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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caudal type homeobox gene-1 and -2 (CDX-1 and CDX-2), homologues of the Drosophila homeobox gene caudal, encode transcription factors in endoderm derived tissues of the intestine. CDX genes control proliferation and differentiation of intestinal mucosal cells and colon cancer cells. Hirschsprung's Disease (HD) or congenital intestinal aganglionosis, a major developmental anomaly of intestine, which causes functional intestinal obstruction, is frequently associated with enterocolitis. Aetiology of HD-associated enterocolitis (HDEC) remains obscure. Reduction of gut mucosal enteroendocrine cells, and inefficient transfer of the secretory immunoglobulin A across the gut mucosal cell were shown to be associated with enterocolitis in HD patients suggesting that mucosa may directly involve in the pathophysiology of HDEC. This study aims to ascertain whether the CDX-1 and CDX-2 genes, that control the proliferation and differentiation of mucosal cells, play a role in HDEC. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridisation, we analysed the expression of CDX-1 and CDX-2 genes in colon specimens of normal controls, necrotising enterocolitis (NEC) infants, and HD patients with and without enterocolitis. We showed for the first time that CDX-1 and CDX-2 genes were expressed in the colonic mucosal epithelium in normal, NEC and in HD infants. However, the expressions of both genes were reduced in patients with HDEC. Our findings suggest that reduced expression of CDX-1 and CDX-2 genes in mucosa may be associated with the development of HDEC.
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PMID:CDX-1 and CDX-2 are expressed in human colonic mucosa and are down-regulated in patients with Hirschsprung's disease associated enterocolitis. 1156 52

About 5% of colon cancer cases correspond to classic hereditary monogenic mendelian transmission involving at least 8 major genes of predisposition to this tumor. Genes with more moderate effects, in association with other genes can contribute to the occurrence of sporadic polygenic forms. These genes confer susceptibility to environmental factors and can play the role of aggravating or protective modifier genes in the different hereditary forms. Foods can interact with these genes and modulate their expression. Moreover sequence variations (polymorphisms) in these genes may also be responsible for slower or more rapid metabolism of nutrients leading to toxic or carcinogenic compounds. If some foods, or "pharmafoods" can have beneficial effects in some individuals with a particular subtype of the disease, others can be inefficient or even detrimental in patients with the same disease but with a different genetic origin or if the genetic background is different. Moreover tumorigenic processes are diverse. Tumor progression depends on genetic and environmental factors different from tumor initiation and on the site of the tumor along the colon tract. Interactions with the gut flora, the lymphoid system and specific features of growth of the colon mucosa are also important parameters. Today with a formidable genetic knowledge arising from the genome project, new epidemiological data integrating the genetic data for multiple markers and a better knowledge of the tumorigenic processes involved, a new discipline is emerging. "Nutrigenetics" which is the study of hereditary basis of individual variations in response to foods opens for the oncoming decade the era of a personalised predictive medecine based on a nutrition adapted to the genetic make up of each of us.
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PMID:[Colon cancer and nutritional genetics: modifier genes]. 1159 47

1. Nonsteroidal anti-inflammatory drug (NSAID) usage is associated with gastrointestinal inflammatory damage and aggravation of gut inflammatory conditions. NSAIDs also exert a preventive effect against colon cancer that seems to be due to increased colon cell apoptosis. NSAIDs have been shown to modulate the release of colony stimulating factors (CSFs) in some cells. In the present study we analysed the effect of these drugs on secretion of CSFs and apoptosis in human colon epithelial cells (HT-29). 2. HT-29 cells secreted bioactive levels of GM-CSF, G-CSF and M-CSF when stimulated with IL-1ss and TNF-alpha, and diclofenac (10(-7)-10(-4) M), indomethacin (10(-7)-10(-4) M) and sodium salicylate (10(-5)-10(-2) M) induced concentration-dependent increases in GM-CSF secretion. 3. Reduced secretion of G-CSF and M-CSF and increased cell apoptosis were observed with the highest concentrations of these non-selective NSAIDs. 4. No changes in any CSF release or HT-29 cell apoptosis were detected in the presence of the COX-2 selective inhibitor DFP (10(-7)-10(-4) M). 5. Neither the exogenous addition of CSFs nor the blockade of secreted CSFs modified apoptosis in HT-29 cells stimulated with cytokines and/or NSAIDs. 6. These results suggest that colon epithelial cells can contribute to local inflammatory responses by releasing CSFs and thus extend the life span of local leukocytes. Modulation of CSF levels by non-selective NSAIDs may be involved in the pro-inflammatory effects of these agents in the gut.
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PMID:Relationship between endogenous colony stimulating factors and apoptosis in human colon cancer cells: role of cyclo-oxygenase inhibitors. 1170 43

Curcumin, the yellow pigment in turmeric, prevents malignancies in the intestinal tract of rodents. It is under clinical evaluation as a potential colon cancer chemopreventive agent. The systemic bioavailability of curcumin is low, perhaps attributable, at least in part, to metabolism. Indirect evidence suggests that curcumin is metabolized in the intestinal tract. To investigate this notion further, we explored curcumin metabolism in subcellular fractions of human and rat intestinal tissue, compared it with metabolism in the corresponding hepatic fractions, and studied curcumin metabolism in situ in intact rat intestinal sacs. Analysis by high-performance liquid chromatography, with detection at 420 or 280 nm, permitted characterization of curcumin conjugates and reduction products. Chromatographic inferences were corroborated by mass spectrometry. Curcumin glucuronide was identified in intestinal and hepatic microsomes, and curcumin sulfate, tetrahydrocurcumin, and hexahydrocurcumin were found as curcumin metabolites in intestinal and hepatic cytosol from humans and rats. The extent of curcumin conjugation was much greater in intestinal fractions from humans than in those from rats, whereas curcumin conjugation was less extensive in hepatic fractions from humans than in those from rats. The curcumin-reducing ability of cytosol from human intestinal and liver tissue exceeded that observed with the corresponding rat tissue by factors of 18 and 5, respectively. Curcumin sulfate was identified in incubations of curcumin with intact rat gut sacs. Curcumin was sulfated by human phenol sulfotransferase isoenzymes SULT1A1 and SULT1A3. Equine alcohol dehydrogenase catalyzed the reduction of curcumin to hexahydrocurcumin. The results show that curcumin undergoes extensive metabolic conjugation and reduction in the gastrointestinal tract and that there is more metabolism in human than in rat intestinal tissue. The pharmacological implications of the intestinal metabolism of curcumin should be taken into account in the design of future chemoprevention trials of this dietary constituent.
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PMID:Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. 1181 7

Probiotics are defined as live microorganisms of human origin. Their use may favorably influence human health and ameliorate or prevent certain diseases. Prebiotics are non-digestible foodstuffs (fiber, oligofructans - "colonic foods"), which enter the colon and are metabolized by the probiotics. Probiotics should fulfill the following criteria: Phenotypic and genotypic classification, no pathogenic properties, human origin, application in the living state, resistance to gastric acid and bile, ability to adhere to colonocytes, ability to colonize the gut, clinically proved favorable health-effect, and safety. Experimental and clinical studies supplied evidence of the possible use of probiotics in the following diseases: Traveler's diarrhea, antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, infantile diarrhea, rotavirus enteritis, inflammatory bowel disease, irritable bowel syndrome, colon cancer, peritonitis, acute pancreatitis, and diarrhea associated with HIV infection. Probiotics displayed the following effects in these studies: Involvement in production of essential nutrients of the colonic mucosa, beneficial effect on intestinal immunity, recovery of the disturbed gut mucosal barrier and prevention of microbial translocation, elimination of toxins and eradication of microbial pathogens, production of steroids from cholesterol and reduction of its pool in circulation, participation in regulation of intestinal functions, reduced incidence of chemically induced colon tumors in rodents. Probiotics open new therapeutic modalities in a number of diseases and it may be expected that their importance will increase with growing knowledge and experience.
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PMID:[Probiotics in gastroenterology]. 1190 55

The potential 'nutritional advantages' of probiotics and prebiotics consist of preventive, and sometimes curative, effects against certain diseases. The evidence supporting such advantages, which requires randomised controlled trials and consistency of results from study to study, is rapidly increasing. This article summarizes the effects against diseases of intestinal origin. There is a high level of evidence for positive effects of some prebiotics to alleviate constipation and treat hepatic encephalopathy. Interesting aspects, but with a lower level of evidence at the present time, include prevention of colon cancer, intestinal infection, and recurrence of inflammatory bowel disease. There is a high level of evidence for positive effects of some probiotics in the alleviation of lactose intolerance, antibiotic-associated intestinal disorders and gastroenteritis. Evidence is rapidly growing regarding the prevention of recurrence of inflammatory bowel diseases. Positive trials have suggested preventive effects against intestinal colonization with specific gut pathogens including Clostridium difficile and Helicobacter pylori.
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PMID:Nutritional advantages of probiotics and prebiotics. 1208 12

Inulin is extracted from the chicory root. It is a set of fructans with its monomers linked by means of beta(2-1) bonds. This linkage cannot be hydrolysed by either pancreatic or by brush border digestive enzymes in the upper intestinal tract of humans. As such the carbohydrates arrive in the colon, where they are fermented by bifidobacteria and other lactic acid producing bacteria, thus enhancing their relative populations in the gut. Recent research in experimental animal models revealed that inulin has significant anticarcinogenic properties. It acts chemopreventively by reducing the incidence of azoxymethane (AOM) - induced aberrant crypt foci and tumours in the colon. These effects may be due to the stimulation of bifidobacteria, which themselves have been shown to act as antigenotoxic in the colon and to reduce AOM-induced tumours. Also fermentation products, including the short-chain fatty acid butyrate, could contribute to the protective effects. In this case a mechanism may be the induction of apoptosis of already transformed cells. The experimental evidence from animal studies and from studies elucidating potential mechanisms strongly supports the possibility that inulin will contribute to reducing risks for colon cancer in humans. In order to obtain more insight into this possibility, human dietary intervention studies relating biomarkers of reduced risk to inulin consumption are needed.
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PMID:Experimental evidences on the potential of prebiotic fructans to reduce the risk of colon cancer. 1208 29

The intestinal mucosa is a rapidly-renewing tissue characterized by cell proliferation, differentiation, and eventual apoptosis with progression up the vertical gut axis. The inhibition of phosphatidylinositol (PI) 3-kinase by specific chemical inhibitors or overexpression of the lipid phosphatase PTEN enhances enterocyte-like differentiation in human colon cancer cell models of intestinal differentiation. In this report, we examined the role of PI 3-kinase inhibition in the regulation of apoptotic gene expression in human colon cancer cell lines HT29, HCT-116, and Caco-2. Inhibition of PI 3-kinase with the chemical inhibitor wortmannin increased TNF-related apoptosis-inducing ligand (TRAIL; Apo2) mRNA and protein expression. Similarly, overexpression of the tumor suppressor protein PTEN, an antagonist of PI 3-kinase signaling, resulted in the increased expression of TRAIL. Activation of PI 3-kinase by pretreatment with IGF-1, a gut trophic factor, markedly attenuated the induction of TRAIL by wortmannin. Moreover, overexpression of active Akt, a downstream target of PI 3-kinase, or inhibition of GSK-3, a downstream target of active Akt, completely blocked the induction of TRAIL by wortmannin. Consistent with findings that TRAIL is induced by agents that enhance intestinal cell differentiation, TRAIL expression was specifically localized to the differentiated cells of the colon and small bowel. Adenovirus-mediated overexpression of TRAIL increased DNA fragmentation of HCT-116 cells, demonstrating the functional activity of TRAIL induction. Taken together, our findings demonstrate induction of the TRAIL by inhibition of PI 3-kinase in colon cancer cell lines. These results identify TRAIL, a novel TNF family member, as a downstream target of the PI 3-kinase/Akt/GSK-3 pathway and may have important implications for better understanding the role of the PI 3-kinase pathway in intestinal cell homeostasis.
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PMID:Regulation of TRAIL expression by the phosphatidylinositol 3-kinase/Akt/GSK-3 pathway in human colon cancer cells. 1214 Feb 94

Dietary oxidants like lipid hydroperoxides (LOOH) can perturb cellular glutathione/glutathione disulphide (GSH/GSSG) status and disrupt mucosal turnover. This study examines the effect of LOOH on GSH/GSSG balance and phase transitions in the human colon cancer CaCo-2 cell. LOOH at 1 or 5 micro m were noncytotoxic, but disrupted cellular GSH/GSSG and stimulated proliferative activity at 6 h that paralleled increases in ornithine decarboxylase activity, thymidine incorporation, expression of cyclin D1/cyclin-dependent kinase 4, phosphorylation of retinoblastoma protein, and cell progression from G0/G1 to S. At 24 h, LOOH-induced sustained GSH/GSSG imbalance mediated growth arrest at G0/G1 that correlated with suppression of proliferative activity and enhanced oxidative DNA damage. LOOH-induced cell transitions were effectively blocked by N-acetylcysteine. Collectively, the study shows that subtoxic LOOH levels induce CaCo-2 GSH/GSSG imbalance that elicits time-dependent cell proliferation followed by growth arrest. These results provide insights into the mechanism of hydroperoxide-induced disruption of mucosal turnover with implications for understanding oxidant-mediated genesis of gut pathology.
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PMID:Lipid peroxide-induced redox imbalance differentially mediates CaCo-2 cell proliferation and growth arrest. 1215 14

Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS). The aim of the study was to determine whether physiological ferric/ferrous iron induces oxidative DNA damage in human colon cells. Therefore, differentiated human colon tumour cells (HT29 clone 19A) were incubated with ferric-nitrilotriacetate (Fe-NTA) or with haemoglobin and DNA breaks and oxidised bases were determined by microgelelectrophoresis. The effects of Fe-NTA were measured with additional H(2)O(2) (75microM) and quercetin (25-100microM) treatment. Analytic detection of iron in cell cultures, treated with 250microM Fe-NTA for 15 min to 24h, showed that 48.02+/-5.14 to 68.31+/-2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000microM) induced DNA breaks and oxidised bases, which were enhanced by subsequent H(2)O(2) exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H(2)O(2) for 15 min, 37 degrees C did not change the effect of H(2)O(2) alone. The impact of Fe-NTA and H(2)O(2)-induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H(2)O(2)-control). Haemoglobin was as effective as Fe-NTA in inducing DNA damage. From these results we can conclude that iron is taken up by human colon cells and participates in the induction of oxidative DNA damage. Thus, iron or its capacity to catalyse ROS-formation, is an important colon cancer risk factor. Inhibition of damage by quercetin reflects the potential of antioxidative compounds to influence this risk factor. Quantitative data on the genotoxic impact of ferrous iron (e.g. from red meat) relative to the concentrations of antioxidants (from plant foods) in the gut are now needed to determine the optimal balance of food intake that will reduce exposure to this type of colon cancer risk factor.
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PMID:Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A. 1216 Sep


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