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

Tumour cell induced platelet aggregation (TCIPA) may facilitate haematogenous tumour metastasis. In this study of the aggregatory responses of human platelets to human tumour cell lines, we have found two distinct mechanisms of TCIPA. Colon carcinoma lines Colo 205 and Colo 397 produced TCIPA which was dependent upon thrombin generated through the activation of clotting factor VII, consistent with the expression of tissue factor activity by these cells. This mechanism was calcium dependent and was partially mediated by platelet ADP release as it was inhibited by apyrase. A uterine carcinosarcoma line (Colo 526) produced TCIPA by a novel mechanism which was dependent upon calcium, but was independent of thrombin generation and of the presence of plasma proteins, indicating that this aggregatory response is initiated by a direct platelet-tumour cell interaction.
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PMID:Plasma-dependent and -independent mechanisms of platelet aggregation induced by human tumour cell lines. 362 45

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

The concept that diet plays an important role in the initiation and/or development of various types of tumors in man and experimental animals is well documented. The etiology of colon cancer is complex and multifactorial in nature, and there is little information on the dietary components that may act as initiators during colon tumorigenesis. We have evaluated various dietary heterocyclic mutagenic amines present in a typical "Western" diet for their nuclear damaging effect (presumably a genotoxic response) on the colonic epithelium of C57BL/6J mice in vivo. Among the mutagenic amines studied 2-amino-3,4-dimethylimidazo(4,5-f)quinoline and 2-amino-3-methylimidazo(4,5-f)quinoline were very potent inducers of nuclear aberrations. These observations provide us with clues that our daily diet may contain colon-specific genotoxic components. Promotional effects of dietary fat and/or bile acids on colon tumorigenesis have been well studied. Dietary levels of calcium (0.1, 0.5 or 1.0% by weight) appear to modify the toxicity of orally administered fat or cholic acid (assessed by quantifying cell proliferation). The colons of animals consuming 0.1% or 0.5% calcium diet were more susceptible to the toxicity, whereas the colons of those consuming a 1.0% calcium diet appeared more like control colons. These studies demonstrate a profound effect of dietary constituents on the pathobiology of the colonic epithelium which may have a marked influence on the colon tumorigenesis.
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PMID:Effect of dietary components on the pathobiology of colonic epithelium: possible relationship with colon tumorigenesis. 371 47

Nine patients at high risk of developing colon cancer were placed on daily p.o. supplementation of 1500 mg of calcium for 4-8 weeks. The colonic epithelial cells in six of these patients showed a statistically significant decrease in their [3H]thymidine labeling indices in tissue culture so that they resembled those of patients at low risk of developing colon cancer. The three nonresponders had similar labeling indices before and after calcium supplementation. Biopsies from each of nine high-risk patients exhibited a decrease in proliferation when they were cultured in vitro with a high level of CaCl2 (2.2 mM compared with the 0.1 mM optimum value for proliferation). Two adenomas and two carcinomas showed a different pattern of response than normal cells, exhibiting no inhibition of growth at 2.2 mM CaCl2. These data indicate that the growth inhibition induced by high levels of extracellular calcium levels is lost at a stage in tumor development before cells become malignant.
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PMID:Inhibition of human colonic epithelial cell proliferation in vivo and in vitro by calcium. 375 91

There is increasing evidence that the enzyme protein kinase C (PKC) mediates the action of phorbol ester tumor promoters and also the action of certain growth factors. The present studies indicate that the bile acids chenodeoxycholate and deoxycholate inhibit the Ca2+-phosphatidylserine (PS)-dependent activity of PKC in the presence of 1 mM Ca2+, whereas seven structurally related bile acids do not detectably inhibit the enzyme under these conditions. Chenodeoxycholate and deoxycholate appear to inhibit PKC by interactions with both Ca2+ and PS, since their inhibitory potencies are reduced at an elevated PS concentration and since both of these bile acids actually enhance PKC activity, approximately 2-fold, when assayed at an elevated Ca2+ concentration (2 mM). Seven related bile acids also caused an approximately 2-fold enhancement of PKC activity in the presence of 2 mM Ca2+. Chenodeoxycholate and deoxycholate also caused an approximately 1.3-fold enhancement of PKC activity in the presence of 12-O-tetradecanoyl phorbol 13-acetate (TPA) and PS, and the absence of added Ca2+. Thus, depending on the reaction conditions, specific bile acids can act directly to inhibit or enhance PKC activity. There is evidence that during colon cancer formation, both in rodents and in humans, bile acids may act as tumor promoters. Thus the mediation of tumor promotion by bile acids in vivo may involve direct activation of PKC by the bile acids themselves. The present results suggest that the relative extents of absorption of Ca2+ and bile acids by the colonic mucosa may alter the activity of PKC in the mucosa, and thus alter the growth properties of this tissue. The present studies also suggest that lipophilic anionic compounds may provide a new approach to developing therapeutic agents that act by modulating PKC.
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PMID:The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several structurally related bile acids. 380 3

In a prospective cohort study, 8006 men of Japanese ancestry were examined from 1965 to 1968. A 24-h dietary recall questionnaire was administered to each subject as part of the baseline clinical examination. Dietary data were analyzed for intake of calcium, phosphorus, and total fat in 99 colon cancer cases and in 378 controls chosen from the cancer-free men. This was a nested case-control study design with 14-17 yr of prospective followup for colon cancer incidence. We found no significant association between dietary calcium intake and colon cancer risk. This held true whether phosphorus intake was low (less than 1032 mg/day) or high (greater than or equal to 1032 mg/day), and whether total fat intake was low (less than 61 g/day) or high (greater than or equal to 61 g/day). Adjusted-odds ratios were 0.7-1.4 across eight subgroups of low and high intakes of the three nutrients studied. These data do not support a recent hypothesis that calcium intake might be negatively associated with colon cancer risk, depending on the level of fat and phosphorus intake.
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PMID:Colon cancer and dietary fat, phosphorus, and calcium in Hawaiian-Japanese men. 394 95

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

Neoplasms affecting different subsections of the large bowel appear to have different risk factors. For the major type of neoplastic disease in the large bowel, that in the descending and sigmoid colon, a good association with nutrition and specific nutritional elements has been found. The risk of this type of colon cancer is proportional to the customary dietary fat intake--high in the Western World and low in the Orient. It is inversely proportional to stool bulk, which is itself modulated by cereal fibre intake. Fat and fibre, as the two major elements implicated, are sufficiently secure with regard to underlying scientific data and understanding of mechanisms, to permit utilising them to modify risk. Thus, a dietary regimen low in total fat, 20% of calories, and higher in cereal fibre, of the order of 30 grams/day, is indicated. Such a modified nutritional intake could be expected to reduce risk, not only in the general population, but most likely also in patients who have been treated successfully by conventional means. Additional evidence suggests that regular intake of yellow and green vegetables, of foods containing calcium salts, selenium and other micro-nutrients, lower the risk even more. More research is needed to provide the data necessary for deliberate intervention with these agents. Gastric cancer, on the other hand, has a distinct set of risk factors, namely, intake of pickled and salted fish or beans. Other risk factors are associated with residence in areas where the geochemical or agricultural sources of nitrate intake are not balanced by the presence of vitamin C, vitamin E, or certain phenolic antioxidants and nitrite traps such as pyrogallol, tannins, or peptides. The possible genotoxic carcinogen is not yet known, but it could be an alkyl-nitrosamide type of aryldiazonium chemical. The formation of such compounds is inhibited by vitamin C, vitamin E, and certain antioxidants. This fact can be used to decrease deliberately the risk of gastric cancer.
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PMID:Human and laboratory studies on the causes and prevention of gastrointestinal cancer. 609 59

Increased dietary fat was suggested to promote colon cancer by increasing the levels of free ionized fatty acids and bile acids in the colon contents. In the presence of calcium ions the irritating and toxic effects of the free acids on colon epithelial cells could be reduced by being converted to insoluble calcium soaps. The level of supplementary dietary calcium to supply adequate calcium and thus reduce the potential toxicity of dietary fat was considered.
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PMID:Colon cancer and dietary fat, phosphate, and calcium: a hypothesis. 658 52

A simple fluorescent microscopic method demonstrated that adriamycin was distributed in two cellular compartments of living rat colon cancer cells. Adriamycin accumulated slowly in cytoplasmic granules, probably lysosomes, where it persisted long after the drug was removed from the medium. On the other hand, adriamycin accumulated rapidly in the nucleus, but was rapidly cleared in adriamycin-free medium. Drug efflux from the nucleus was blocked by sodium azide in glucose-free medium or by verapamil, a calcium-blocking agent. When colon cancer cells were cultivated for 1 day or longer in adriamycin-containing medium no nuclear fluorescence was observed. However, the addition of sodium azide to glucose-free medium or verapamil restores the nuclear fluorescence. The colon cancer cells had low sensitivity to adriamycin, but the addition of verapamil strongly enhanced adriamycin toxicity. Thus adriamycin is permanently cleared from the nucleus of rat colon cancer cells through an energy-dependent efflux mechanism, which is blocked by verapamil. The efficiency of this efflux mechanism is enhanced by exposure of the cell to adriamycin. This mechanism could be involved in the resistance of colon cancer to adriamycin.
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PMID:Cytofluorescence localization of adriamycin in resistant colon cancer cells. 673 40


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