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

Interferon (IFN) increases cytoplasmic free calcium ([Ca2+]i) in RPMI 4788 cells, a human colon cancer cell line. Addition of IFN to the cells loaded with Fura-2, a fluorescent Ca2+ indicator, causes an immediate increase in [Ca2+]i, which is the earliest event after IFN stimulation. A cyanine dye, dis-C3- (5) was used to determine the effects of IFN on the membrane potential in cancer cells. The depolarization was seen with IFN-gamma, but not with IFN-beta. These results taken together, suggest that the IFN-gamma and -beta induced [Ca2+]i mobilization are clearly different in their dependence on Ca2+ entry through voltage-gated Ca2+ channels.
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PMID:Interferon-gamma activates the voltage-gated calcium channel in RPMI 4788 cells. 245 15

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

Supplemental dietary calcium decreased and normalized hyperproliferation of colonic epithelial cells in individuals in familial colon cancer kindreds, measured by rates and patterns of [3H]thymidine labeling of epithelial cells in colonic crypts. In whole colonic crypts hyperproliferation was decreased to lower levels in over one-half of the subjects individually studied during the course of the calcium supplementation regimen. The remaining familial colon cancer subjects did not show reductions in cell proliferation measured over the whole crypt. However, when their cell-labeling data were analyzed in regions of the colonic crypt, the size of the proliferative compartment decreased and contracted towards the crypt base after calcium, a pattern typical of individuals at decreased risk for colonic cancer. This contraction of the proliferative region of the crypts occurred through decreased cell labeling in the two crypt compartments closest to the luminal surface and increased cell labeling in the second crypt compartment nearest to the base of the crypt. Following in vitro exposure of colonic epithelial cells to increasing physiological amounts of calcium, cell proliferation in familial colon cancer subjects decreased uniformly and greater heterogeneity in responsiveness was observed in cells from individuals with familial polyposis.
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PMID:Colonic epithelial cell proliferation in responders and nonresponders to supplemental dietary calcium. 253 92

Epidemiologic studies of the relationship of diet to cancer etiology are hampered by methodologic difficulties which can be overcome by careful trial design. The use of appropriate dietary assessment instruments is necessary to minimize bias and improve accuracy of diet assessment. Population studies implicate dietary fat intake in the etiology of colorectal carcinogenesis, and the incidence of colorectal malignancies around the world is positively correlated with meat and fat consumption and total calorie intake. Retrospective studies of fat intake yield equivocal results, whereas prospective studies have failed to show a relationship between fat intake and colon cancer risk. An inverse relationship exists between fiber consumption and colorectal cancer incidence and mortality rates. The positive observational studies are supported by laboratory studies of experimental carcinogenesis which show a greater number of tumors in animals fed high-fat or high-calorie diets. Increased fiber intake appears to offer some protection against colorectal cancer. Plausible mechanisms have been proposed in animals for the role of fat and fiber in colorectal carcinogenesis; the mechanisms in human populations await further description. The interrelationships between fat consumption and consumption of dietary fiber and micronutrients have made it difficult to assess the roles of these substances in the etiology of colorectal cancer. Calcium offers protection in animal systems, and the data in humans are suggestive but not yet conclusive. Data on the role of alcohol in colorectal carcinogenesis remain inconclusive. Little evidence exists for a protective effect of retinoids and carotenoids; the evidence for selenium and vitamin C is limited and evolving.
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PMID:Dietary epidemiology of colon cancer. 253 85

A biomarker of increased risk for colon cancer is abnormally high proliferation of colonic epithelial cells. The authors developed an in vitro assay that measures the ability of human colonic epithelial cells that are in progressive stages of abnormal development to respond to direct application of calcium as the chloride in tissue culture medium. Incorporation of 3H-thymidine and autoradiography in situ was employed to measure the number of proliferating cells cultured at 0.1 mM CaCl2, the optimum level for growth, and 2.2 to 5 mM, both levels achievable in the colonic lumen. Abnormal cell proliferation was reduced in biopsies from 13 of 14 patients without familial polyposis but at increased risk for colon cancer because of previous colonic neoplasms or familial association; in cells from three of four asymptomatic individuals in familial polyposis families at risk for that disease; and in cells of three of ten patients symptomatic with familial polyposis. Growth of tubular adenoma cells from two of seven familial polyposis patients was also inhibited by calcium. Growth inhibition was not observed in more advanced colon tumors including eight adenomas, either villotubular or villous, and five carcinomas. These findings indicate heterogeneity within the familial polyposis phenotype for the normal cellular response to growth inhibition by calcium, and a further loss of response to calcium as these cells progress toward malignancy.
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PMID:Heterogeneity in the response of familial polyposis epithelial cells and adenomas to increasing levels of calcium in vitro. 254 88

Animal tumor experiments and epidemiologic studies suggest that several agents may be of potential value in blocking the development of colon adenomas and carcinoma. Recent laboratory investigations have demonstrated several intermediate markers that are altered in the colonic epithelium of high-risk individuals and that can be modulated by several possible chemopreventive agents. Calcium and ascorbic acid are two agents that have been investigated in preliminary studies. Although the results have not been striking, these studies have pointed up methodologic issues that must be addressed and will contribute greatly to the design of the next generation of trials. Given the advances in the elucidation of the carcinogenic processes in colon cancer, it is reasonable to hope that the next decade of research will discover chemoprevention strategies that will protect individuals from the development of the most common tumor in Western society.
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PMID:Chemoprevention of colon cancer. 264 72

This paper provides an overview of our knowledge on the involvement in cancer of vitamins A, C and E and of calcium, selenium and zinc. This work is a background for studies on dietary magnesium's effects on cancer. Consumption of vitamin A and its dietary precursors has been associated with reduced cancer at several sites in human and animal studies. Carcinogenesis studies using several models of cancer have been conducted on the influence of vitamin A deficiency, vitamin A excess and supplementation of vitamin A analogues. Vitamins C and E are effective in the prevention of N-nitroso compound (nitrosamine) formation. Vitamin C is effective in aqueous and vitamin E is effective in non-aqueous media. Both of these vitamins also have inhibited carcinogenesis by preformed carcinogens at several sites, but enhancement has been observed at some sites when excess vitamin treatment was studied. The potential role of calcium in the prevention of colon cancer is being pursed. Few experimental studies have been conducted but data support an effect of calcium on colonic epithelial proliferation. Epidemiological and especially experimental results suggest an inhibition of cancer by dietary selenium. In animal studies, selenium supplementation has been particularly effective in inhibiting colon and mammary carcinogenesis, but enhanced carcinogenesis was observed in some studies on skin, liver and pancreas cancer. Data suggest that zinc deficiency may be a factor in esophageal cancer; however, studies on tumor growth have demonstrated retarded tumor growth in zinc-deficient animals.
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PMID:Effects of the intake of selected vitamins and minerals on cancer prevention. 266 27

Long-standing investigations into the role of diet in colon cancer have generally supported the notion that some aspect of dietary fats acts to promote cancer at this site. Understanding of the chemical behavior of lipids in the colon led to a hypothesis suggesting that depletion of calcium could partly explain the tumor-promoting effects of dietary fat. Calcium levels may control critical intracellular events in the course of proliferation. Lack of availability or loss of calcium may result in abnormalities in the regulation of colonic proliferation. Basic and clinical studies suggest that calcium supplementation reduces colonic proliferation implying a potential reduction in cancer risk. The current evidence supporting calcium as a cancer chemoprevention agent is reviewed.
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PMID:Basic and clinical investigations of dietary calcium in the prevention of colorectal cancer. 269 61

Recent findings suggest that supplemental calcium could lower the abnormally high proliferation rate found in the colonic mucosa of subjects at high risk for colon cancer. In this double blind controlled study, this effect in volunteers previously operated upon for a colorectal adenocarcinoma was tested. Thirty subjects were randomised to receive either elemental calcium 1200 mg/day or a placebo. Mucosal proliferation was measured with tritiated thymidine labelling before and after the 30 day intervention period. Diets, faecal pH and the concentration of calcium and bile acids in the aqueous phase of feaces were also measured. Labelling index did not differ significantly in the two groups before intervention (placebo 4.0(2.4) v calcium 4.9(2.9), but the difference approached significance afterwards (4.4(2.4) v 6.5(3.4), p = 0.06). Individual changes occurring with intervention were tabulated and comparison of the means for the groups was not significant (delta = 0.3 vs delta = 1.8, p = 0.11). Calcium concentration, faecal pH and deoxycholic acid concentration increased in the calcium group (p = 0.02, 0.005 and 0.004 respectively). Calcium does not show any effect in decreasing colonic mucosal proliferation in this high risk group for colon cancer; it may increase faecal pH and the production of deoxycholic acid in the colon.
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PMID:Effect of calcium supplementation on mucosal cell proliferation in high risk patients for colon cancer. 270 38

Dietary calcium may inhibit colonic carcinogenesis promoted by high fat, phosphate, and low fibre diets. In persons at risk for colon cancer oral calcium supplements significantly suppress increased rectal epithelial proliferation. This was studied in a cohort of 35 volunteers: 26 first degree relatives of colorectal cancer patients and nine who had had colonic adenomas (mean age 51.6 years, 17 (49%) men, all negative for large bowel neoplasia). 1.25-1.5 g elemental calcium was given in divided daily doses for three months. Rectal pinch biopsies were taken without bowel preparation, before and mean 8.4 weeks during and 7.2 weeks after treatment and incubated with tritiated thymidine. The mean number of labelled cells, as a ratio of the total number of crypt cells (labelling index-LI), and their crypt position, were determined. The mean number of labelled cells decreased during treatment by 29%, especially in the basal three-fifths of crypts. There was also a significant 10% increase in mean number of crypt cells during treatment. [Mean LI decreased by 36% (p less than 0.001) during calcium treatment and almost returned to basal values after cessation.] If a raised LI is a marker of potential malignancy and a randomised clinical trial confirms that calcium suppresses it, dietary intervention studies in high risk persons are indicated.
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PMID:Oral calcium suppresses increased rectal epithelial proliferation of persons at risk of colorectal cancer. 273 58


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