Browsing by Subject "colon cancer"

Now showing 1 - 4 of 4
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    Colonoscopic Screening Shows Increased Early Incidence and Progression of Adenomas in Cystic Fibrosis
    (2017-01) Niccum, David
    Background. Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance. Methods. We analyzed prospectively collected results of colonoscopies initiated at age 40 years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30-39 years performed during the same time period at the Center. Results. The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression. Conclusions. Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population.
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    The Effects of Diverse Dietary Interventions on Markers of Colon Cancer Risk in Carcinogen-Treated Rodents
    (2023-12) Bailey, Allison
    Colon cancer, a leading cause of cancer-related deaths worldwide, is largely preventable through lifestyle modifications including diet. While epidemiologic evidence associates foods rich in phytochemicals and dietary fiber with a reduced risk of cancer, the chemopreventive efficacy of specific dietary interventions to reduce colon cancer risk is still uncertain. In four studies, this thesis aims to explore the effects of three dietary interventions (red wheat, apiaceous and cruciferous vegetables, and prebiotic dietary fiber) on colon cancer risk in rodents and to characterize the effectiveness of the Total Western diet as a rodent background diet for colon cancer and inflammatory disease models. The first study used a mouse model to explore the effects of different wheat classes and milling fractions on colon cancer prevention. However, the results were inconclusive. Ultimately this mouse model was unsuitable due to challenges with the carcinogen dosage and toxicity, tissue incompatibility with a major biomarker assay, and the limited volume of tissue available for study due to a mouse’s small size. The second study continued this work using a rat model and added the variable of a comparison of background diets: a standard, optimized rodent diet (AIN-93G) or a newer diet based on the typical Western diet (Total Western Diet; TWD). We found some evidence that whole red wheat may reduce CC risk, but only with the TWD background diet, indicating that TWD may be a better background diet for CC rodent models. The third study examined the effects of apiaceous and cruciferous vegetables on colonic inflammation and compared TWD with the Diet Induced Obesity (DIO) model, which uses the same micronutrient concentrations as the AIN-93G diet. Vegetables decreased colon inflammation, but only with the TWD background diet, further supporting its use in modeling lifestyle diseases. The final study examined the effects of prebiotic dietary fibers, including the novel prebiotic fiber polylactose, on CC risk. We found no evidence that polylactose decreases CC risk, but limited evidence that polydextrose decreases CC risk indicates the need for further research in this area. Taken together, these studies expand our understanding of the effect of diet on CC risk by highlighting the detrimental role of mild micronutrient deficiency modeled by the TWD and providing modest support for consuming nutrient rich foods such as whole red wheat, apiaceous and cruciferous vegetables, and prebiotic fibers to reduce CC risk.
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    The Effects of Green Tea Catechins on Oxidative Stress and Red Wheat on Measures of Oxidative and Nitrosative Stress, Colon Cancer Risk, and Gut Microbiome Composition
    (2021-09) Fiecke, Chelsey
    There have been very few long-term investigations of the in vivo antioxidant effects associated with consumption of green tea catechins, especially in healthy populations. In the first study, we evaluated the in vivo antioxidant effects of 12-month green tea catechin supplementation in healthy, postmenopausal women by measuring urinary excretion of secondary lipid peroxidation products. Green tea catechin supplementation reduced excretion of a nonpolar aldehyde that was identified as nonanal and/or decatrienal. Our results suggest that green tea catechins may exert modest antioxidant effects in healthy populations that do not have elevated oxidative stress.We previously reported that red wheat, the class of wheat used to make yeast bread products, reduced various colon cancer biomarkers. In the second study, we evaluated the chemopreventive effects of red wheat and the aleurone and testa layers by examining morphological markers of colon cancer risk (aberrant crypt foci; ACF), a cancer stem cell marker (doublecortin-like kinase 1; Dclk1), a marker of oxidative and nitrosative stress (3-nitrotyrosine; 3-NT), and gut microbiome composition. The number of medium ACF (3-5 aberrant crypts/ACF) was reduced by consumption of refined red wheat and the aleurone layer. Large ACF (≥ 6 aberrant crypts/ACF) were decreased by the whole and refined red wheat and refined white wheat. Refined red wheat and the aleurone and testa layers reduced 3-NT positivity in aberrant crypts. The microbiome composition differed between diet groups and was driven by altered abundances of Faecalitalea, Lactobacillus, Mucispirillum, and Phascolarctobacterium. Consumption of whole and refined red wheat resulted in enrichment of Faecalitalea and Lactobacillus and depletion of Mucispirillum. These results suggest that the aleurone and testa layers may be partially responsible for the chemoprevention by red wheat, which possibly involves reductions in oxidative/nitrosative stress and modulation of the gut microbiome. In summary, green tea catechins may exert modest antioxidant effects, even under physiological conditions of little oxidative stress. The aleurone and testa layers may play a role in chemoprevention by red wheat, which involves a reduction in oxidative/nitrosative stress and beneficial modulation of gut microbiome composition.
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    Untangling the dynamics of host-microbiome interactions
    (2022-07) Muehlbauer, Amanda
    The gut microbiome performs numerous important functions for the host and has been closely linked to the development of certain diseases. Extreme variation in gut microbiome composition has been observed between different primate species, between individuals within the same species, and in individuals in various disease states. It is unclear how the gut microbiome can impact host physiology, and the effect that the gut microbiome has on host gene expression remains poorly understood. One hypothesis is that the gut microbiome regulates gene expression in host cells, which can affect host physiology and contribute to the development of various chronic diseases and cancers. However, due to the complexity of the gut microbiome and the various confounding factors that shape its composition, establishing causal relationships between variation in the microbiome and the host is inherently difficult to do in vivo. Here, we have used a novel in vitro co-culture system to characterize the impact of variation in the gut microbiome on host gene regulation. First, we tested how variation in gut microbiome composition between five healthy human individuals drives changes in gene expression in colonic epithelial cells. We found that specific microbes in the microbiome may be regulating host gene expression in the gut, and that these genes are related to complex traits. Next, we expanded this system to test how microbiomes from four different primate species - chimpanzees, gorillas, humans and orangutans - change gene regulation in colonic epithelial cells. We found that most host genes respond to microbiomes from different primate species in the same way, but that there are some host genes that have a highly divergent response across different primates, and that these genes are enriched for functional categories related to complex diseases. Finally, we artificially manipulated microbiome communities with a pathogenic strain of Bacteroides fragilis and cultured these communities with colonocytes and colon cancer cell lines in order to explore the link between the gut microbiome and colorectal cancer. We find that specific microbes exert a powerful effect on host gene regulation, but that the strain of B. fragilis had a minor impact on host gene expression in the context of the rest of the gut microbiota. Taken together, this work sheds light on the interaction between gut microbiome composition and host gene regulation and expands our understanding of how the gut microbiome affects host health.