96 research outputs found
Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved
Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The summary relative risk of colon cancer was 1.18 [95%C.I.: 1.06-1.32] for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative pre-cancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicit
IMMUNOPROPHYLAXIE DES CANCERS COLORECTAUX PAR DES GLUCIDES INDIGESTIBLES FERMENTABLES: ETUDES CHEZ LA SOURIS MIN
Thèse de doctorat soutenue le 13 décembre 1999Dietary fiber may prevent colorectal cancer, but this hypothesis is still controversial. One proposed mechanism is the production of butyrate by fermentation. We tested two different butyrogenic fibers (short-chain fructooligosaccharides and type III resistant starch) in opposition to a weak butyrate-producing fiber (wheat bran starch free) in the Min mouse, a genetic model of spontaneous intestinal carcinogenesis. Only the sc-FOS diet protected against colon cancer. It suggests the action of another protecting factor besides butyrate: the chemical nature of the fiber and/or the prebiotic properties of sc-FOS (via lactic bacteria which can act on the immune process). In accordance with this hypothesis, we have observed an amplification of the intestinal immune system. Secondly, two resistant starchs with different chemical properties did not reduce the total number of tumours but reduced the number of small tumours. The addition of lyophilised bifidobacteria to the starch-resistant diet reduced the number of small tumours but increased the number of large tumours showing the concept of the dual immunofacilitation/immunoprotection process. A depletion of T lymphocytes of mice fed with sc-FOS doubled the number of colon tumours in comparison with immunocompetent mice, arguing for the participation of the immune system in the protection. By phenotyping of intra-epithelial lymphocyte, a significant decrease of interleukin 2 receptor was found only in sc-FOS diet. This is a possible indication of a temporary anergy of the local immune system or of the involvement of another activation pathway of the colon IELs. In order to classify the mechanisms, we isolated cell lines conditionally immortalized healthy (Apc +/+) and mutated (Apc Min/+) from of breeding Min mice with immortomouse. This cell culture model using a filter co-culture system allows us to study the influence of indigestible carbohydrates and their fermentation products on lympho-epithelial interactions during carcinogenesis.Certaines fibres alimentaires réduiraient l'apparition des cancers colorectaux mais l'hypothèse reste contreversée. Un des mécanismes fait intervenir la production par fermentation de butyrate. Nous avons testé deux fibres butyrogènes chimiquement différentes (fructo-oligosaccharides à chaîne courte scFOS, et amidon résistant) versus une fibre faiblement productrice de butyrate (son de blé désamidonné) chez la souris Min, un modèle de carcinogenèse intestinale spontanée. Seul le régime scFOS réduisait le nombre de tumeurs coliques et stimulait l'immunité locale. La nature chimique de la fibre ou bien les propriétés prébiotiques des scFOS (ils favorisent la croissance de bactéries lactiques qui agiraient sur la réaction immunitaire) sont donc impliquées. Deux autres types d'amidons résistants réduisaient le nombre de petites tumeurs. L'addition de bifidobactéries à l'un de ces deux régimes réduisait le nombre de petites tumeurs, mais augmentait celui de grosses tumeurs illustrant le concept de modulation par l'immunogénicité de la dualité immunofacilitation/surveillance. La déplétion en lymphocytes T associée au régime scFOS doublait le nombre de tumeurs par rapport aux souris immunocompétentes. Le régime scFOS diminuait l'expression du récepteur à l'IL2 à la surface des lymphocytes intra-épithéliaux (LIE) suggérant la mise en anergie temporaire du système immunitaire, mais pouvant aussi signifier l'implication d'une autre voie d'activation des LIE. Enfin, pour mettre en place une modélisation des intéractions lympho-épithéliales, nous avons croisé des souris C57BL6 et Min avec la souris transgénique Immortomouse et isolé à partir de primo-cultures de muqueuses des lignées cellulaires conditionnellement immortalisées saines et mutées sur Apc. Ce modèle permettra d'étudier en co-culture sur filtre, l'influence des glucides indigestibles et de leurs produits de fermentation sur les interactions lympho-épithéliales au cours de la carcinogenèse
Viandes rouges, charcuteries et cancer du côlon:Rôle central du couple fer héminique/peroxydation lipidique.Vers une prévention par le calcium et les probiotiques des produits laitiers?
Viandes rouges, charcuteries et cancer du côlon:Rôle central du couple fer héminique/peroxydation lipidique.Vers une prévention par le calcium et les probiotiques des produits laitiers?. invitation CNIE
Large intestine intraepithelial lymphocytes from Apc+/+ and Apc+/Min mice and their modulation by indigestible carbohydrates: the IL-15/IL-15Rα complex and CD4+ CD25+ T cells are the main targets.
International audienceWe have shown recently that some indigestible carbohydrate (short-chain fructo-oligosaccharides [sc-FOS]) reduced colon tumor incidence in Apc+/Min mice, and that this effect depended on a functional local immune system. In addition, IL-15 mRNA was concomitantly modulated in the mucosa. Since intraepithelial lymphocytes (IELs) are in close contact with intestinal epithelial cells, these cells are the candidates most likely to be involved in early cancer immunosurveillance. The present study documents the effects of sc-FOS on large intestine IELs (LI-IELs) from Apc+/+ or Apc+/Min mice by analyzing markers related to their phenotype, their activation status, and the cell surface IL-15/IL-5R alpha. In the colons of Apc+/Min mice, fewer LI-IELs expressed surface IL-15/IL-15R alpha. In addition, a lower number of CD4+ LI-IELs expressed CD25, although more LI-IELs expressed CD69, as compared to normal mice. The sc-FOS enriched diet caused a decrease in the proportion of CD25+ LI-IELs and an increase in the percentage of LI-IELs bearing surface IL-15/IL-15R alpha, independently of the Apc gene status. The IL-15/IL-15R alpha increase was, however, higher in Min mice, and returned to a level very similar to that of Apc+/+ mice when the latter mice were fed a low-fiber diet. The sc-FOS-enriched diet specifically induced an increase in CD69+ cells in Apc+/+ mice, and a decrease in the proportion of CD4+ CD25+ LI-IELs in Apc+/Min mice. Some of these modulations could contribute to the development of a better immune anticancer response in the early steps of cancer development
Biochemical and physiological studies of the small heat shock protein Lo18 from the lactic acid bacterium Oenococcus oeni
47 ref.International audienc
Development of a risk-benefit assessment framework: application to beef meat consumption
Development of a risk-benefit assessment framework: application to beef meat consumption. Q-safe International Conferenc
Apc+/Min colonic epithelial cells express TNF receptors and ICAM-1 when they are co-cultured with large intestine intra-epithelial lymphocytes
48 ref.International audienc
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