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

Epidemiological and experimental studies indicate a strong association between an elevated colon cancer risk and increased fecal excretion of secondary bile acids, neutral sterols, and prolonged gastrointestinal transit time. Starch malabsorption, on the other hand, has been reported to be a possible protective factor in colon carcinogenesis. To study the impact of starch malabsorption on these parameters, 12 healthy volunteers consumed a diet rich in starch for two 4-week periods. During a double-blind crossover trial they received the alpha-glucosidase inhibitor acarbose (BAY g 5421) in one of the study periods and placebo in the other. During acarbose treatment stool wet weight increased by 68%, stool dry weight by 57%, and gastrointestinal mean transit time by 30%. Fecal concentrations (mg/g dry weight) of the neutral sterols coprostanol, coprostanone, campesterol, 4-cholesten-3-one, and beta-sitosterol decreased by 36.8, 48.7, 42.1, 34.6, and 39.4%, respectively, under acarbose. Concentrations of the major secondary bile acids, deoxycholic and lithocholic acid, decreased by 59.9 and 52.2%, respectively. In spite of an increased stool weight, also daily excretion (mg/day) of these two bile acids was lower under acarbose (47.9 and 36.6%, respectively) compared to placebo, whereas excretion of the main primary bile acid, cholic acid, rose from 22.58 mg/day to 379.80 mg/day during the acarbose period. The changes in fecal bile acid and neutral sterol excretion found during acarbose treatment may explain a protective effect of starch malabsorption on colon cancer development.
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PMID:Effect of starch malabsorption on fecal bile acids and neutral sterols in humans: possible implications for colonic carcinogenesis. 186 44

The growth of three non-tumorigenic human colonic adenoma cell lines, designated AA/C1, RG/C2 and RR/C1, was inhibited by low concentrations of transforming growth factor beta (TGF-beta) (0.05-0.5 ng ml-1). However, the growth of five human colon cancer cell lines under identical conditions was resistant to high concentrations of TGF-beta (2-10 ng ml-1). This is the first report of well-characterized premalignant human colonic cells showing sensitivity to TGF-beta. The TGF-beta-sensitive adenoma cell line AA/C1 was derived from a relatively large adenoma with a K-ras gene mutation and represents a relatively late-stage adenoma, indicating that loss of response to TGF-beta occurs at a relatively late stage in colorectal carcinogenesis and that the presence of a ras gene mutation does not necessarily confer resistance to TGF-beta. Of further interest, the RG/CZ cell line has a p53 mutation showing that p53 mutations do not necessarily lead to TGF-B insensitivity. Furthermore, in this paper we show that the conversion of the AA/C1 adenoma cell line to a tumorigenic phenotype [Williams et al., (1990) Cancer Res., 50, 4724] is accompanied by a reduced response to the growth-inhibitory effects of TGF-beta up to 10 ng ml-1. Reduced responsiveness to the inhibitory effects of TGF-beta may be an important event in the loss of growth control in colorectal carcinogenesis.
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PMID:Differential sensitivity of human colonic adenoma and carcinoma cells to transforming growth factor beta (TGF-beta): conversion of an adenoma cell line to a tumorigenic phenotype is accompanied by a reduced response to the inhibitory effects of TGF-beta. 188 18

Experimental evidence suggests that folate depletion plays a role in carcinogenesis. A case-control study examining folate intake was conducted. Some 428 colon and 372 rectal cancer cases with matched neighbourhood controls were interviewed regarding usual intake of foods, including food preparation. Unadjusted folate was not associated with risk of either cancer. Controlling for kilocalories, odds ratios (ORs) for those with the highest folate intake were 0.5 (95% confidence interval (CI): 0.24-1.03) and 0.31 (95% CI: 0.16-0.59) for females and males for rectal cancer. There was no change in colon cancer risk associated with folate intake. There was an indication of an interaction of folate and alcohol intake; the difference in risk associated with low and high folate intake was highest for males in the highest alcohol category. Associations were of similar magnitude for other dietary factors correlated with folate. It appears that intake of folate or a correlated factor may be negatively related to risk of rectal cancer.
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PMID:Folate intake and carcinogenesis of the colon and rectum. 191 36

Seven-week-old Sprague-Dawley rats were fed a semipurified AIN76 diet and were given a weekly injection of the colon carcinogen 1,2-dimethylhydrazine for 8 weeks (initiation stage of carcinogenesis). The rats were divided into seven groups and each group of rats was placed on one of seven different modifications of the AIN76 diet for the next 24 weeks (promotional stage of carcinogenesis). The mean numbers of aberrant crypt foci/rat and the incidence of adenocarcinomas from some of the seven dietary groups were found to be significantly different. However, all attempts to show a significant correlation between the mean number of aberrant crypt foci/rat and the incidence of adenocarcinomas failed. Therefore, the number of aberrant crypt foci/rat cannot by itself be used as a reliable quantitative predictor (biomarker) of the efficacy of dietary intervention or of chemopreventive procedures on modulating the risk of developing colon cancer. This conclusion emphasizes the need for end point validation of potential cancer biomarkers before the biomarkers can be considered predictive of modulation of the risk for colon cancer.
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PMID:Demonstration of the need for end point validation of putative biomarkers: failure of aberrant crypt foci to predict colon cancer incidence. 193 3

Foci of aberrant crypts (ACF) have been identified in the unsectioned methylene blue stained rodent colons and hypothesized to represent precursor lesions of colon cancer. In the present study, induction and growth characteristics of ACF were investigated in response to a single injection of varying dosages of 1,2-dimethylhydrazine-2HCl (DMH), a colon carcinogen. Female Sprague-Dawley rats were given a single injection of DMH (5-150 mg/kg). Two and 19 weeks after the injection, animals were killed and their distal 10 cm of colons were enumerated for the number and crypt multiplicity of ACF. Number of ACF increased with increasing dosages of DMH plateauing at 100 mg/kg. However, percentage of ACF exhibiting different crypt multiplicity (1 to greater than 4) were similar among different dose groups. Aberrant crypts and normal crypts were enumerated for total number of cells and number and distribution of S-phase cells along the crypt height 19 weeks after DMH injection after autoradiography. The labeling index (LI) (percentage of S-phase cells) and LI along the crypt height were determined. Compared to the surrounding normal crypts, aberrant crypts exhibited significantly higher (P less than 0.05) number of cells (1122 +/- 81 versus 411 +/- 28) and higher (P less than 0.05) LI (21 +/- 1 versus 12 +/- 1). For the eight ACF analysed in the present study, the distribution of S-phase cells in the aberrant crypts were similar to that of normal crypts in that S-phase cells were restricted to the lower two-thirds of the crypts rather than distributed throughout the height of the crypts as reported for adenomatous epithelium.
Carcinogenesis 1991 Nov
PMID:Dose response and proliferative characteristics of aberrant crypt foci: putative preneoplastic lesions in rat colon. 193 94

Retinoblastoma gene has been cloned, and gene product has been characterized precisely. Recently, Wilms' tumor gene has been cloned, and interestingly, its expression was found in genitourinary system, suggesting that anomaly of this system was due to WT gene itself. Molecular analysis performed in colon cancer suggested that several tumor suppressor genes were involved in carcinogenesis and progression of this tumor. These findings revealed that tumor suppressor genes were involved in the development of adult cancer as well as childhood embryonal tumors. Chromosome abnormalities and tumor suppressor gene in childhood cancer are reviewed and referred to future prospects.
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PMID:[Chromosome abnormalities and tumor suppressor gene in childhood cancer]. 197 26

The objective of this study was to assess, in a controlled experimental system, whether the concentrations of polyamines (Pa) in urine or erythrocytes increase during the process of colon carcinogenesis in rats, and whether such changes reflect tumor volume. Colon carcinoma was induced in Sprague-Dawley rats by subcutaneous injection of 1, -2 dimethylhydrazine (DMH). 24-hour urine and blood samples were collected and analysed for their Pa consent, with high pressure liquid chromatographic method. The levels of any Pa derivatives in either urine or erythrocytes at 32 weeks after the administration of DMH were not significantly high compared with the control group at the same week. However, certain increases of Pa in erythrocytes were observed in the levels of putrescine (1.3 times), spermidine (1.3 times), and spermine (1.5 times) respectively compared with the control group and there were high positive correlations between tumor volume and the levels of each Pa derivatives. On the ground of the results, Pa in erythrocytes seems to be the sensitive parameter for tumor volume compared with Pa in urine.
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PMID:[Raised polyamines in erythrocytes of DMH administrated rats with colonic cancers and those relationship to tumor volume]. 203 May 57

We have previously reported a method for visualizing the mucosal surface of fixed unsectioned rodent colons at the crypt level and have identified lesions, termed aberrant crypt foci (ACF), in the colons of carcinogen-treated rodents. We hypothesized that ACF represent the precursor lesions (PL) of colon cancer. In the present study, the effect of feeding disulfiram (DSF) added to a semi-synthetic diet (0.5% or 1% by wt) on 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) induced ACF was investigated. DSF has been shown to inhibit DMH and AOM-induced colon cancer. Therefore, it was reasoned that if ACF represent PL then their induction and growth should also be inhibited by DSF. CF1 female mice were randomly divided into three groups of 30 each. Group 1 was fed a diet containing 1% DSF for 9 days prior to and 1 day after receiving a single i.p. injection of either DMH, AOM or saline. Group 2 was fed a diet containing 1% DSF for 9 days prior to and 14 days after receiving a single i.p. injection of DMH, AOM or saline, whereas group 3 received control diet throughout the experimental duration. All animals were killed 5 weeks after receiving the injections. It was observed that feeding DSF, for 9 days prior to and for either 1 day or 14 days after the administration of a single injection of DMH, resulted in a complete inhibition of ACF. DSF feeding for 9 days prior to and 1 day after AOM injection resulted in a significantly greater number of ACF compared to the control group (12 +/- 2.3 vs 7.2 +/- 1.2); whereas DSF feeding for a longer duration (i.e. 9 days prior to and 14 days after AOM treatment) was associated with a significantly lower number of ACF compared to those fed DSF for only one day after AOM treatment (4.1 +/- 0.6 vs 12.4 +/- 2.3) and a lower number compared to the control group (4.1 +/- 0.6 vs 7.2 +/- 1.2).
Carcinogenesis 1991 Jun
PMID:Effect of disulfiram on 1,2-dimethylhydrazine- and azoxymethane-induced aberrant crypt foci. 204 3

Effects of dietary calcium on mammary carcinogenesis in rats were investigated because of evidence that calcium counteracts the promotion of colon cancer by dietary fat and because experimental diets for rats normally contain higher amounts of calcium and vitamin D than do human diets. Our earlier experiments indicated that yields of tumors induced in young, Sprague-Dawley rats by 7,12-dimethylbenz(a)-anthracene (DMBA) were higher when dietary calcium, phosphate, and vitamin D were decreased. Results of an experiment in which dietary amounts of calcium, phosphate, and vitamin D were varied independently suggested that phosphate and vitamin D have interactive effects with calcium. Another experiment in which dietary vitamin D alone was varied provided evidence that higher amounts inhibited tumorigenesis in the presence of low amounts of calcium and phosphate but the results with a high-calcium and -phosphate diet were inconclusive. The findings suggest that low amounts of dietary calcium and vitamin D and high amounts of phosphate increase susceptibility to DMBA-induced mammary neoplasia.
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PMID:Calcium and carcinogenesis of the mammary gland. 205 63

The prevention of cancer by agents in our diet has led to the concept that oxygen radicals are a necessary component of a variety of human cancers including breast, colon and prostatic cancer. These cancers are putatively promoted by estradiol, bile acids and androgens. Epidemiological studies have shown that these cancers are suppressed in vegetarian populations. Vegetable components that may be responsible for this cancer prevention are Vitamin A, retinoids and protease inhibitors (PIs). These agents have been shown to suppress the formation of hydrogen peroxide in promoter-induced neutrophils. They also have been shown to block two-stage carcinogenesis and breast cancer when fed to animals. PIs also suppress experimentally-induced colon cancer and spontaneous liver cancer. Moreover, a new series of cancer-preventive agents, Sarcophytols (isolated by Fujiki and co-workers), are capable of suppressing two-stage carcinogenesis, breast and colon cancers in rodents when given in low concentrations. Sarcophytols were also active suppressors of H2O2 formation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced neutrophils. These observations point to an essential role of oxygen radicals in carcinogenesis. Suppression of the oxygen radical response of neutrophils in relation to cancer preventive agents is a facile assay of these important substances. The mechanism of action of oxygen radicals in promoting carcinogenesis is a multiple one, including: (1) activation of oncogenes, (2) modification of DNA bases, and (3) formation of single-strand breaks leading to poly(ADP)ribose polymerase activation.
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PMID:Prevention of cancer by agents that suppress oxygen radical formation. 206 Aug 47


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