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

The role which the human colon fulfils in digestion and metabolism remains largely undocumented. Its capacity to conserve water and electrolytes is well known although how this is controlled is uncertain. In the animal kingdom, calcium and magnesium absorption from the colon are improtant as are absorption and synthesis of vitamins. The abundant microflora of the human colon gives it unique properties. Dietary residue is metabolised forming short-chain fatty acids, hydrogen, carbon dioxide and methane; whilst 20% of urea synthesised in man is broken down in the colon to ammonia, which is reabsorbed, and carbonic acid. The microflora also degrades a wide variety of organic compounds including food additives, drugs, bile salts, and cholesterol which may be relevant to the development of colon cancer. Regional differences in colonic function also exist making interpretation of data from this relatively inaccessible organ more difficult.
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PMID:The colon: Absorptive, seccretory and metabolic functions. 120 9

The results of three small clinical trials examining the effect of calcium carbonate supplementation on the proliferation cytokinetics of the rectal epithelium in subjects with a current history of sporadic adenoma are reported. In six subjects, a daily administration of 1500 mg of calcium carbonate for 90 days failed to significantly suppress thymidine labeling in normal-appearing mucosa of the rectum. However, a daily dose of 2000 mg of calcium significantly (P = 0.008) altered mucosal proliferation in a second set of six subjects after a 30-day trial. Finally, a placebo-controlled trial of calcium (2000 mg) was conducted in which 20 subjects were randomized to groups receiving a 4-week intervention with calcium (or placebo), followed by the alternative treatment (placebo or calcium). The results of the study show a marked suppression of rectal proliferation during the calcium phase of the study but not during the placebo phase. This study adds to accumulating evidence showing that calcium supplementation regulates the proliferative behavior of colonic epithelium in the individual at high risk for colon cancer. Longer term trials of calcium supplementation will ascertain whether a continuing benefit from increasing dietary calcium translates into inhibition of adenoma recurrence.
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PMID:Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma. 129 28

Changes in cytosolic free Ca2+ ([Ca2+]i) in response to the secretagogue carbachol have been characterized in the human colon cancer cell line T84, a model Cl- secretory cell. In this study, [Ca2+]i was determined with the fluorescence indicator fura-2 at the single-cell level with a fluorescent microscope-imaging system. Basal [Ca2+]i in T84 cells in Ringer-HCO3 solution was 76 +/- 4 nM and was decreased by exposure to Ca2+ free solution or 25 microM verapamil. The cholinergic agonist carbachol caused a concentration-dependent rise in [Ca2+]i with a Km of 4 microM and a peak increase in [Ca2+]i of approximately 50 nM. The onset of the [Ca2+]i increase was within 3 s, occurred uniformly among cells, and peaked at 10-15 s. The increase in [Ca2+]i was heterogenous in the length of time the [Ca2+]i remained elevated above basal, and cell responses could be divided into at least two groups on that basis. Blocking the contributions of intracellular Ca2+ with dantrolene inhibited the increase in [Ca2+]i as early as could be determined, whereas blocking the extracellular contribution with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), verapamil, or nifedipine inhibited a slightly later increase in [Ca2+]i. In conclusion, the initial detectable increase in [Ca2+]i caused by carbachol is due to the release of Ca2+ from internal stores, whereas the contribution of extracellular Ca2+ occurs later and at least partially involves a nifedipine- and verapamil-sensitive process.
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PMID:Carbachol-induced cytosolic free Ca2+ increases in T84 colonic cells seen by microfluorimetry. 251 1

Two in vivo and one in vitro studies were performed to evaluate the chemoprotective role of calcium during the early period of azoxymethane (AOM) induction. In the first set of experiments, groups of male Fischer 344 rats were s.c. injected with either AOM (20 mg/kg) or water (controls) and sacrificed immediately (0 time), and 1, 3, 5, and 7 days postinjection. In the second set of experiments, animals were injected with the same dose of AOM and subsequently pair-fed with rat chow containing either calcium carbonate or diet devoid of added calcium. The amount of calcium consumed was calculated to be 250 mg/kg b.w. In both experiments, colonic mucosa was assayed for ornithine decarboxylase (ODC). In addition, tyrosine kinase (Tyr-k) activity as well as tyrosine specific phosphorylation of membrane proteins were determined. Results revealed that maximal stimulation by AOM of ODC and Tyr-k activity occurred 5 days postinjection. This stimulation was significantly suppressed by calcium. AOM also produced an increase in the rate of tyrosine specific phosphorylation of two distinct colonic mucosal membrane proteins with Mr of 57,000 and 59,000. Again, dietary calcium suppressed the stimulation. In the third set of experiments, organ culture was utilized. Methylazoxymethanol, the active metabolite of AOM, was used instead of AOM in this part of the study. Four hour exposure of mucosal explants to methylazoxymethanol (1 microgram/ml) resulted in a significant (20-30%) increase in ODC and Tyr-k activity when compared to controls. Addition of either CaCl2 (2 mumol/ml) or difluoromethylornithine (2 nmol/ml) the irreversible inhibitor of ODC, significantly suppressed the methylazoxymethanol-induced activity of both ODC and Tyr-k. We conclude that calcium may have a chemoprotective role and tyrosine kinases may have a regulatory role in the early stages of AOM induction of colon cancer.
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PMID:Attenuation of azoxymethane-induced colonic mucosal ornithine decarboxylase and tyrosine kinase activity by calcium in rats. 279 Aug 2

This investigation was based on an epidemiologic association of milk consumption and decreased intestinal cancer risk. Furthermore, there is also some indirect evidence that calcium supplementation in humans and animals may decrease colon cancer risk and that calcium, by inference, may be the protective factor in milk. In order to investigate these associations in a controlled laboratory setting, dietary supplementation of low fat dried milk (37 g/kg diet; N = 18) and calcium carbonate (40 mg/kg rat/day; N = 17) were compared separately to regular diet controls in the rat-dimethylhydrazine colon carcinogenesis model. The results of this investigation showed that neither milk-supplemented rats nor calcium carbonate-supplemented rats had fewer DMH-induced colorectal (P = .374) or total gastrointestinal tumors (P = .291) than did regular diet controls (N = 10; by analysis of variance [ANOVA]). Milk supplementation did result in a significant decrease in tumor burden when measured by incidence of metastases (P = .035) and of intestinal obstruction (P = .011; by chi-square test), when compared with calcium-supplemented and control rats. Though this implies that milk supplementation provides protection against some aspects of carcinogenesis of the colon, in rats fed low fat diets, this does not appear to be mediated through the calcium content of milk.
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PMID:The effect of dietary milk and calcium on experimental colorectal carcinogenesis. 369 Dec 67

We studied the frequency and distribution of proliferating epithelial cells lining colonic crypts in 10 subjects at high risk for familial colonic cancer, before and after oral supplementation of their conventional diets with 1.25 g of calcium as calcium carbonate. Patterns of cell proliferation were defined by dividing the colonic crypt into longitudinal compartments and comparing the numbers and fractions of tritiated thymidine--labeled epithelial cells in the various compartments. Before dietary supplementation with calcium, the profile of proliferating epithelial cells in the colonic crypts was comparable to that previously observed in subjects who had had familial colonic cancer. Two to three months after supplementation had been started, proliferation was significantly reduced and the profile of the colonic crypts approached that previously observed in subjects at low risk for colonic cancer. Our findings indicate that oral calcium supplementation induces a more quiescent equilibrium in epithelial-cell proliferation in the colonic mucosa of subjects at high risk of colon cancer, similar to that observed in subjects at low risk.
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PMID:Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. 405 32

Oral calcium supplementation is thought to be a useful interventional agent to decrease colon cancer risk. This is supposedly due, at least in part, to the binding of bile acids and fatty acids by calcium in the colon, thus prohibiting the damaging effects of these substances to the epithelium. To determine the effects of calcium supplementation on fecal fat excretion, 24 subjects kept a fat and calcium constant diet for one week and were supplemented with either 0, 2 or 4 g elemental calcium as calcium carbonate in a double-blind fashion. At the end of the week 72-hour feces was collected, and total fat, neutral fat, fatty acids and the ratio of polyunsaturated and saturated fatty acids (P/S ratio) were measured. Calcium dose-dependently increased the percentual excretion of total fat as related to fat intake: 6.8 +/- 0.9% during 0 g, 7.4 +/- 1.0% during 2 g and 10.2 +/- 1.4% during 4 g, r = 0.44, p = 0.03. This was due to increased fatty acid excretion, excretion of neutral fat was not affected, nor was the P/S ratio. It is concluded that calcium supplementation modestly increases fecal fatty acid excretion. No adverse metabolic effects are to be expected from this in case of long-term calcium supplementation in subjects at increased risk for colon cancer.
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PMID:Effects of supplemental dietary calcium on quantitative and qualitative fecal fat excretion in man. 783 78

Foci of aberrant and/or hexosaminidase-negative crypts in rat colon are putative precancerous lesions that have been proposed as biomarkers for short-term bioassays for chemical carcinogens and chemopreventive agents. The ability of a substance to reduce the yield of azoxymethane (AOM)-induced foci in the colon of male Fischer 344 rats, was evaluated as a screening assay for chemopreventive agents. Twenty-eight test agents were administered continuously in the diet from the start of the experiments until the animals were killed 35 days later. AOM was s.c. administered either as 15 mg/kg body wt on days 7 and 14 or as 30 mg/kg body wt on day 7 of the experiment. Foci of aberrant crypts were evaluated in whole mounts of methylene blue-stained colons. AOM induced twice as many foci when administered between 8.40 and 11.00 a.m. than between 2.45 and 5.55 p.m. Calcium salts of carbonate, chloride and glucarate decreased the yield of AOM-induced foci while the acidic salts of lactate and phosphate did not inhibit the formation of foci. Dimethyl-fumarate, fumaric acid, genistein, piroxicam, simethicone, sodium suramin and sulindac reduced the yield of AOM-induced foci of aberrant crypts, with genistein being the most potent. Only piroxicam of this group has previously been shown to inhibit colon cancer, while the rest have yet to be evaluated. Ibuprofen did not inhibit the formation of foci, although it has been reported to inhibit AOM-induced colon cancer in rats. Piroxicam and sulindac appeared to reduce preferentially hexosaminidase-negative foci of aberrant crypts, compared with those of apparently normal morphology. The AOM-induced foci of aberrant crypts assay appears suitable for screening chemicals for chemopreventive action.
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PMID:Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. 820 67

Recently we have shown that supplemental dietary calcium precipitates luminal cytolytic surfactants and thus inhibits colonic epithelial proliferation, which may decrease the risk of colon cancer. In Western diets, milk products are quantitatively the most important source of dietary calcium. However, they also contain large amounts of phosphate, which has been hypothesized to inhibit the antiproliferative effect of calcium. Therefore, we studied in rats the possible differential antiproliferative effects of dairy calcium, calcium carbonate, and calcium phosphate, supplemented to a Western high-risk control diet. We observed that fecal bile acid excretion was similar in the various diet groups, whereas fatty acid excretion was stimulated by the calcium supplements in the order calcium carbonate > calcium phosphate > milk mineral. In fecal water, concentrations of bile acids and fatty acids were drastically decreased in the supplemented groups, resulting in decreased cytolytic activity of fecal water. In vitro incubation of fecal water from the control group with insoluble calcium phosphate also decreased the high concentrations of surfactants and their cytolytic activity. The response of the colonic epithelium to these primary luminal effects of calcium was a decrease in cell damage and cell proliferation. Only minor differences between the supplements were observed. The concentration of serum gastrin, the possible trophic effect of which could counteract the antiproliferative effect of calcium, was increased by the supplements, but no significant correlation was observed between serum gastrin concentration and epithelial proliferation. We conclude that dietary calcium precipitates luminal surfactants and thus inhibits cytolytic activity, epithelial cell damage, and colonic proliferation. The similar efficacy of calcium carbonate, calcium phosphate, and milk mineral indicates that the antiproliferative effect of milk mineral is mediated by its calcium content and is not inhibited by phosphate.
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PMID:Mechanism of the antiproliferative effect of milk mineral and other calcium supplements on colonic epithelium. 826 69

This study sought to produce monoclonal antibodies (MAbs) which reacted with the MUC2 core protein. Two MAbs [3A2 (IgG1) and 4F1 (IgM)] were produced by immunising female BALB/c mice with gel-formed mucin from the LS174T colon cancer cell line followed by a KLH conjugate of a 29 amino acid synthetic peptide whose sequence was derived from the variable number of tandem repeats (VNTR) region of a MUC2 cDNA clone. The MAbs reacted with synthetic MUC2 VNTR peptides but not synthetic MUC1 or MUC3 VNTR peptides, and showed specific reactivity in Western blotting with a high molecular weight protein produced by the LS174T colon carcinoma cell line. The use of shorter peptides indicated that the minimum peptide epitopes for these MAbs were different. Mab 3A2 reacted with amino acids 5-19 of the MUC2 VNTR by inhibition ELISA but not by direct ELISA, while 4F1 reacted with this peptide in both assays. Furthermore, 4F1 reacted in direct ELISA when a larger (29 amino acid) MUC2-derived peptide was coated onto the assay plate by incubating in carbonate buffer or by drying the peptide onto the assay plate, while 3A2 only reacted when this peptide was coated in carbonate buffer. The different specificity of the MAbs was also illustrated by the reactivity of 4F1 but not 3A2 with partially deglycosylated cystic fibrosis mucin. Immunohistochemical analysis with these MAbs revealed a strong reactivity with lung, gastric and colon tumours relative to normal tissue, with some breast and ovarian tumours also reacting. Both MAbs stained some normal goblet cells in the perinuclear region but not the mucin droplet or secreted mucin, indicating a reaction with immature (poorly glycosylated) mucin in the endoplasmic reticulum and/or golgi, but not with mature (fully glycosylated) mucin. In contrast, tumours showed strong diffuse cytoplasmic staining. 4F1 also showed weak apical cytoplasmic staining in some goblet cells and stained some tumours which showed no reactivity with 3A2. These antibodies should prove useful in the study of MUC2 structure and function, and in the diagnosis of some tumours.
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PMID:Monoclonal antibodies reacting with the MUC2 mucin core protein. 851 4


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