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

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.
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PMID:Hypergastrinemia in rats with azoxymethane-induced colon cancers. 770 52

Epidemiological studies have suggested that increased intake of calcium (Ca) or aspirin (ASA) is associated with a reduced risk for colon cancer. To delineate a possible mechanism of action, the present study used male F344 rats in an azoxymethane (AOM)-induced colon tumor model to study the single and interactive effects of Ca and ASA on cholic acid-promoted experimental colon carcinogenesis. Following initiation with AOM, a promotion diet containing 0.5% cholic acid was fed for 34 weeks until the adenoma development stage. Cholic acid was used as a surrogate for high-fat diets and to promote carcinogenesis. Diets were supplemented with CaCO3 (2% Ca by weight), 250 p.p.m. ASA, or both. After 34 weeks, the diets were switched during the progression stage and rats were killed at week 51. Several intermediate endpoints were examined during the course of AOM carcinogenesis to determine their reliability as predictors of colon cancer risk. Intermediate endpoints included colon crypt height measurement, colon mucosal ornithine decarboxylase (ODC) and colon mucosal protein kinase C (PKC) activities. The biomarkers were examined at the beginning of the study at 2 weeks, and thereafter at 5, 15, 30 and 40 weeks of dietary treatment. Animals were necropsied at week 51 and tumor incidence and numbers were analyzed for correlation with biomarkers. Survival was highest in the group fed CaCO3 during the promotion stage and tumor burden was lowest in groups fed CaCO3 during this stage. Supplementation during the progression stage was ineffective. The cholic acid promotion model resulted in increased ODC which was inhibited by intervention during the promotion stage with Ca, but not ASA. PKC was also activated by cholic acid feeding, and this effect was modulated by intervention in the promotional stage with Ca or ASA. Colon tumor incidence and burden was increased by cholic acid promotion and decreased by Ca, but not affected by ASA. In summary, Ca is a more effective chemopreventive agent in cholic acid-promoted colon carcinogenesis than ASA, impacting both incidence and tumor number. Colonic ODC, but not PKC may be a suitable predictor of risk and response in chemoprevention trials for colon cancer.
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PMID:Chemopreventive effects of calcium but not aspirin supplementation in cholic acid-promoted colon carcinogenesis: correlation with intermediate endpoints. 772 52

Clinical and experimental studies have shown that the carcinogenic process of colorectal mucosa is linked to the development of proliferative abnormalities which precede the occurrence of morphological abnormalities such as epithelial dysplasia. In humans, proliferative defects have been demonstrated in the normal rectal mucosa of population groups at risk for colon cancer. Several techniques are available to study cell kinetics in the gastrointestinal mucosa. Each explores different aspects of cell proliferation. We have attempted to evaluate the correlation between various techniques in the normal rectal mucosa of high-risk patients. We found a good correlation between bromodeoxyuridine (BrdU) labeling index and the mucosal activity of the enzyme ornithine decarboxylase, and between tritiated thymidine and the percentage of cells in the S phase of the proliferative cycle as determined by flow cytometry. However, these correlations concern only labeling indices, which can be influenced by physiological events, such as active inflammation or increased cell loss. It may not be the most reliable proliferative marker of cancer risk. Moreover, methods using cells isolated from homogenized tissue do not allow us to evaluate the pool of cells which are examined nor the distribution of proliferating cells within the tissue. For example, an inflamed mucosal specimen is highly infiltrated with inflammatory cells which can interfere with the measurement of epithelial cell proliferation. Nevertheless, the labeling index may be normal even in patients at high risk. For these reasons, we think that the most reliable methods are those using tissue culture, such as tritiated thymidine or BrdU uptake and proliferating cell nuclear antigen (PCNA) immunostaining.
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PMID:Methodological problems in the use of rectal cell proliferation as a biomarker of colorectal cancer risk. 782 6

Activity of ornithine decarboxylase (ODC), one of the rate-limiting enzymes in the pathway of polyamine biosynthesis, is regulated by various factors. In this study, we examined the role of Ca2+ in the regulation of ODC enzyme activity in mouse colon cancer cells (MC-26). KCl, a membrane-depolarizing agent that opens the voltage-dependent Ca(2+)-channel to increase intracellular Ca2+, decreased serum-induced ODC enzyme activity in MC-26 cells in a dose-dependent, reversible fashion. Both verapamil and nifedipine, inhibitors of the L-type voltage-dependent Ca(2+)-channel, decreased serum-induced ODC enzyme activity. W-7, a calmodulin inhibitor, decreased ODC enzyme activity in a dose-dependent, reversible fashion while trifluoperazine, another calmodulin inhibitor, failed to affect ODC enzyme activity in MC-26 cells. Our findings indicate that intracellular Ca2+ participates in the regulatory mechanism of ODC enzyme activity in MC-26 cells, although the exact role of Ca2+ is still unclear.
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PMID:Role of calcium in the regulation of ornithine decarboxylase enzyme activity in mouse colon cancer cells. 787 72

Modifying effects of dietary exposure of seven naturally occurring products on the development of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM) were investigated in male F344 rats. The effects of these compounds on proliferation biomarkers such as the number of silver-stained nucleolar organizer region protein, ornithine decarboxylase activity, and polyamine concentration in the colon were also estimated. The naturally occurring products tested included four terpenoids (rebaudioside A, oleanolic acid, costunolide, and soyasaponin A2), one flavonoid (liquiritin), and two isocoumarins (phyllodulcin and hydrangenol). Animals were given 3 weekly s.c. injections of AOM (15 mg/kg body weight) to induce ACF. These rats were fed the diet containing 200 ppm of each test chemical for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection to estimate their modulatory effects on the occurrence of ACF and the cell proliferation biomarkers in the colon. In groups of rats given AOM and hydrangenol, oleanolic acid, or costunolide, the frequencies of ACF/colon were significantly lower than that of AOM alone (P < 0.05, P < 0.005, and P < 0.05, respectively). In groups of rats given AOM and costunolide and those treated with AOM and soyasaponin A2, both ornithine decarboxylase activity and polyamine concentration of the colonic mucosal tissue were significantly decreased compared with those in rats given AOM alone (P < 0.05 and P < 0.001 for costunolide and P < 0.001 and P < 0.05 for soyasaponin A2, respectively). In groups of rats given AOM and liquiritin, oleanolic acid, or costunolide, the numbers of silver-stained nucleolar organizer regions/nucleus were significantly lower than that of AOM alone (P < 0.05, P < 0.01, and P < 0.05, respectively). Costunolide decreased four AOM-induced biomarkers, such as the frequencies of ACF/colon, ornithine decarboxylase activity, polyamine concentration level, and silver-stained nucleolar organizer region number in the colon. These results indicate that, among the test chemicals, costunolide has blocking effects against rat colon carcinogenesis and is a possible chemopreventive agent against colon tumorigenesis. Also, the short-term model described here could be a very useful prescreening tool for chemopreventive agents against colon cancer.
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PMID:Modifying effects of naturally occurring products on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats. 788 22

In our previous study, we demonstrated that azoxymethane (AOM) treatment significantly enhanced the expression of ras p21, the protein product of ras genes, and that the dietary administration of chemopreventive agents such as D,L-alpha-difluoromethylornithine (DFMO), a irreversible inhibitor of ornithine decarboxylase, and piroxicam, a non-steroidal anti-inflammatory drug (NSAID), exerted a significant inhibitory effect on AOM-induced ras p21 expression. In the present study, which is an extension of our earlier investigation, we have determined the effect of DFMO and piroxicam on mutational activation of ras protooncogenes during AOM-induced colon carcinogenesis. Groups of male F344 rats were fed the modified AIN-76A diet containing 0 or 150 p.p.m. piroxicam, or 4000 p.p.m. DFMO and administered s.c. AOM dissolved in normal saline at a dose rate of 15 mg/kg body wt, once weekly, for 4 weeks. Vehicle control groups received s.c. equal volumes of normal saline. Groups of animals were then killed at 0, 4, 16, 24 or 32 weeks after last AOM or saline injection. AOM-induced colon tumors and colonic mucosa from AOM treated as well as saline treated animals were analyzed for point mutations in K- and H-ras protooncogenes by a combination of polymerase chain reaction mediated restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Our results demonstrate that of the total 65 AOM-induced colon tumors analyzed, 45/50 (90%) obtained from AOM-treated animals fed the control diet, 4/11 (36%) from AOM-treated animals fed piroxicam diet, and 1/4 (25%) from AOM-treated animals fed the DFMO diet, contained single-point mutations occurring specifically at the second nucleotide of codon 12 which were identified exclusively as G to A transitions in case of K-ras, and G to A transitions and also G to T transversions in H-ras. Similar point mutations were identified in colonic mucosa of 21/30 (70%) of AOM-treated animals fed the control diet, 10/30 (33%) of AOM-treated animals fed piroxicam diet, and none of 30 (0%) of AOM-treated animals fed DFMO diet. These results indicate that the administration of piroxicam and DFMO may inhibit the selective amplification of AOM-induced initiated cells carrying mutated ras genes. Dietary DFMO exerted more pronounced inhibition of selective amplification of initiated cells containing AOM-induced mutant ras. Data suggest that determination of ras activation may be a useful marker for chemoprevention of colon cancer.
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PMID:Modulation of azoxymethane-induced mutational activation of ras protooncogenes by chemopreventive agents in colon carcinogenesis. 803 6

Reflux esophagitis is a common disease in infants and can be diagnosed largely by esophageal biopsy. In adults, chronic esophagitis may lead to Barrett's esophagus, a premalignant condition for esophageal cancer development. Ornithine decarboxylase (ODC) is used as an early marker for colon cancer development. No data are available on the role of ODC in reflux esophagitis in the pediatric population. In this study we retrospectively analyzed ODC activity in esophageal biopsies of children who underwent upper endoscopy. According to the esophageal histology, patients were divided into three groups: normal mucosa, mild, and moderate/severe esophagitis. None of our patients had esophageal metaplasia or cancer. ODC level was significantly higher in the moderate/severe esophagitis group compared to mild and normal mucosa group. We conclude that ODC activity is directly proportional to the severity of the esophageal inflammation/regenerative process in children with reflux esophagitis.
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PMID:Ornithine decarboxylase (ODC) levels in children with reflux esophagitis. 814 36

Selenium metabolism and polyamine biosynthesis are linked in their common requirement for S-adenosylmethionine. The effects of selenium supplementation (0.1 to 6.0 ppm) on growth, polyamine biosynthesis and S-adenosylmethionine were examined in two human colon cancer cell lines, WiDr and HT29. WiDr cells were very sensitive to selenium with a significant decrease in 3H-thymidine incorporation and cell number to doses above 0.25 ppm. HT29 cells were less sensitive. In HT29 cells, ornithine decarboxylase activity and its product putrescine decreased in parallel with the growth inhibitory effects of selenium. Similar changes were not noted in WiDr cells. Spermidine and spermine content were conserved in both cell lines exposed to cytotoxic doses of selenium. S-adenosylmethionine was increased in HT29 cells at cytotoxic doses of selenium (1.0 to 6.0 ppm).
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PMID:Effect of selenium on growth, S-adenosylmethionine and polyamine biosynthesis in human colon cancer cells. 831 17

Colonic adenocarcinoma affects approximately 6% of adults in many Western countries. beta-Carotene (BC), a safe, inexpensive, and widely available compound, has been proposed as a cancer chemopreventive agent. To evaluate whether BC shows promise as an inhibitor of colonic carcinogenesis, we studied 20 male subjects who had previously undergone resection of colonic adenocarcinoma. Each subject received beta-carotene, 30 mg orally, daily for 6 months. Rectal mucosa was sampled at multiple intervals prior to, during, and following BC administration. Mucosal ornithine decarboxylase (ODC) activity and serum and mucosal BC concentrations were determined at each interval. ODC activity was inhibited by 44% (P < 0.05) and 57% (P < 0.01) after 2 and 9 weeks, respectively, of BC administration and remained low compared with baseline even 6 months following discontinuation of BC. Serum and mucosal BC concentrations increased as expected during BC administration and remained elevated for 6 months following BC discontinuation. The demonstrated inhibition of rectal mucosal ODC activity in these patients with resected colon cancer suggests that BC may prove useful as a cancer chemopreventive agent.
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PMID:beta-Carotene inhibits rectal mucosal ornithine decarboxylase activity in colon cancer patients. 833 82

Our previous study has shown that dietary administration of protocatechuic acid (PCA) acts as potential chemopreventive agent in inhibiting diethylnitrosamine-induced liver carcinogenesis in male F344 rats. The present study was designed to determine the modifying effect of PCA on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats and the effect on intermediate biomarkers, i.e., colonic mucosal ornithine decarboxylase activity and colonic epithelial proliferation, which can be used as effective predictors of colon cancer. Staring at 6 weeks of age, groups of animals were fed the basal diet and experimental diet containing PCA at dose levels of 250, 500, and 1000 ppm. At 7 weeks of age, all animals except the PCA alone group (1000 ppm) and untreated controls were given s.c. injections of AOM at a dose level of 15 mg/kg body weight/week for 3 weeks. PCA at 3 doses was fed during the initiation phase (before 1 week, during, and after 1 week of AOM exposure) or postinitiation phase (for 28 weeks starting 1 week after the last injection of AOM). All animals were then killed at 32 weeks after the start and colonic tumor incidence and multiplicity were determined. Animals intended for cell proliferation study were given injections of bromodeoxyuridine/5-fluoro-2'-deoxyuridine (1 ml/100 g body weight) 1 h prior to be killing. The rate of colonic cell proliferation in the distal portion was assessed by immunohistochemistry using antibromodeoxyuridine and by counting silver-stained nucleolar organizer regions protein. The colonic mucosal ornithine decarboxylase activity was also measured at the termination. The results indicate that dietary PCA administration at 500 and 1000 ppm during the initiation or postinitiation phase significantly inhibited intestinal carcinogenesis induced by AOM as revealed by the reduction of tumor incidence and multiplicity. The data also demonstrate that PCA at 500 ppm and 1000 ppm significantly inhibited bromodeoxyuridine labeling index and also silver-stained nucleolar organizer regions protein number at three doses when animals were fed PCA at the initiation or postinitiation stage. Also, feeding of PCA at 1000 ppm during the initiation and postinitiation phase exerted a pronounced inhibitory effect on the colonic ornithine decarboxylase levels. PCA feeding did not cause any toxicity. These results demonstrate that PCA is a possible new chemopreventive agent for colon carcinogenesis through the suppression of manifestation of intermediate biomarkers induced by AOM, although the precise mechanisms of PCA-induced inhibition during the initiation and postinitiation phases remain to be elucidated.
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PMID:Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid: suppressing effects on tumor development and biomarkers expression of colon tumorigenesis. 835 16


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