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

Antioxidant micronutrients, including vitamin E, vitamin C, the carotenoids, and selenium, defend the body against free radicals and reactive oxygen molecules, suggesting a potential for these dietary components in cancer prevention. To investigate whether high intakes of antioxidant micronutrients protect against colon cancer in humans, we analyzed data from a prospective cohort study of 35,215 Iowa women aged 55-69 years and without a history of cancer who completed a dietary questionnaire in 1986. Through 1990, 212 incident cases of colon cancer were documented. Adjusted for age, total vitamin E intake was inversely associated with the risk of colon cancer (P for trend < 0.0001); the relative risk for the highest compared to the lowest quintile was 0.32 [95% confidence interval (95% CI) 0.19, 0.54]. Further adjustment for total energy intake and other risk factors in proportional hazards regression had little effect on these estimates. The association was not uniform across age groups: the multivariate relative risk of colon cancer for the highest compared to the lowest quintile of total vitamin E intake was 0.16 (95% CI 0.04, 0.70) for those 55-59 years old, 0.37 (95% CI 0.12, 1.16) for those 60-64 years old, and 0.93 (95% CI 0.27, 3.25) for those 65-69 years old. Multivariate-adjusted relative risks among women with higher total intakes of vitamins A and C and beta-carotene, and among users of selenium supplements, were not significantly different from 1.0. These prospective data provide evidence that a high intake of vitamin E may decrease the risk of colon cancer, especially in persons under 65 years of age.
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PMID:Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. 836 19

We studied the role of reactive oxygen intermediates (ROIs) in experimental liver metastasis induced in mice by the inoculation of COLON 26-M5 murine colon cancer cells, a highly metastatic variant of COLON 26 cells, and the effect of ROIs on the invasive capacity of the cells in an in vitro chemo-invasion assay model using reconstituted basement membrane matrigel. We also measured the release of ROIs from cells using electron spin resonance (ESR) spectrometry. Hydroxyl radicals (.OH) were constitutively released from the cells. This release was augmented by pre-treatment with phorbol 12-myristate 13-acetate (PMA). In experimental liver metastasis in CDF1 mice, the administration of recombinant human superoxide dismutase (r-hSOD) significantly increased the number of metastatic nodules, while administration of catalase significantly inhibited metastasis formation. In vitro pre-treatment of cells with PMA significantly increased the number of metastatic nodules. Invasive capacity of the cells was markedly augmented by pre-treatment with PMA. PMA-induced augmentation was significantly inhibited by the simultaneous addition of r-hSOD to the assay. Catalase had no significant effect. Our findings suggest that ROIs play an important role in tumor invasion and metastasis, and that hydrogen peroxide (H2O2) may contribute to the retention or extravasation of circulating tumor cells. Furthermore, the superoxide anion (O2-) released by tumor cells may play an important role in basement membrane degradation.
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PMID:Effect of reactive oxygen intermediates on the in vitro invasive capacity of tumor cells and liver metastasis in mice. 839 85

There is much evidence suggesting a possible role of reactive oxygen-derived substances in the pathogenesis of both ulcerative colitis and colon cancer. The antioxidant effects of 5-aminosalicylic acid (the active moiety of olsalazine) on induction of colon cancer in an experimental model using 1,2-dimethylhydrazine were studied in male Wistar rats. The levels of reduced glutathione were significantly (P < 0.01) decreased (by approximately 50%) in neoplastic tissues of rats receiving 1,2-dimethylhydrazine alone and olsalazine treatment significantly (P < 0.01) reduced the extent of this alteration. Adjacent tissues from rats receiving either carcinogen alone or carcinogen and olsalazine showed comparable levels of glutathione and these were significantly (P < 0.01) lower than corresponding control values and higher than corresponding values from neoplastic tissues. Activity of the glutathione regenerating enzyme glutathione reductase was significantly (P < 0.01) decreased (by approximately 40%) in neoplastic colonic tissue and this alteration was unaffected by olsalazine treatment. Neither carcinogen nor olsalazine treatment caused alterations in activity of glutathione reductase in adjacent tissue as compared with corresponding control values. Activity of the glutathione utilizing enzyme glutathione peroxidase was significantly (P < 0.01) increased (almost doubled) in neoplastic tissue of rats treated with carcinogen alone. Olsalazine treatment significantly (P < 0.01) reduced the elevation in glutathione peroxidase activity in neoplastic tissues of rats treated with the carcinogen. Glutathione peroxidase showed comparable activity in adjacent tissue from rats treated with either carcinogen alone or a combination of carcinogen and olsalazine and these values were significantly (P < 0.01) lower than corresponding control values. Colonic neoplastic tissues from all experimental groups of animals showed a small, but statistically significant (P < 0.05), decrease in superoxide dismutase activity compared with that in corresponding tissues from control animals.
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PMID:Endogenous antioxidant status in neoplastic and adjacent tissues in 1,2-dimethylhydrazine-induced colon cancer in rats: effects of olsalazine. 864 Sep 47

The present study was performed to investigate processes involved in circumvention of the immune system by advanced stages of tumor growth in the liver. The efficacy of Kupffer cells and pit cells against cancer cells was tested in vivo in an experimental model of colon carcinoma metastasis in rat liver. Liver tumors were induced by administration of CC531 colon cancer cells into the vena portae. After 3 weeks, livers were obtained and partly fixed for electron microscopic procedures or frozen in liquid nitrogen for enzyme and immunohistochemistry at the light microscope level. The activation status of Kupffer cells was studied by expression of Ia-antigen (MHC class II) and by measurement of glucose-6-phosphate dehydrogenase (G6PDH) activity in the cells in situ as a measure of production of reactive oxygen species. Large numbers of Kupffer cells were found in liver parenchyma surrounding colon carcinomas when compared with levels in control livers, but these cells were not activated. Large numbers of activated monocytes and macrophages, cytotoxic T cells but only a few pit cells were found to be recruited to the boundary between liver parenchyma and tumors or their stroma. In those areas where cancer cells invaded liver parenchyma, only newly recruited macrophages and some Kupffer cells were present but few cytotoxic T cells or pit cells were found. The low activation status of Kupffer cells both in terms of production of reactive oxygen species and Ia-antigen expression and the absence of significant numbers of pit cells at tumor sites suggest that Kupffer cells and pit cells do not play a significant role in advanced stages of tumor growth. High levels of prostaglandin E2 were detected in the parenchyma of livers containing tumors and transforming growth factor beta was detected in the stroma of the tumors, therefore suggest that cytotoxicity of newly recruited monocytes, macrophages and cytotoxic T cells may be limited in these stages because of local production of these immunosuppressive factors.
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PMID:Kupffer cells and pit cells are not effective in the defense against experimentally induced colon carcinoma metastasis in rat liver. 887 11

Colorectal cancer is the second most common cause of cancer deaths in the United States for both sexes. Considerable evidence suggests that the risk of this cancer is increased by the mutagenic actions of free radicals, which are produced during oxidation reactions. Dietary factors, the intestinal flora (bacteria), and endogenously produced metabolites contribute to the production of free radicals in the colon. Dietary antioxidants, such as vitamin E, should reduce the levels of these harmful oxidation products. In the absence of vitamin E, polyunsaturated fats can be oxidized in the colon to produce mutagens, such as lipid hydroperoxides and malondialdehyde. Furthermore, fecal bacteria can generate a high flux of reactive oxygen species (e.g., the superoxide radical [O2*-]) at the surface of the intestinal lumen, and inflammatory cells in close proximity to the colon can produce reactive nitrogen species (e.g., nitrogen dioxide [NO2]). Increasing evidence suggests that the different chemical (e.g., alpha- and gamma-tocopherol) and stereochemical (e.g., RRR- and all-racemic-alpha-tocopherol) forms of vitamin E have distinct biologic potencies, pharmacokinetics, and different abilities to prevent neoplastic transformation. This review considers and evaluates recent studies relating vitamin E and oxidative stress to colon cancer, emphasizing the distinct roles of alpha- and gamma-tocopherols. In addition, recent findings on the antioxidant/pro-oxidant status of the digesta (ingested food) are discussed with respect to the use of antioxidants in chemo-prevention trials for colon cancer.
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PMID:Tocopherols and the etiology of colon cancer. 923 Aug 82

Diets high in fat or iron have been associated with an increased risk for development of colon cancer. These two dietary factors are known to decrease manganese superoxide dismutase (MnSOD) activity in colonic mucosa. MnSOD is an antioxidant enzyme that protects mitochondria from oxygen radical damage. MnSOD has tumour suppressive activity and is absent or decreased in most tumours, including those from the colon. This study was designed to determine the effects of high dietary lipid and iron levels on MnSOD activity during the early weeks of colon carcinogenesis. Male Fischer-344 rats were fed 20% lipid diets of either corn oil or menhaden oil containing adequate iron (35 mg/kg) or supplemental iron (535 mg/kg). Rats from each diet were divided into carcinogen treatment groups and given two weekly injections of either azoxymethane (AOM) at a dose of 12 mg/kg, or saline. Mucosal tissue was collected 1, 6 and 12 wk following injections and analysed for MnSOD activity, mineral concentration and nuclear aberrations. Results showed that iron supplementation increased nuclear aberrations, and decreased manganese concentration and MnSOD activity in colonic mucosa ot control animals. AOM, and interaction of iron and AOM, also decreased MnSOD activity. A decrease in the activity of this enzyme during carcinogenesis may be one mechanism whereby these dietary factors ultimately increase tumour risk.
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PMID:Decrease of manganese superoxide dismutase activity in rats fed high levels of iron during colon carcinogenesis. 973 29

The nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and salicylic acid and the short chain fatty acid butyrate are effective colon cancer chemopreventive agents that increase reactive oxygen species (ROS) generation in colon cancer cells. Here we demonstrate that these agents sensitize the normally resistant human HT-29 colon cancer cell line to apoptosis induced by TNF-alpha or a Fas ligating antibody. The role of ROS in this sensitization is supported by the finding that direct exposure of the cells to H2O2 is sufficient for sensitization. Neither TNF-alpha nor Fas ligation alter basal or chemopreventive agent-activated ROS generation, suggesting that the death ligands and chemopreventive agents act in a complementary fashion. The dual chemopreventive agent/death ligand treatments do not increase Fas, TNF receptor 1, Bak or c-myc expression (although salicylic acid moderately induces of Fas expression). Cell death does correlate with alterations in NF-kappa B activity: the NSAIDs, butyrate and H2O2 enhance c-Rel complex formation by TNF-alpha and provide an overall enhancement of NF-kappa B activation by Fas. The antioxidant N-acetylcysteine (NAC) blocks cell death and NF-kappa B activation induced by Fas ligation, suggesting a potential role for NF-kappa B in Fas-induced apoptosis in these cells. The effects of NAC on TNF-alpha-induced cell death are more complex, with NAC being marginally protective and itself enhancing the formation of c-Rel containing complexes at higher concentrations (25 mM). The influence of NSAIDs and butyrate on ROS generation and death ligand sensitivity may be relevant to their ability to suppress colon carcinogenesis.
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PMID:NSAIDs and butyrate sensitize a human colorectal cancer cell line to TNF-alpha and Fas ligation: the role of reactive oxygen species. 999 Feb 95

We review here the oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase (G6PDH) activity to detect cancer cells. This inexpensive and rapid assay can be performed within half an hour. Discrimination between cancerous and noncancerous cells is based on a combination of elevated G6PDH activity, decreased superoxide dismutase (SOD) activity, and decreased lipid peroxidation in cancer cells. The test discriminates between adenomas and carcinomas of the colon with a certainty of >80% and has a high prognostic value for survival of colon cancer patients. Pancreatitis and pancreatic cancer are discriminated with a certainty of 100%. Therefore, the test can be applied by pathologists to provide additional information in difficult cases of diagnosis of cancer and for prognosis.
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PMID:Oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase activity for the discrimination between nonmalignant and malignant cells. 1021 51

Prognosis of colorectal cancer patients that show similar histopathology may vary substantially. An attempt was made to improve prognosis by the self-learning classification program CLASSIF1, based on automated multiparameter analysis of quantitative histochemical and clinical parameters of 64 colorectal carcinomas and adjacent normal mucosae. The histochemical parameters applied were the oxygen-insensitivity assay of glucose-6-phosphate dehydrogenase (G6PDH) activity, a valid discriminator between normal and cancerous mucosae, and related parameters CuZn- and Mn-superoxide dismutase (SOD) levels, and lipid peroxidation (LPO) capacity. Data were processed on the basis of a postoperative follow-up of minimally 32 and maximally 56 months. CLASSIF1 selected the parameters oxygen insensitivity of G6PDH activity, CuZn-SOD and Mn-SOD levels, LPO capacity, lymph node metastasis, Dukes' stage, and age for the highest prognostic value. On the basis of these selected parameters, CLASSIF1 correctly predicted favorable outcome in 100% of the surviving patients and fatal outcome in 64% of the deceased patients. G6PDH activity appeared to be the major information carrier for CLASSIF1. On the basis of G6PDH activity parameters alone, 96% of the surviving patients and 55% of the deceased patients were correctly classified. In comparison, estimation of prognosis on the basis of Dukes' stage alone resulted in 71% correctly classified surviving patients and 61% of patients who died. It is concluded that the self-learning classification program CLASSIF1, on the basis of quantitative histochemical and clinical parameters, is the best prognostic estimator for colon cancer patients yet available.
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PMID:Prognostic estimation of survival of colorectal cancer patients with the quantitative histochemical assay of G6PDH activity and the multiparameter classification program CLASSIF1. 1044 Aug 55

Inactivation of the p53 tumor suppressor protein has been observed in a large number of human cancers. Overexpression of p53 induces either growth arrest or programmed cell death (apoptosis). The growth arrest function of p53 is mediated by induction of p21 (WAF1/CIP1), but the mechanisms underlying p53-dependent apoptosis are still largely unknown. To investigate these mechanisms, we have identified six differentially expressed transcripts in a human colon cancer cell line undergoing p53-dependent apoptosis. One of the p53-responsive genes showed significant homology to Drosophila peroxidasin, an extracellular matrix-associated peroxidase, and is likely to be its human homologue. Our results suggest a possible connection between p53-dependent apoptosis and the production of reactive oxygen species.
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PMID:Isolation of differentially expressed cDNAs from p53-dependent apoptotic cells: activation of the human homologue of the Drosophila peroxidasin gene. 1044 17


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