse. Our long-term objectives are to establish nutrition intervention strategies applicable to humans and/or to provide insights leading to the development of chemopreventive agents to mimic this protective effect.

描述（由申请人提供）：已经进行了许多尝试来确定预防乳腺癌和/或乳腺肿瘤（MT）发展的饮食成分。很少有研究得出结论性的结论。然而，长期热量限制会持续降低啮齿动物的 MT 发生率并延长潜伏期。我们发现，间歇性限制/再喂养比长期限制更大程度地阻止转基因 MMTV-TGF-a 小鼠的 MT 发育，即，发生率分别为 3% 和 44%（随意喂养的小鼠为 77%）。因此，限制热量的方式对 MT 的发展有重大影响。假设： 1- 间歇性限制/重新喂养的保护作用是由血清 IGF-I 和瘦素减少以及对信号通路和/或增殖/凋亡的影响介导的； 2-间歇性限制/重新喂养的保护作用取决于中度严重热量限制的时期，并根据重新喂养期间的热量摄入和/或营养成分而改变； 3- 长期限制和间歇性限制/再喂养的保护作用取决于肿瘤病因。在具体目标 1 中，将评估纵向和横向方案中间歇性限制/再喂养和长期限制对血清 IGF-I 和瘦素的影响。在具体目标 2 中，将确定间歇性限制/再喂养和长期限制对乳腺组织和 MT 中 IGF-I 和瘦素及其受体的细胞凋亡、增殖和基因表达的影响。在具体目标 3 中，将确定血清瘦素水平对间歇性限制/再喂养方案对 MT 发育的保护反应的影响。具体目标 4 将确定间歇性热量限制/再喂养的保护作用是否取决于转基因小鼠的 MT 癌基因和/或背景品系。我们的长期目标是建立适用于人类的营养干预策略和/或提供有助于开发化学预防剂以模仿这种保护作用的见解。