Time-restricted feeding and breast cancer

限时喂养与乳腺癌

基本信息

  • 批准号:
    10462993
  • 负责人:
  • 金额:
    $ 33.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-04-01 至 2027-08-31
  • 项目状态:
    未结题

项目摘要

There is abundant evidence that obesity confers increased risk for at least 13 forms of cancer. The incidence of breast, colon, and liver cancer are all increased in obese populations, and the epidemiologic evidence for the obesity-breast cancer connection is particularly strong. One in eight women will be diagnosed with breast cancer during their lifetime. Breast cancer incidence increases approximately 10-fold for women over the of age 60, compared to age 50 or younger. This increase in breast cancer risk is associated with an increase in obesity. Indeed, obesity increases the risk of triple-negative breast cancer in premenopausal women and estrogen receptor positive breast cancer in postmenopausal women. A rarer form of inflammatory breast cancer is dramatically increased (up to 5-fold) in both groups. More importantly, obesity shortens disease-free survival in both pre- and postmenopausal women. Patient mortality in breast cancer is primarily caused by distant metastases. Obesity at the time of diagnosis is associated with increased risk of distant metastasis and mortality. Studies in rodents have confirmed these relationships, showing that dietary-induced obesity and high-fat diets lead to increased incidence and growth of tumors in oncogene and carcinogen-induced breast cancers. Despite this body of correlative evidence, the mechanisms of obesity-induced breast cancer risk remain poorly understood. One possibility is that the obesity causes insulin resistance in the liver and compensatory elevation in circulating insulin to control glucose levels. At the same time, other tissues, including tumors, may not be insulin resistant and so are exposed to increased insulin signaling. Indeed, we have shown that reducing insulin resistance by treating with omega-3 fatty acids reduces breast cancer growth in mice. We have also shown that time-restricted feeding (TRF) versus unrestricted feeding of a high-fat diet improves insulin resistance despite sustained obesity and equal caloric intake. Furthermore, we showed that TRF inhibited obesity-driven breast tumor growth and corrected tumor circadian rhythms, and that the TRF impact on tumor growth was mediated by reducing insulin levels. A number of important questions remain unanswered. Firstly, how does insulin drive tumor growth? Is it a direct effect on the tumor cell, or on the microenvironment? Secondly, does correction of the circadian rhythms in the tumor cell by TRF contribute to the reduced tumor growth? Thirdly, how do nutrients and insulin entrain the circadian clock in tumors? Due to the link between obesity, insulin resistance and breast cancer in pre- and postmenopausal women, and the translational potential of time-restricted feeding, we will investigate the effect of deleting the insulin receptor, mTORC1 signaling, or components of the circadian clock in tumor cells to test whether loss of these signals alters tumor growth in vivo and the response to TRF. We will also test whether TRF enhances chemotherapy to inhibit tumor growth. Accumulating evidence from TRF-related clinical studies support the translational relevance of our proposal. Translational, mechanistic findings from these studies will impact on breast cancer prevention and therapy.
大量证据表明,肥胖会增加患至少13种癌症的风险。的

项目成果

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NICHOLAS J WEBSTER其他文献

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{{ truncateString('NICHOLAS J WEBSTER', 18)}}的其他基金

ShEEP Request for MESO SECTOR S 600MM Ultra-Sensitive Plate Imager
ShEEP 请求 MESO SECTOR S 600MM 超灵敏板成像仪
  • 批准号:
    10741205
  • 财政年份:
    2023
  • 资助金额:
    $ 33.96万
  • 项目类别:
SRSF3 degradation in liver disease and hepatocellular carcinoma
肝脏疾病和肝细胞癌中的 SRSF3 降解
  • 批准号:
    10162302
  • 财政年份:
    2020
  • 资助金额:
    $ 33.96万
  • 项目类别:
SRSF3 degradation in liver disease and hepatocellular carcinoma
肝脏疾病和肝细胞癌中的 SRSF3 降解
  • 批准号:
    10618856
  • 财政年份:
    2020
  • 资助金额:
    $ 33.96万
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10454119
  • 财政年份:
    2020
  • 资助金额:
    $ 33.96万
  • 项目类别:
SRSF3 degradation in liver disease and hepatocellular carcinoma
肝脏疾病和肝细胞癌中的 SRSF3 降解
  • 批准号:
    10002586
  • 财政年份:
    2020
  • 资助金额:
    $ 33.96万
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10219156
  • 财政年份:
    2020
  • 资助金额:
    $ 33.96万
  • 项目类别:
SRSF3 degradation in liver disease and hepatocellular carcinoma
肝脏疾病和肝细胞癌中的 SRSF3 降解
  • 批准号:
    10454816
  • 财政年份:
    2020
  • 资助金额:
    $ 33.96万
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10618230
  • 财政年份:
    2020
  • 资助金额:
    $ 33.96万
  • 项目类别:
SRSF3 Loss and Hepatocellular Carcinoma
SRSF3 缺失与肝细胞癌
  • 批准号:
    9205453
  • 财政年份:
    2016
  • 资助金额:
    $ 33.96万
  • 项目类别:
Time-Restricted Feeding and Breast Cancer
限时喂养与乳腺癌
  • 批准号:
    9882965
  • 财政年份:
    2016
  • 资助金额:
    $ 33.96万
  • 项目类别:

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  • 批准号:
    9751077
  • 财政年份:
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Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
  • 批准号:
    9976990
  • 财政年份:
    2011
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  • 批准号:
    10457019
  • 财政年份:
    2011
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预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
  • 批准号:
    10213006
  • 财政年份:
    2011
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