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

Our previous work on protein kinase C (PKC) and colon cancer has shown altered levels of PKC activity in human colon tumors, as well as activation of PKC by colon tumor promoters such as bile acids. To understand further the role of PKC in colon carcinogenesis, we analyzed the expression of phorbin, a gene induced by PKC activation, in a series of different stages of human colon tumors. As shown by northern blot analyses of poly (A)+ RNA, higher levels of phorbin RNA were seen in 26 colon tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin RNA in the tumors and the extent of invasion (tumor-to-normal tissue phorbin RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin RNA was also abundant in a human colon cancer line (HT29). We also examined the expression of other mitogen-responsive genes (c-myc, ODC, and beta-actin) in a set of 19 colon tumor samples. All tumors displayed significant (mean 3.8-fold) increases in the level of c-myc RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these tumor samples also showed increased levels of ODC (mean 3.1-fold) and beta-actin (mean 1.6-fold) RNA, respectively. The increased levels of c-myc, ODC, and beta-actin RNA did not correlate with the extent of tumor invasion. Taken together, these results demonstrate that human colon tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin RNA suggest that this could serve as a useful biomarker in studies on human colon cancer.
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PMID:Increased levels of phorbin, c-myc, and ornithine decarboxylase RNAs in human colon cancer. 169 76

alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including breast, urinary bladder, and colon. This study was designed to determine whether DFMO treatment can inhibit tumor growth on chemical-induced colon cancer in rats. Effectiveness of DFMO in combination with mitomycin C (MMC) was also evaluated. Forty-two Sprague-Dawley rats received dimethylhydrazine (20 mg/kg) s.c. once weekly for 20 wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into four groups that were subjected to the following treatment: none; DFMO alone; MMC alone; and a combination of DFMO plus MMC. After 5 wk of treatment, the barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. The mean tumor doubling time in the control group was 20.7 +/- 9.1 days (SD). "Response" was judged as effective when tumor doubling time in treatment groups was more than 38.9 days, calculated from the mean + 2 SDs in the control group. Response rates in the DFMO, MMC, and DFMO plus MMC groups were 40.0%, 10.0%, and 82.3%, respectively. DFMO was a more effective inhibitor of tumor growth than MMC, and DFMO in combination with MMC resulted in a synergic diminution of tumor growth. The double-contrast barium enema is useful to observe sequential tumor growth and may be appropriate for the evaluation of new treatment on experimental colon cancer in rats.
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PMID:Reduced growth rate of dimethylhydrazine-induced colon tumors in rats. 173 57

The proposed intermediate steps in the relationship between a diet-dependent increase in colonic bile acids and proliferation of colonic cells were studied in rats. Male Wistar rats were fed diets supplemented with increasing amounts of steroids to increase the bile acid concentration of the colon. After 2 weeks, in vivo colonic proliferation was measured using tritiated thymidine incorporation into DNA. Luminal lytic activity was measured as lysis of erythrocytes by fecal water. To quantify hemolysis in the presence of fecal water, a method was developed which measures Fe-release using atomic absorption spectrophotometry. This method proved to be superior to the cell-counter method published earlier. Our results showed that steroid supplementation increased, in a dose-dependent manner, the total fecal and the soluble bile acid concentration as well as lytic activity of fecal water and colonic proliferation. A highly significant correlation between lytic activity of fecal water and colonic proliferation (r = 0.85, n = 24, P less than 0.001) was observed. These results indicate that the increase in colonic proliferation is mediated by diet-dependent increases in soluble colonic bile acid concentration and luminal lytic activity. This sequence of effects illustrates how diet could influence the risk for colon cancer.
Carcinogenesis 1992 Jan
PMID:Diet-induced increase of colonic bile acids stimulates lytic activity of fecal water and proliferation of colonic cells. 173 71

We have been studying a rat model of colon cancer in which tumors are induced by direct application of N-methyl-N-nitrosourea (MNU) to discrete areas of the colonic mucosa for a limited period of time. Activation of the ras genes by point mutation has been observed in many experimental tumors, including tumors induced by MNU. To detect potential activating point mutations in the H-ras and K-ras oncogenes in MNU-induced rat colon tumors, DNA samples from 40 adenomas, nine carcinomas, and 14 histologically normal tissue samples from 14 rats--as well as from 16 foci induced on NIH3T3 cells by tumor DNAs--were amplified by the polymerase chain reaction and hybridized with allele-specific oligonucleotide probes. No H-ras point mutations were observed in any of these samples. We did detect K-ras point mutations, however, in four primary tumours--one adenoma (2.5%) and three carcinomas (33%); these mutations were all G----A transitions at the second nucleotide of codons 12 and 13. The absence of detectable ras mutations from the majority of tumors suggests that, in contrast to other animal models utilizing MNU, tumorigenesis in MNU-induced rat colon tumors may predominantly involve activation of genes other than ras.
Carcinogenesis 1992 Jan
PMID:K-ras oncogene mutations in rat colon tumors induced by N-methyl-N-nitrosourea. 173 72

Carcinogen-induced aberrant crypts (AC) of the colon are a precancerous state that leads to malignancy. The inhibition of AC formation by chemopreventive agents was evaluated in this study. Colon AC were induced by 1,2-dimethylhydrazine (DMH) in 3 weeks in CF1 mice. The cecum of the large intestine of CF1 mice did not produce more than one AC focus per animal. The effect of DMH and that of the inhibitors in this part of the large bowel were essentially similar to the vehicle control and inhibitor-only controls. The response of DMH treatment in the colorectal portion of the large bowel was found to be different from that of the cecum. The DMH treated mice had 13-17 foci per animal in three different experiments. The average number of AC per focus was greater than one in all three experiments performed. None of the inhibitor-only control animals nor the cottonseed oil vehicle control animals developed AC focus in the colorectal or the cecal part of the large bowel. The known inhibitor of colon carcinogenesis 3-butyl-4-hydroxyanisole reduced DMH-induced average AC formation by 10 and 46% at 1 and 4 mg per dose, respectively. The inhibitors 2-n-butylthiophene and phenylpropylisothiocyanate reduced DMH-induced average AC formation greater than 34 and greater than 40% respectively. The postulated inhibitor 2-n-octylthiophene, which is an eight-carbon homolog of 2-n-butylthiophene, similarly reduced DMH-induced AC formation. The known colon carcinogenesis inhibitor dehydroepiandrosterone, in contrast, has no effect. The inactivity of dehydroepiandrosterone to inhibit colon AC formation was attributed to its mechanism of inhibitory action, which differs from that of the phenol, isothiocyanate and thiophenes. The short duration that is required to produce quantifiable results suggests that the reduction of carcinogen-induced AC formation may be developed into a useful prescreening assay for potential chemopreventive agents against colon cancer.
Carcinogenesis 1991 Dec
PMID:Reduction of aberrant crypt formation in the colon of CF1 mice by potential chemopreventive agents. 174 33

Gastrin is trophic to colon cancers that possess gastrin receptors. Whether fasting serum gastrin concentrations are high in patients with colon cancer is controversial. We therefore studied the effect of food on serum gastrin concentrations in patients with colon cancer and control subjects. Fasting serum gastrin was greater, though not significantly so, in patients with colon cancer before surgery (mean (SD) 17.4 (3.6) pmol/l, n = 16) compared with control subjects (12.6 (1.9) pmol/l, n = 14). Postprandial increases in serum gastrin were significantly and persistently higher than normal in the cancer patients. These increases were due to a subset of six patients with serum gastrin concentrations greater than the control mean + 2 SD at 20 and 40 minutes (62 pmol/l-146 pmol/l). Four of the six patients had intra-abdominal metastases. The extent of the increase may well correlate with that of the disease. Surgical resection of the tumour resulted in a fall in serum gastrin values and probably reflects the cause of the hypergastrinaemia. Hypergastrinaemia may, therefore, be an important aetiological factor in colon carcinogenesis.
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PMID:Postprandial hypergastrinaemia in patients with colorectal cancer. 175 67

Azoxymethane (AOM) is commonly used in colon carcinogenesis studies in rodents. In an attempt to develop a large animal model of human colon cancer, AOM was given to Hanford-Moore miniature pigs. Six pigs were injected intraperitoneally with a single dose of AOM of either 5, 10, 20, 40 or 55 mg per kg body weight. Within 48 h, severe signs of toxicity and death occurred in animals receiving greater than 20 mg per kg AOM. After 30 days, all surviving animals were killed and necropsied. Acute hepatic necrosis with haemorrhage was the major toxic effect of AOM in all animals receiving doses exceeding 20 mg per kg. In a second, longer-term experiment, eight pigs were injected with either 20 mg per kg AOM weekly or 10 mg per kg AOM every other week or a combination of both treatments. Chronic toxic effects were limited to the liver. No colon tumours were observed. It is concluded that this particular species demonstrates marked hepatic sensitivity to the toxic effects of AOM.
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PMID:Hepatic pathology of the colon carcinogen, azoxymethane, in Hanford-Moore miniature pigs. 176 59

The role of selected histopathological methods was evaluated for the characterization of tumourous tissues resulting from chemically induced carcinogenesis in rats. Colon cancer was induced by treating rats with a direct carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), alone or with subsequent treatments with secondary bile acids. Morphological studies showed that the tumorigenic effect of MNNG resulted in changes in the shape of the crypts, disappearance of mucous (goblet) cells, and marked increases in the mitotic index, the size of nuclei and the number of aberrant nuclei. A significant number of lymphocytes infiltrated between the crypts and into their lumens. A sharp decrease in concentrations of neutral mucopolysaccharides and sulfomucins and an increase in the amount of vic-glycol groups and nonsulfated mucosubstances were demonstrated in tumourous epithelial cells. A moderate positive reaction to tissue polypeptide antibody was observed in these cells. The tumor-promoting effects of secondary bile acids were detected morphologically by an increase in the amount of connective tissue that infiltrated newly formed tumors. The increased number of micronuclei in otherwise histologically unaltered colon tissues adjacent to a tumor suggests that these regions represent a precancerous stage in the development of tumors. The important role of morphological methods in the evaluation of the effects of carcinogen and tumor promoters and in the detection of various phases in experimental carcinogenesis was discussed.
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PMID:Role of morphological methods in the analysis of chemically induced colon cancer in rats. 183 46

Incident cases of large bowel cancer from the Swiss canton of Vaud over the period 1974-88 were analyzed in relation to the distribution of site by sex, age, marital status and detailed subsite. A total of 1,968 cases were registered in males and 1,958 in females, corresponding to overall age-standardized (world) rates of 32.2/100,000 males and 22.4/100,000 females. The frequency of ascending and transverse colon cancer was lower in males (18.2% and 9.3%) than in females (23.1% and 10.0%, respectively), but cancers of the sigmoid colon and rectum were proportionally more frequent in males (34.0 and 30.0% versus 29.9 and 24.6% in females). Anal cancer accounted for 4.0% of large bowel cancers in females, but only 1.2% in males. Analysis of age-specific rates showed comparable values for ascending colon cancer in both sexes and in relation to each subsequent age group, as well as in sigmoid and rectal cancers up to middle age, while a male excess for the latter cancers became evident after age 55. A female excess for anal cancer was apparent in any subsequent age group. Information on marital status was available on 2,398 decreased subjects. Never married cases accounted for 12.2% of women and 8.1% of males. The excess of unmarried women was somewhat larger in the colon than in the sigma and rectum groups, but there was no evidence of excess of never married females for anal cancer. These data confirm that there are appreciable intersex heterogeneities in the descriptive epidemiology of various subsites of large bowel cancer, as well as complex interactions between sex and age, which may be related to female hormone correlates of intestinal carcinogenesis. Whatever the main biological mechanism(s), these data show noticeable similarities for both sexes in the descriptive epidemiology of cancers arising in the left colon and rectum, but noticeable differences with the right colon. Even more substantial are the differences with anal cancer, which should be linked to its venereal correlates.
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PMID:Patterns of large bowel cancer by subsite, age, sex and marital status. 186 55

A quantitative overview of 14 studies of rat colon carcinogenesis was undertaken to examine the relationship between fat intake, and fat intake by degree of saturation, on the incidence of colon carcinoma while controlling for calorie consumption. Calorie consumption was not recorded in 11 of the 14 studies. Hence, two types of analyses were conducted. The first examines carcinoma incidence as a function of percent fat (by weight), with calories controlled for by including weight gain per week in the analysis. The second estimates calories per day, for studies not providing such information, using weight gain per week and age at death, followed by a joint analysis of estimated fat calories and estimated total calories. With either approach, a rather strong positive relationship between colon carcinoma incidence and fat intake is indicated for Fischer 344 rats, but no association is apparent for Sprague-Dawley rats. This situation is somewhat clarified when the degree of saturation is taken into account: both strains gave results that suggest a negative relationship between colon cancer incidence and omega-3 fatty acids intake and a positive relationship with non-omega-3 polyunsaturated fat intake among Fischer 344 rats. These analyses suggest an important and specific role for dietary fat in the promotion of rat colon carcinoma.
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PMID:Quantitative review of studies of dietary fat and rat colon carcinoma. 186 11


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