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Program Announcement: Diet Induced Changes in Inflammation as Determinants of Colon Cancer.


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Program Announcement: Diet Induced Changes in Inflammation as Determinants of Colon Cancer. Young S. Kim Nutritional Science Research Group Division of Cancer Prevention. Colon Cancer and Inflammation. ● Colon cancer is the 2 nd leading cause of cancer deaths in the United States.
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Program Announcement: Diet Induced Changes in Inflammation as Determinants of Colon Cancer Young S. Kim Nutritional Science Research Group Division of Cancer Prevention

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Colon Cancer and Inflammation ● Colon disease is the 2 nd driving reason for cancer deaths in the United States. ● Chronic incendiary inside illnesses, for example, ulcerative colitis or Crohn's ailment have been appeared to build the danger of colon cancer. ● Use of mitigating operators, for example, headache medicine have appeared to diminish the danger of colon malignancy.

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The Inflammatory Process Inflammatory signs Proinflammatory cytokines Protein kinase C actuation Viruses Anti-provocative cytokines (TGF-β ) Inflammatory proteins Receptors Chemokines Adhesion particles Enzymes Cytokines TNF-an Interleukin-1 b I-ĸ B NF-k B Amplifying circle mRNA p50 p65 Nucleus Inflammatory quality Modified from Barnes, PJ et al. NEJM 336:1066-71, 1997

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Genetics, Inflammation & Colon Cancer Prevention Anti-provocative Mediators (IL-10, TGF β , and so on.) Genetic Polymorphisms and Dietary Factors?? Professional incendiary Mediators (IL-6, TNF α , COX2) Cancer Risk Low High

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Dietary Components Linked to Reduced Colon Cancer Risk Fatty Acids N-6: Conjugated linoleic corrosive N-3: Docosahexaenoic corrosive Eicosapentaenoic corrosive Short chain: Butyrate Minerals Calcium Selenium Vitamins Vitamin A Vitamin D Folate Polyphenols Curcumin Epigallocatechin-3-gallate Genistein Luteolin Quercetin Resveratrol

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Specific Targets for Dietary Components Inflammatory signs Proinflammatory cytokines Protein kinase C enactment Viruses Oxidants Anti-provocative cytokines (TGF-β ) Curcumin EGCG, Luteolin N-3 unsaturated fats Quercetin Inflammatory proteins Receptors Chemokines Adhesion particles Enzymes Cytokines TNF-an Interleukin-1 b I-ĸ B Butyrate Curcumin CLA NF-k B Amplifying circle Resveratrol mRNA p50 p65 Nucleus Inflammatory quality Modified from Barnes, PJ et al. NEJM 336:1066-71, 1997

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Green Tea Suppresses Cytokine Synthesis TNF-α IL-6 100 90 * 80 70 ** % of control 60 50 40 30 20 10 0 - + 0.1% Green tea extricate Sueoka N et al, Ann N Y Acad Sci 928: 274-80, 2001

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TNF-α Polymorphism Influences the Response to Fish Oil in Humans 12 Control 10 Fish Oil 8 TNF-α Production (µg/l) 6 ** 4 2 0 G/A G/G TNF-α Polymorphism at - 308 Grimble et al. Am J Clin Nutr 76:454-9, 2002.

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Bioactive Food Components Preclinical, Epidemiological and Clinical Evidence Suggests Diet, Inflammation, and Colon Cancer May Be Interrelated ?? Irritation Colon Cancer

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Purpose of this PA Use R01 and R21 instruments to cultivate examining research that will figure out whether diet instigated shifts in incendiary procedures represent the counter tumorigenic impacts of bioactive nourishment parts on colon disease.

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Various Models May Be Used in this PA ● Humans ♦ Genetic polymorphisms in incendiary mediators ♦ Inflammatory Bowel Disease (e.g. Crohn's Disease, Ulcerative colitis) ● Animals ♦ Colitis incited irritation in colon ♦ Transgenics (i.e. all the while expressing COX-2 and PGE2 ) ♦ Double knockouts (i.e. APC x Ptgs2 ) ♦ Xenografts

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Required End Point Measurements for this PA Diet affected changes in the provocative procedure must be combined with: ● Aberrant Crypt Foci (ACF): Number, size, the substance of β - Catenin ● Dysplasia or Adenomas of Colon ● Colon malignancy rate

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Some Overarching Topics of Interest ● Are NF κ B and IKK exercises in charge of the efficacy of resveratrol and curcumin in retarding colon disease cell development? ● Can hereditary polymorphisms in TNF-α or IL-6 explain the differential responsiveness to n-3 fatty acids in fish oil concerning colon cancer restraint? ● Can the creation of PGE2 and NO be influenced by dietary conjugated linoleic corrosive and at last adjust colon tumor hazard?

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FY04 NCI Extramural Portfolio Analysis % # $ (M) 2,940 100.0 Total 1,023 347 Cancer Prevention 11.8 198 796 6.7 Nutrition 179 33 1.2 Inflammation 7 0.02 0.5 Combination

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Concept Builds On ● Significance of colon disease rate and mortality in the USA ● Recognized impacts of dietary segments on colon growth ● Role of irritation as an element for colon malignancy ● Recommendations by: - NCI Colorectal Cancer Progress Review Groups (2000) - Nutritional Genomics and Proteomics in Cancer Prevention Workshop (DCP/NIH 2002) - "Tumor Prevention, Early Detection, and Prediction" (NCI Bypass 2006)