title: Search for novel circulating cancer chemopreventive biomarkers of dietary rice bran intervention in Apc(Min) mice model of colorectal carcinogenesis, using proteomic and metabolic profiling strategies.
abstract: METHODS
  There is strong epidemiological evidence indicating that consumption by humans of whole-grain foods including rice bran may be associated with a low incidence of cancer, especially in the colorectum. Molecular processes associated with cancer development may be retarded by fiber consumption. Consequently, intervention with dietary fiber might be suitable as a cancer chemoprevention strategy in high-risk populations. Here, we searched for putative molecular mechanism-based efficacy biomarkers of rice fiber consumption in the plasma of mice characterized by a genetic propensity to develop gastrointestinal adenomas. The hypothesis was tested that metabolic and proteomic changes in blood reflect the chemopreventive activity of rice bran.
  
  
  RESULTS
  Apc(Min) mice received diet supplemented with rice bran at 5, 15, and 30%. Blood and tissue samples were taken. Plasma was subjected to MS-based proteomic and metabolic profiling analyses as well as assessment of hematocrit values. Gastrointestinal tracts were removed and adenomas were counted and their size was measured so that total tumor burden could be calculated. The hypothesis was tested that metabolic and proteomic changes in blood reflect chemopreventive activity.
  
  
  CONCLUSIONS
  Rice bran consumption reduced adenoma burden and number in a dose-related fashion when compared to controls. Metabolic profiling data demonstrated strong clustering of the groups indicating that metabolic pathways are perturbed. Proteomic analysis identified adiponectin as a molecule that was significantly altered, which may play a role in tumor suppression.
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, UK.
authors.forename: Leonie
authors.initials: L
authors.lastname: Norris
authors.affiliation: Centre for Analytical Science, Department of Chemistry, Loughborough University, Loughborough, Leicestershire, UK.
authors.forename: Aditya
authors.initials: A
authors.lastname: Malkar
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Horner-Glister
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, UK.
authors.forename: Amirmansoor
authors.initials: A
authors.lastname: Hakimi
authors.affiliation: Department of Cardiovascular Sciences, NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Leong L
authors.initials: LL
authors.lastname: Ng
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, UK.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Gescher
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Creaser
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, UK.
authors.forename: Stewart
authors.initials: S
authors.lastname: Sale
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, UK.|Department of Cardiovascular Sciences, NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Donald J L
authors.initials: DJ
authors.lastname: Jones
mesh_terms: D000236:Adenoma / Q000178:diet therapy / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000178:diet therapy* / Q000473:pathology; D004032:Diet / Q000662:veterinary; D004043:Dietary Fiber / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D055432:Metabolomics; D051379:Mice; D012275:Oryza / Q000737:chemistry; D040901:Proteomics; D000067348:Whole Grains / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D004043:Dietary Fiber
keywords: Chemoprevention; Colorectal Cancer; Fiber; Metabolite profiling; Mouse models of carcinogenesis; Proteomics