Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis, PlanB (M.S.)--University of Wisconsin--Stout, 2005. / Includes bibliographical references.

Thesis (Ph. D.)--University of Sydney, 2009. / Includes tables and questionnaires. Title from title screen (viewed May 14, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Behavioural and Community Health Sciences, Faculty of Health Sciences. Includes bibliography. Also available in print form.

The aim of this study was to investigate the influence of folate on DNA stability and DNA methylation in three different systems. (i) Folate deficiency significantly increased DNA strand breakage and uracil misincorporation in human colon epithelial cells and lymphocytes in vitro. DNA methylation was decreased in both cell types when depleted of folate. (ii) Rats fed a folate-free diet for 10 weeks were moderately folate deficient measured as a 25-50% decrease in plasma, red blood cell or hepatic folate concentrations and a 20% rise in plasma homocysteine, a functional marker for folate status. Folate deficiency specifically increased DNA strand breakage in isolated rat lymphocytes and colonocytes and misincorporated uracil in lymphocytes. (iii) In a human colorectal cancer case-control study, no significant associations were observed between plasma or red blood cell folate, plasma vitamin B12 or homocysteine and lymphocyte DNA strand breakage, misincorporated uracil or DNA methylation. Homozygosity for the C677T polymorphism in the methylenetetrahydrofolate reductase gene was associated with a decreased risk of colorectal cancer, increased plasma homocysteine levels and decreased plasma folate levels compared with heterozygous or wild-type individuals. Plasma vitamin B12 level was associated with a reduction in cancer risk, whereas homocysteine was associated with increased risk of colorectal cancer. DNA strand breakage was associated with increased risk, whereas uracil misincorporation was protective. Red blood cell folate concentrations were not associated with risk. Old age (>65 years) and male gender were associated with increased risk of colorectal cancer.

Les récepteurs activables par les proliférateurs de peroxysomes appartiennent à la superfamille des récepteurs nucléaires aux hormones. Trois isotypes de PPAR ont été identifiés¡: PPAR, PPAR et PPAR. Les PPAR sont impliqués dans la régulation du métabolisme lipidique, dans l homéostasie du glucose, la prolifération cellulaire et dans la réponse inflammatoire. Ils interviennent également dans la carcinogenèse colique et/ou la progression tumorale. Nous avons étudié l effet de l activation de PPAR et par les thiazolidinediones et les fibrates, respectivement, sur l adhérence et la migration de la lignée HT29 dérivant d adénocarcinome colique humain. Nos résultats montrent que les thiazolidinediones et le fénofibrate modifient l expression de gènes impliqués dans l adhérence et la migration des cellules HT29, en particulier lorsqu elles sont exposées de façon chronique. Un traitement long, quel que soit l agoniste, induit l expression de l intégrine 5. La modification de l expression des molécules d adhérence par les thiazolidinediones est, au moins en partie, due à un mécanisme PPAR -dépendant, et l ensemble des effets observés diffèrent selon le temps de traitement, la dose et la nature du ligand. In vivo, les thiazolidinediones inhibent la formation de métastases à distance et diminuent le volume tumoral. Administrée en prévention, la pioglitazone abolit la formation des tumeurs et métastases. Avec la même approche expérimentale, des résultats comparables sont obtenus en utilisant le fénofibrate, ligand de PPAR . En conclusion, un traitement par les agonistes de PPARg et pourrait être intéressant pour l amélioration des traitements actuels du cancer du colon. / Peroxisome proliferator-activated receptors (PPAR) belong to the nuclear hormone receptor family. Three isotypes, encoded by separate genes, have been identified: PPAR, PPAR and PPAR. They are involved in lipid metabolism, glucose homeostasis, cell proliferation and differentiation, and inflammatory response. They have also been implicated in colon carcinogenesis and/or tumour progression. We studied the effect of PPARg and activation by thiazolidinediones and fibrates, respectively, on adhesion and migration of colon adenocarcinoma HT29 cell line. Exposure to thiazolidinedione modifies expression of several genes involved in HT29 cell adhesion and migration, especially when cells are chronically treated with each drug. Of interest, long cell treatment either with pioglitazone, rosiglitazone or fenofibrate induced expression of integrin 5-chain. Our results suggest that the modulation of adhesion molecule expression by thiazolidinediones is partly through PPARg-dependent activation and that effects are different according to the dose and nature of ligand. In vivo, thiazolidinediones especially inhibit distant metastasis formation and diminish tumoral growth. In prevention, pioglitazone abolish tumoral and metastasis development. Using the same experimental approach, we demonstrated that fenofibrate as a ligand of PPAR raised similar results. Collectively, we conclude that treatment with PPARg or agonists may be interesting in the improvement of colon cancer treatment.

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2031-01-01

The ability of ionizing radiation to enhance colon carcinogenesis and the role of diet in this process has not been documented. We hypothesized that radiation would enhance the formation of aberrant crypt foci, ACF, known precursor lesions to colon cancer, by suppressing apoptosis and upregulating proliferation in colonocytes. Diets contained a combination of fish oil or corn oil and either pectin or cellulose. We exposed 40 male Sprague-Dawley rats to 1 Gy ionizing radiation (1 GeV Fe) 10 d prior to injection with AOM. Colons were resected at the promotion stage of carcinogenesis (7 wk post initial injection) and assayed for ACF and apoptosis. Radiation treatment increased (P=0.0327) the incidence of high multiplicity ACF (foci with four or more aberrant crypts) and decreased (P=0.0340) the apoptotic index compared to non-irradiated rats. Radiation also resulted in an increase (P<0.0001) in the proliferative index compared to the nonirradiated rats. The fish oil containing diets resulted in fewer (P=0.0002) high-multiplicity ACF compared to the corn oil treatment. Dietary pectin significantly increased (P=0.0204) the apoptotic index compared to cellulose treatment. These data suggest that ionizing radiation can work synergistically with AOM and increase the formation of high-multiplicity ACF, upregulate cellular proliferation and decrease apoptosis in colonocytes. The data also suggest that diets containing fish oil and pectin may protect against colon cancer by increasing apoptosis and reducing the formation of high multiplicity ACF.

The ability of ionizing radiation to enhance colon carcinogenesis and the role of diet in this process has not been documented. We hypothesized that radiation would enhance the formation of aberrant crypt foci, ACF, known precursor lesions to colon cancer, by suppressing apoptosis and upregulating proliferation in colonocytes. Diets contained a combination of fish oil or corn oil and either pectin or cellulose. We exposed 40 male Sprague-Dawley rats to 1 Gy ionizing radiation (1 GeV Fe) 10 d prior to injection with AOM. Colons were resected at the promotion stage of carcinogenesis (7 wk post initial injection) and assayed for ACF and apoptosis. Radiation treatment increased (P=0.0327) the incidence of high multiplicity ACF (foci with four or more aberrant crypts) and decreased (P=0.0340) the apoptotic index compared to non-irradiated rats. Radiation also resulted in an increase (P<0.0001) in the proliferative index compared to the nonirradiated rats. The fish oil containing diets resulted in fewer (P=0.0002) high-multiplicity ACF compared to the corn oil treatment. Dietary pectin significantly increased (P=0.0204) the apoptotic index compared to cellulose treatment. These data suggest that ionizing radiation can work synergistically with AOM and increase the formation of high-multiplicity ACF, upregulate cellular proliferation and decrease apoptosis in colonocytes. The data also suggest that diets containing fish oil and pectin may protect against colon cancer by increasing apoptosis and reducing the formation of high multiplicity ACF.

Thesis (M. Med. Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 39-45).

Thesis--Coimbra. / Summary in English. Includes bibliography.