Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal healthy volunteers (n = 8) received low- and high-fat (14% and 53% energy/day, respectively) and dietary fiber-supplemented high-fat diets (fiber 25 g/day, fat 52% energy/day) for 10 days each. Colon cancer risk factors in feces were measured by colonic nuclear aberration assay, the Ames Salmonella test using strain TA100, and measurement of bile acids and calcium soaps. Nuclear aberrations in colonic epithelium increased during the high-fat diet period and then decreased during the fiber-supplemented high-fat diet period. There were no significant differences in the mutagenicity on Salmonella TA100 or in the concentration of bile acids during the high-fat diet period. Bile acids decreased during the fiber supplementation period. The marked increase in calcium soaps during the high-fat diet period indicates an increase in long-chain fatty acids in the fecal lipid component and conversion of these fatty acids to insoluble calcium soaps when enough calcium is present.
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PMID:Effect of low-fat, high-fat, and fiber-supplemented high-fat diets on colon cancer risk factors in feces of healthy subjects. 132 40

Like calcium, vitamin D may protect against colorectal neoplasia as it reduces epithelial cell proliferation and induces differentiation. Although its therapeutic use is limited by its effects on calcium metabolism, analogues such as calcipotriol produce little hypercalcaemia. Stathmokinetic and immunohistochemical techniques were used to study the effect of 1,25 (OH)2 D3 and its analogues on cell proliferation in human rectal mucosa and a colon cancer cell line. Paired sigmoidoscopic biopsy specimens were obtained from 17 control patients and five patients with familial adenomatous polyposis. Explants were established in organ culture, with or without the addition of vitamin D. Proliferation was assessed using (1) metaphase arrest to determine the crypt cell production rate (CCPR) and (2) Ki-67 monoclonal antibody directed against an antigen present in proliferating cells. 1,25 (OH)2 D3 in concentrations of 1 microM-100 pM (10(-6)-10(-10) M) reduced the CCPR (cells/crypt/hour) from 4.74 to 2.15-2.67 (p < 0.001), and the Ki-67 labelling index from 7.28-3.74 (p < 0.01). Likewise, vitamin D2, 10 nM (10(-8) M) reduced the CCPR from 4.74-2.74 (p < 0.05) and calcipotriol from 4.86-2.38 (p < 0.05). In familial adenomatous polyposis patients 1,25 (OH)2 D3 100 pM (10(-10) M) halved the CCPR from 8.75-4.22. Calcipotriol (10(-5) M to 10(-9) M) produced a clearcut dose response inhibition of HT-29 cell growth. Thus, vitamin D and its metabolites inhibit proliferation in normal and premalignant rectal epithelium and suppress growth in a colorectal cancer cell line.
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PMID:Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line. 133 58

Lactobacilli belong to the normal oropharyngeal and intestinal microflora in humans. These microorganisms contribute to the stabilization of the microflora and maintain the colonization resistance against pathogens. Lactobacilli have been used as dietary supplements in order to prevent gastrointestinal disturbances. Claims have been made that certain strains of lactobacilli possibly exert anticarcinogenic activities. The activity of bacterial enzymes, implicated in colon carcinogenesis may be elevated by a high meat, Western-type diet. Supplements of Lactobacillus acidophilus decreased these levels in both rats and humans. Colon cancer patients given L. acidophilus fermented milk showed a significant increase both in numbers of intestinal lactobacilli and dietary calcium intake, while decreasing trends in levels of both soluble faecal bile acids and faecal bacterial enzymes, two risk makers for colon cancer, were observed. In vitro studies have revealed that lactobacilli and other lactic acid bacteria have the ability to absorb cooked food mutagens. Recent studies in humans have shown that intake of L. acidophilus significantly reduced the mutagen excretion after consumption of fried meat. Several mechanisms by which lactobacilli might exert anticarcinogenic effects are discussed. Thus, certain strains of lactobacilli might lower the colon cancer risk in humans.
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PMID:Lactobacilli, anticarcinogenic activities and human intestinal microflora. 146 86

The diets of 746 colon cancer cases in Los Angeles County, California (USA) were compared with those of 746 controls matched on age, sex, race, and neighborhood. In both genders, total energy intake was associated with significantly increased risk, and calcium intake was associated with significantly decreased risk. These effects were reduced only slightly after adjustment for the nondietary risk factors (weight, physical activity, family history, and, if female, pregnancy history). In men, total fat and alcohol intakes were responsible for the calorie effect; in women, no individual source of calories was associated independently with risk. Neither saturated fat nor fat from animal sources was responsible for the fat effect. There were no additional independent significant effects for sucrose, fiber, cruciferous vegetables, beta-carotene, other vitamins, or any other nutrient or micronutrient. In univariate analyses, meats, poultry, breads, and sweets were associated with excess risk, and yogurt was protective. After adjustment for sources of calories, no individual food was associated with excess risk, but yogurt remained significantly protective. Total calories were associated with excess risk throughout the colon while the effects of calcium, fat, and alcohol appeared somewhat stronger in the distal colon. After adjustment, crude fiber was significantly protective in the ascending colon but not even weakly protective in the distal colon.
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PMID:Diet and colon cancer in Los Angeles County, California. 152 27

Fecapentaenes are strong fecal mutagenic compounds presumably occurring in the majority of Western human individuals, and are possibly essential initiators of colon carcinogenesis. Dietary factors have been shown to influence colorectal cancer risk and to modulate both fecal mutagenicity and fecapentaene concentrations. Therefore, in this study, excretion of fecapentaenes is determined in humans consuming either vegetarian or omnivorous diets. The results show that the most predominant fecapentaene forms are excreted in higher concentrations by vegetarians. Consumption of cereal fiber, calcium and carotene as well as fecal concentrations of iso-lithocholic acid were found to correlate positively with excreted concentrations of one or more fecapentaene analogues. On average, 22% of excreted fecapentaene concentrations was found to be related to nutrient intake in stepwise regression models. Dietary calcium intake was found to be the most significant factor positively correlating with excreted fecapentaene concentrations. Intake of mono-unsaturated fatty acids or fiber from vegetables and fruit could be shown to correlate with fecapentaene excretion to a lesser degree. Despite high fecapentaene concentrations in fecal dichloromethane extracts, only 1 out of 20 samples revealed significant mutagenic activity in Salmonella typhimurium TA 100. Further, aqueous extracts of feces from omnivores appeared to be equally mutagenic as feces from vegetarians and contained non-detectable concentrations of fecapentaenes. It is concluded that dietary factors do affect excreted fecapentaene levels, but only to a relatively minor extent. Since vegetarians at low risk for colorectal cancer excrete higher concentrations of fecapentaenes, it could be hypothesized that relatively increased fecapentaene excretion in combination with antimutagenic compounds in feces represents colon cancer prevention.
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PMID:Fecapentaene excretion and fecal mutagenicity in relation to nutrient intake and fecal parameters in humans on omnivorous and vegetarian diets. 154 Sep 28

Nutrition has always been a subject of great interest to athletes. In recent years use of exercise has, however, expanded from competitive sports to prevention/management of chronic diseases and maintenance of optimal health. Exercise is recommended in the prevention/management of noninsulin-dependent diabetes, hypertension, coronary heart disease, osteoporosis, obesity, mental health, colon cancer, stroke and back injury. Similarly, there is evidence that certain nutrients (e.g., vitamins C and E, beta-carotene and calcium) may reduce the risk of certain cancers, coronary heart disease, osteoporosis, hypertension and cataract. Thus, there seems to be concordance between the health benefits of exercise and certain nutrients. However, several human and animal studies suggest that strenuous exercise may promote free radical production, leading to lipid peroxidation and tissue damage. On the other hand, there is evidence that vitamins C and E and beta-carotene may protect against such damage. Thus, concordance between the health benefits of exercise and nutrition and a compensatory role of antioxidant nutrients against the potentially harmful effects of exercise suggests that nutrition and exercise should form important components of any regimen for prevention of chronic diseases and/or promotion of optimal health.
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PMID:A current perspective on nutrition and exercise. 154 45

Calcium contributes to the progression of epithelial cells through all phases of the proliferative cycle and into stages of cell differentiation; intracellular concentrations of calcium that are required for cell renewal, however, are lower than those required for epithelial-cell differentiation. These effects of calcium are modulated by interactions with 1,25-dihydroxy-vitamin D3, phosphate, and fatty acids, all of which are partly dependent on dietary intake. In rodent models, increased dietary calcium inhibited hyperproliferation of colon epithelial cells induced by increased levels of fatty acids or bile acids present in the colon. When carcinogens induced hyperproliferation of colon epithelial cells the hyperproliferation was decreased by added dietary calcium, and in several animal models the occurrence of carcinogen-induced carcinomas of the colon decreased with increased dietary calcium. A nutritional stress diet, designed to represent human Western dietary intake of calcium, phosphate, vitamin D, and fat, produced hyperproliferation and hyperplasia in the colons of rodents; these effects were reduced by increasing dietary levels of calcium. Decreased levels of ornithine decarboxylase also were reported in human and rodent colon mucosa exposed to increasing levels of calcium. In human subjects at increased risk for familial colon cancer, hyperproliferation of colon epithelial cells was reduced after oral dietary supplementation with calcium. In epidemiological studies, several investigators reported inverse correlations between levels of dietary calcium intake and the incidence of colon cancer. Extrapolation of the data have suggested a protective effect of total calcium intakes above 1500 to 1800 mg/day.
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PMID:Calcium, vitamin D, and colon cancer. 154 42

Aberrant signal transduction has been implicated in malignant transformation, growth, and progression. This has led to the proposal to use inhibitors of signal transduction pathways to treat cancer. One approach to circumventing potential toxicity and improving efficacy would be to target pathways upon which cancer cells selectively depend. Pathways associated with the malignant process involve calcium fluxes, the release of arachidonic acid, and the generation of phosphoinositides. In this report, CAI (L651582, NSC 609974), a substituted carboxyamido-imidazole and novel inhibitor of these selected signal transduction pathways, inhibits anchorage-dependent and -independent growth in a large series of human cancer cell lines. CAI pretreatment of HT-29 human colon cancer and 5R ras-transfected rat embryo fibroblast cells inhibits the formation and growth of experimental pulmonary metastases in nude mice. Oral administration of CAI in PEG-400 vehicle arrests growth and metastasis of transplanted human melanoma and ovarian cancer xenografts. No significant gross or histological toxicity was observed at CAI doses yielding blood levels in the concentration range demonstrated to inhibit select signal transduction pathways in vitro. These data indicate the feasibility and demonstrate a potential selectivity and sensitivity of using specific signal transduction inhibitors for the experimental treatment of cancer.
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PMID:In vivo efficacy of a novel inhibitor of selected signal transduction pathways including calcium, arachidonate, and inositol phosphates. 159 30

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

The influences of different calcium concentrations in the culture medium on in vitro growth kinetics (generation time and saturation density) of established human colonic mucosal lines derived from subjects with and without familial adenomatosis of the colon and rectum were studied to test the hypothesis that hyperproliferation of colonic mucosal cells observed in some familial colon cancer can be reversed by increased extracellular calcium concentration. From the present studies, the genomic source of the adenomatous colonic lines appear to modify the effect of increased calcium on mucosal growth as demonstrated by differences in growth response in lines with and without the biomarker associated with genetic predisposition for some colon cancers, increased in vitro tetraploidy. Such observations suggested that other factors, including genomic differences, should be taken into consideration in the determination of the possible influences of calcium concentration on colonic mucosal proliferation.
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PMID:Effect of increased calcium concentration on in vitro growth of human colonic mucosal lines. 164 91


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