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

The object of this study was to explore the use of fecal skatole and indole and breath methane and hydrogen as metabolic markers of the anaerobic colonic flora in patients with unresected large bowel cancer or polyps. Patients with descending or sigmoid colon cancer were more likely to be breath methane excretors than control subjects, patients with proximal colon cancer, and patients with rectal cancer. Control subjects excreting breath methane excreted less fecal skatole than breath methane excretors in the following groups: patients with adenomatous polyps, all patients with colorectal cancer, patients with proximal colon cancer, patients with descending and sigmoid colon cancer, and patients with rectal cancer. These data suggest that fecal skatole excretion equal to or greater than 100 micrograms/g feces might be useful to discriminate colorectal cancer patients from control subjects. Twenty-nine percent (8 of 28) of the cancer patients had both "high" skatole levels and breath methane excretion compared with only 2% (1 of 41) of the control subjects (P less than 0.01).
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PMID:Fecal skatole and indole and breath methane and hydrogen in patients with large bowel polyps or cancer. 398 May 62

The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent and cAMP-independent kinase activities were measured in the 1,2-dimethylhydrazine (DMH) induced rat colon cancer and in untreated colon. Previous studies had shown that intestinal tumors induced by chronic exposure to DMH contained 2-fold less intracellular cAMP. The present findings indicate that reduction in cAMP-dependent protein kinase activities also occur in colon cancer cells. Similar hydrogen ion dependence (pH 6-7) and approximate association constants (Ka approximately 0.1 microM) were observed for the enzymes existing in both normal and tumor tissues, while the cAMP-dependent tumor protein kinase was found to phosphorylate phosvitin and casein to a greater degree. These recent findings are consistent with the concept that the concentrations of cAMP and activities of its associated enzyme system are inversely related to the cell proliferation state.
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PMID:Adenosine 3',5'-cyclic monophosphate dependent and independent protein kinase activities in 1,2-dimethylhydrazine induced rat colon cancer. 628 71

Breath hydrogen and methane are specific end products of colonic fermentation, a process which may play a protective role against colon cancer. To assess the possibility of using these markers in epidemiological studies, we characterized the intra- and intersubject variability of breath hydrogen and methane excretion over 15 consecutive days among 32 men and women of various ethnic backgrounds (16 Asians, 8 Caucasians, 8 Hawaiians). Participants were asked to collect four end-expiratory samples each day, which we had shown previously would optimally characterize daily hydrogen excretion. There was substantial within-subject variation in breath hydrogen over the study, although breath methane levels were more constant over time. We found that about 4 days of measurement of breath hydrogen and 1 day of measurement for breath methane are required to correctly characterize individuals according to their long-term excretion of these gases. This was true for Asians and non-Asians. Although breath methane appears to be more practical to measure, it is a less sensitive marker of colonic fermentation than breath hydrogen. Whereas all subjects excreted hydrogen, only 28% of the subjects excreted methane, and methane excretor status of a few participants varied during the study. Because the breath test is noninvasive and reliable, we tested the multiple day collection protocol among colon cancer patients and controls and found it to be well accepted. We conclude that it is practical to measure breath hydrogen and methane in large epidemiological studies conducted at the individual level. The potential use for these markers is discussed.
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PMID:Use of breath hydrogen and methane as markers of colonic fermentation in epidemiological studies: variability in excretion. 804 36

Resistant starch is by definition that part of starch that escapes digestion in the small bowel. Cecal fermentation of resistant starch into short-chain fatty acids will result subsequently in a decrease in pH. Thus, resistant starch may have the same effect on colonic luminal contents and mucosa as some fiber components. We studied the effects of adding 45 g native amylomaize (Hylon-VII) to a standardized diet in 14 healthy volunteers on fermentation and colonic mucosal proliferation. Hylon-VII is a high amylose maize starch, containing 62% resistant starch. During amylomaize consumption, breath hydrogen excretion rose 85% and fecal short chain fatty acid output increased 35% (P < 0.01). Excretion of primary bile acids increased and the soluble deoxycholic acid concentration decreased by 50% (P = 0.002). Subsequently, cytotoxicity of the aqueous phase of feces--as measured on a colon cancer cell line--decreased (P = 0.007). Colonic mucosal proliferation in rectal biopsies (proliferating cell nuclear antigen immunostaining) decreased from 6.7 to 5.4% (P = 0.05). We speculate that resistant starch consumption decreases colonic mucosal proliferation as a result of the decreased formation of cytotoxic secondary bile acids, which is possibly mediated through acidification of the large bowel by production of short-chain fatty acids.
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PMID:Effect of resistant starch on colonic fermentation, bile acid metabolism, and mucosal proliferation. 814 50

Neovascularization and hemorrhage are common features of malignant tumors. We wondered whether hemoglobin derived from extravasated RBC deposits heme-derived iron into the tumor, which could modulate the sensitivity of cancer cells to oxidant-mediated injury. A brief exposure (1 h) of 51Cr-radiolabeled breast cancer cells (BT-20) but not colon cancer cells (Caco-2) to hemin (10 microM) or FeSO4 (10 microM) significantly enhances cytotoxicity mediated by 0.5 mM hydrogen peroxide (H2O2). Associated with Caco-2 resistance, these cells were found to be enriched in the endogenous iron chelator, ferritin. If cellular ferritin is even further increased through 1 h incubation (24 h prior to H2O2 exposure) of both cell types with hemin, FeSO4, or exogenous spleen apoferritin itself (24 h), marked resistance to H2O2-mediated cytotoxicity is manifest. Under several conditions, the sensitivity of tumor cells to oxidant-mediated lysis is inversely proportional to their ferritin content. Pretreatment of BT-20 and Caco-2 cells with hemin or FeSO4 rapidly increases H-ferritin mRNA but only slightly increases L-ferritin mRNA; nevertheless, large increases in overall ferritin content of iron-exposed cells result. Data analogous to those with H2O2-mediated cytotoxicity were obtained in studies of bleomycin-engendered DNA strand breakage and cell damage, i.e., brief treatment of BT-20 cells with both hemin or FeSO4 significantly increases their sensitivity to bleomycin (100 micrograms/ml), whereas treatment followed by 24 h incubation with media alone significantly protects against bleomycin toxicity. We speculate that acute exposure of tumors to iron (e.g., derived from heme-proteins in hemorrhagic cancerous lesions) may increase sensitivity of some cancer cells, particularly those relatively low in endogenous ferritin, to oxidant-mediated lysis. In contrast, repeated, more chronic, exposure effector cells or chemotherapeutic agents, an effect derived from their increased synthesis and accumulation of the intracellular iron scavenger, ferritin.
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PMID:Tumor cell heme uptake induces ferritin synthesis resulting in altered oxidant sensitivity: possible role in chemotherapy efficacy. 822 66

Results from laboratory and clinical studies have suggested that fermentation in the large bowel may play a protective role against colon cancer. Hydrogen and methane are end-products of colonic fermentation that are absorbed into the bloodstream and excreted via expired air in the breath. Thus, breath levels of hydrogen and methane have been used as markers for this process. Breath levels of these gases were compared among 10 ethnic and sex groups that exhibit marked differences for colon cancer risk in Hawaii. Four end-expiratory breath samples were used to characterize daily excretion of hydrogen and methane in a population-based sample of 244 men and women. There was no significant difference in breath hydrogen or methane by sex or age. Hawaiians produced significantly more hydrogen than Filipinos, and Hawaiians and Caucasians more methane than the 3 Asian groups. These differences did not correlate with risk of colon cancer among these ethnic populations.
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PMID:Breath hydrogen and methane in populations at different risk for colon cancer. 825 24

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

Since the metabolic activity of the colonic flora plays a definite role in colon cancer and an increased incidence of this disease is reported after cholecystectomy, we studied the metabolic activity of the colonic flora in a group of postcholecystectomy patients and matched controls by measuring, as representative end products of the bacterial metabolism, their fecal bile acids (BA), fecal 3-methylindole (SK) and indole (IN), and respiratory methane and hydrogen. Patients had significantly higher SK and lower IN, and, among BA, higher lithocholic (LCA) and chenodeoxycholic acid concentrations and LCA/deoxycholic acid ratio in the stools than controls. Similar differences from controls were reported for colon cancer. Comparable bacterial metabolic activities are thus operative in the large bowel of postcholecystectomized and colon cancer patients. This supports the biological plausibility of the association of cholecystectomy and colon cancer.
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PMID:Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy. 844 84

Protein tyrosine phosphatases (PTPases) play an important role in regulating cell growth and transformation. We report that the antitumor agent gallium nitrate is a potent inhibitor (concentration producing 50% inhibition, 2-6 microM) of detergent-solubilized cellular membrane PTPase from Jurkat human T-cell leukemia cells and HT-29 human colon cancer cells. This is the first report of a selective, small molecule drug inhibitor of PTPase. Gallium nitrate did not inhibit CD45, a PTPase found in the membranes of hemopoietic lineage cells such as Jurkat cells. Studies with gallium nitrate and a series of gallium-containing analogues revealed no correlation between growth-inhibitory activity in Jurkat and HT-29 cells and the ability to inhibit detergent-solubilized PTPase. Gallium nitrate and most of the gallium analogues penetrate poorly into cells. In contrast, a gallium-hydrogen peroxide complex inhibits DNA synthesis in Jurkat cells and induces the accumulation of phosphotyrosines on multiple intracellular proteins in this cell line. Gallium-hydrogen peroxide complex and gallium nitrate have similar inhibitory activity toward detergent-soluble PTPase. This is a new mechanism of action for gallium nitrate but it is not known if the inhibition of PTPase is related to the antitumor activity of gallium nitrate.
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PMID:Inhibition of protein tyrosine phosphatase by the antitumor agent gallium nitrate. 846 6

A number of oligonucleotides were designed to bind through Hoogsteen triple helix or Watson-Crick hydrogen bonds to the p53 consensus sequence homology localized within the human nontranscribed rRNA spacer region. The oligomers, which bind in vitro to the consensus sequence homology, function as p53 analogues in cells deficient in wild-type p53 protein. Oligomers suppress proliferation of human colon cancer cells by three to eightfold, but only suppress proliferation of normal human mesangial cells or lung fibroblasts by less than 50%. On the basis of these studies, p53 analogues may be used therapeutically to selectively modify proliferation of transformed cells.
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PMID:Suppression of cellular proliferation using p53 DNA recognition site-related oligonucleotides. 861 76


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