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Dietary Factors in Colon Cancer Prevention

预防结肠癌的饮食因素

基本信息

批准号：
8386941
负责人：
FRANK ALBERT SIMMEN
金额：
$ 27.43万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-15 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8386941
关键词：
Aberrant crypt foci Adult Apoptosis Apoptotic Attenuated Azoxymethane Biological Markers Birth Carcinogens Carcinoma Caseins Cell Proliferation Cell model Colon Colon Carcinoma Colonic Adenoma Colonic Neoplasms DNA DNA Damage Data Development Diet Dietary Factors Dietary Proteins Disease Enzyme Gene Enzymes Epithelial Cell Proliferation Epithelial Cells Epithelium Fatty acid glycerol esters Fatty-acid synthase Food Frequencies Gene Expression Genes Glucose Goals Health Human Hyperinsulinism Incidence Insulin Insulin Receptor Insulin Resistance Insulin-Like Growth Factor I Intestinal Neoplasms Link Lipids Liver Mediating Messenger RNA Metabolic Metabolic syndrome Metabolism Modeling Mucous Membrane Mus Mutant Strains Mice NADP Nutritional Obesity Outcome Overweight Pathway interactions Peptides Perinatal Exposure Pharmaceutical Preparations Physiological Play Populations at Risk Pregnancy Prevention Prevention strategy Preventive Proteins Quality of life Rattus Rectal Cancer Regulation Relative (related person)Risk Rodent Model Role Serum Signal Transduction Soy Proteins Sprague-Dawley Rats Staging Testing Thyroid Gland Thyroid Hormone Receptor Thyroxine Tissues Transgenic Mice Triiodothyronine Receptors cancer initiation cancer prevention cancer risk chemical carcinogen clinically significant design fatty acid biosynthesis feeding fetal programming hormone regulation improved in vivo indexing innovation lipid biosynthesis malic enzyme mortality novel novel strategies obesity prevention programs receptor soy soy protein isolate stem synthetic enzyme tumor tumor initiation tumor progression tumorigenesis young adult

项目摘要

DESCRIPTION (provided by applicant): This project studies novel mechanisms by which dietary factors, using soy protein isolate as the nutritional paradigm, inhibit colon cancers of the rat and mouse (and by inference human). The Central Hypothesis under study posits that dietary soy protein isolate reduces circulating insulin levels and as a consequence, colonic expression of lipogenic enzymes, which in turn confers reduced proliferation and increased apoptosis during colon tumor initiation and progression. Sprague-Dawley rats will be fed high fat diets to induce obesity and hyperinsulinemia. Diets will contain equal amounts of casein (control protein) or soy protein isolate (SPI). These dietary proteins elicited significant differences in intestinal tumor indices after administration of the chemical carcinogen, azoxymethane (AOM). SPI suppressed: a) numbers of aberrant crypt foci (ACF; intermediate end-point biomarker of colon adenomas/carcinomas), b) incidence of colon tumors, c) systemic insulin levels, and d) expression of lipogenic enzyme genes in colon (both prior to and during tumorigenesis). Soy protein, when fed only during pregnancy, influenced the outcome of AOM-induced tumorigenesis in the progeny as later adults ("nutritional programming" of colon cancer). Thus, there is support for linkages of dietary protein type, metabolic regulation of lipid synthetic enzyme genes, and colon cancer. Three Specific Aims will examine these proposed linkages by elucidating the inhibitory actions of dietary SPI on initiation of colon tumorigenesis in the high fat-fed, obese rat; examining the inhibitory actions of dietary SPI on colon tumor progression in the high fat-fed rat and mouse; and investigating mechanisms of obesity-induced fetal programming of colon tumorigenesis. Emphasis in all three Aims will be on lipogenic enzyme genes as downstream pro-proliferative and anti-apoptotic targets of insulin and thyroxine, in obese states. Long-term goals are to utilize proteins/peptides and non-protein bio-active factors present in soy protein isolates, and the targeting of downstream lipogenic enzyme genes/pathways, to augment human colo-rectal cancer- and obesity-prevention strategies. These studies have strong translational significance for improving the health and quality of life of the overweight/obese population at risk for or afflicted with colo-rectal cancer.

描述（由申请人提供）：