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)

It has been reported previously that populations with a decreased concentration of fecal bile acids have a lower incidence of colon cancer. We examined the importance of fecal bile acid dilution by wheat bran (WB) in inhibiting colonic tumorigenesis in an experimental animal model. Male F344 rats received oral doses of the colon carcinogen 1,2-dimethylhydrazine [CAS: 540-73-8] and were assigned randomly to groups fed one of four semipurified diets for 26 weeks. The diets were fiber-free (FF), 10% WB, FF + bile salts, or WB + bile salts. The amount of bile salts added was adjusted to produce a fecal bile acid concentration in the group fed WB + bile salts equal to that found in the FF groups. Fecal bile acid concentrations at 12 and 24 weeks in the WB + bile salts group were similar to those in the FF group. Gross and microscopic findings at necropsy revealed a reduced total number and multiplicity of colon tumors in both bran-fed groups. Although the fecal bile acid concentrations of the FF and WB + bile salts groups were equal, the latter showed a significant reduction in tumor yield.
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PMID:Reduction of colonic carcinogenesis by wheat bran independent of fecal bile acid concentration. 282 14

The effects of ad libitum feeding of a chemically defined diet in liquid form on the incidence and histology of colon cancer induced by 10 weekly sc injections of 7.4 mg/kg of azoxymethane [(AOM) CAS: 25843-45-2] were investigated in W-rats. The chemically defined diet was adjusted once every 24 hours from 4 weeks before injection of the carcinogen to the end of the experiment at week 40. Oral administration of the defined diet resulted in significant increase in the incidence of colon cancer at week 40. Histologic examination showed that unlike adenocarcinomas with high mucin-producing activity, which were common in rats on pellet diet, most of the adenocarcinomas that developed in rats fed on defined diet were highly or well differentiated, with a typical glandular pattern. Administration of the chemically defined diet also resulted in marked colon mucosal hypoplasia and reduced gastrin levels in the serum at weeks 4 and 40.
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PMID:Effect of a chemically defined diet in liquid form on colon carcinogenesis in rats. 299 35

Liver metastases were produced in syngeneic BD IX rats by intraportal injection of colon cancer cell aggregates. The cells originated from the DHD/K12 cell line, derived from a 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon adenocarcinoma in BD IX rats. The animals received either cyclosporine A (CSA) or the excipients alone (control) through daily gastric intubation during 6 weeks. Multiple and very large hepatic metastases were observed early in 100% of the CSA-treated rats. The mean tumor volume was approximately 2,000 times higher in the CSA-treated group than in the controls (P less than .01). Survival time in the CSA-treated group was shortened (P less than .01) by generalized metastatic disease. Easy production of metastasis from colon cancer in 100% of the animals and precise estimation of tumor volume may prove useful for future therapeutic studies of secondary hepatic disease.
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PMID:Quantitative study of liver metastases from colon cancer in rats after treatment with cyclosporine A. 345 15

The effects of multiple dietary influences on 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]-induced colon cancer in rats were studied. A 2(4) factorial experimental design was used to examine the main and interactive effects of 15% wheat bran (WB), 1% cholesterol (CH) with cholic acid, 20% beef tallow (BT), and 0.1% indole-3-carbinol (IC) on 160 male F344 rats treated ip with DMH (10 mg/kg) weekly for 16 weeks. The test diets were fed for 3 weeks before, 16 weeks during, and 12 weeks after DMH administration. At necropsy, total weight gain, liver and spleen weights, serum CH levels, liver aryl hydrocarbon hydroxylase (AHH) activity, and the size, number, incidence, and location of intestinal tumors were analyzed for dietary factor effects. The most significant inducer of tumors was the combination of CH + BT + IC acting in synergism. The single main effect most responsible for tumor morbidity was IC, which appeared to enhance tumorigenesis via its role as an inducer of AHH activity. The WB decreased tumor incidence and burden when added to diets also containing CH, but it otherwise increased tumor burden per tumor-bearing animal and incidence in all other diets. This study demonstrated the need for examining synergistic and antagonistic interactions among dietary initiators and/or promoters of colon carcinogenesis, as well as implicating IC as a significant factor in the development of DMH-induced tumors in rats.
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PMID:Multiple dietary factors in the enhancement of dimethylhydrazine carcinogenesis: main effect of indole-3-carbinol. 345 19

The effect of dietary beta-carotene on colon carcinogenesis induced by 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8] was studied in female inbred Swiss Webster (ICR) mice. At age 10 weeks and continuing throughout the experiment, mice received diets consisting mainly of natural foods (laboratory chow) and containing 2 or 22 mg beta-carotene/kg. At age 15 weeks they received 7 weekly sc injections of DMH (total dose: 196 mg DMH X diHCI/kg body wt). When autopsied 31 weeks after the first DMH injection, the incidence (percent of mice with tumors) and multiplicity (number of tumors/tumor-bearing mouse) of colon tumors were reduced by half in the mice supplemented with beta-carotene. There was a much greater decrease in adenocarcinomas than in adenomas. Mice observed for 13 additional weeks revealed that the mortality rate, due largely or wholly to colon cancer, was only about half in supplemented mice. Mice sacrificed 12 weeks after the first dose of DMH (i.e., well before tumors appeared) showed mild colon mucosal hyperplasia. beta-Carotene supplementation, however, did not alter this, indicating that the protective effect against colon cancer may have occurred at a late stage of carcinogenesis.
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PMID:Protective effect of beta-carotene against colon tumors in mice. 347 57

Primary gastrointestinal tumors were induced in male WF rats by 16 weekly sc injections of 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8; 20 mg/kg/wk]. Twenty-four to 28 weeks after the start of DMH injections, all rats were surgically explored and gastrointestinal tumors were resected. Rats with no remaining microscopic disease after operation were immunized with one of four tumor isografts. The first isograft, DMH-W163, is a poorly differentiated mucinous adenocarcinoma explanted from a colon cancer in a DMH-treated animal. It has been shown to possess antigens that cross-react with other DMH-induced bowel adenocarcinoma isografts. The second isograft, DMH-W49, is a carcinosarcoma explanted from a DMH-treated primary colon cancer. It has intermediate antigenic cross-reactivity with other colon adenocarcinoma isografts in the WF model. The third isograft, DMH-W15, is a sarcoma explanted from a DMH-induced colon cancer that does not possess antigens cross-reactive with other DMH-induced colon adenocarcinomas. The fourth isograft, SPK, is a spontaneous (non-DMH-induced) renal cell carcinoma that is immunogenic but should not contain tissue-type-specific antigens cross-reacting with the bowel cancers. Immunized rats received three sc weekly injections of 1 X 10(3) irradiated cells. Concomitant control rats received no immunization after resection of the primary tumor. Within 24 weeks of primary tumor resection, 12 of 16 (75%) rats not immunized had tumor recurrence. Only 8 of 24 (34%) rats immunized with DMH-W163 had tumor recurrence (P less than .025 compared to controls). Fifty percent of animals (10/20) immunized with the carcinosarcoma DMH-W49 had a recurrence. Animals immunized with the non-cross-reacting DMH-W15 sarcoma isograft had a recurrence rate similar to that of controls (16/20, 75%). The rats immunized with SPK were not protected from recurrence. Twelve of 19 (63%) had a recurrence at or near the suture line within 24 weeks following primary tumor resection. These results confirm that adjuvant immunotherapy can decrease the rate of recurrence following primary tumor resection in this model. In addition, immunogens that possessed tissue-type-specific antigens were more effective in preventing tumor recurrence than those that did not.
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PMID:Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2-dimethylhydrazine-induced bowel cancer. 659 Sep 17

The histogenesis of large intestinal carcinomas was studied by use of a low dose (2 mg/kg/wk) of azoxymethane [(AOM) CAS: 25843-45-2] administered im to inbred F344 rats. No evidence of benign polyp was seen, and the carcinomas in this model did arise directly from the flat mucosa. In marked contrast to the standard dose (8 mg/kg/wk) studies, low-dose AOM carcinogenesis yielded the following unusual features: a) There was a very high incidence of readily metastasizing mucinous adenocarcinomas that were extremely aggressive and easily transplantable; b) the carcinomas, microscopic and macroscopic, were localized predominantly in the proximal large intestine; c) foci of atypical early neoplastic (or so-called dysplastic) crypts as well as early carcinomas were frequently associated with the lymphoid aggregates in the intestinal wall; d) Paneth cells were commonly seen to be associated with these atypical crypts and/or early carcinomas associated with the lymphoid aggregates; and e) there was a virtual lack of the dilated, distorted, or hyperdistended crypts in noncarcinomatous epithelia. The significance of the lack of dilated, distorted, hyperdistended crypts and the similarity of this finding with the findings in the low incidence of colon cancer in the Japanese population are discussed.
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PMID:Large intestinal carcinogenesis. II. Histogenesis and unusual features of low-dose azoxymethane-induced carcinomas in F344 rats. 659 40

The CAS (cellular apoptosis susceptibility) gene is the human homolog of the yeast chromosome segregation gene CSE1. CAS may have a dual function in mammalian cells, one in apoptosis and another in cell proliferation. We have now mapped the CAS gene to chromosome 20q13. This region is known to harbor amplifications that correlate with aggressive breast cancer. Southern hybridizations with a CAS cDNA fragment and fluorescent in situ hybridization (FISH) with a P1 clone containing the CAS gene show elevated copy numbers in one leukemia, three of four colon, and in three of seven breast cancer cell lines. Elevated CAS copy number in CEM leukemia and COLO201 colon cancer cells was attributable to additional copies of chromosome 20. In SW480 and COLO205 colon cancer cells CAS is part of aberrant chromosomes containing large parts of 20q. In breast cancer cells CAS is also part of aberrant 20q chromosomes (MDA-MB-157 and UACC-812) or of additional 20q isochromosome in MDA-MB-134. In MDA-MB361 and BT-474 breast cancer cells CAS is separated from other markers centromeric and telomeric of CAS on 20q. MDA-MB 361 contains one additional copy of CAS, separated from the centromeric 20q control probe. BT-474 cells have up to 12 additional CAS copies that we separated from nearby telomeric and centromeric probes on 20q and that are translocated to abnormal chromosomes.
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PMID:The human CAS (cellular apoptosis susceptibility) gene mapping on chromosome 20q13 is amplified in BT474 breast cancer cells and part of aberrant chromosomes in breast and colon cancer cell lines. 896 95

Both suppressor oncogene and proliferative activity are believed to indicate colon cancer risk. The retinoblastoma (Rb) gene is a suppressor oncogene affecting cell differentiation. Retinoblastoma gene inactivation is associated with tumour development. However, the relation of the Rb protein to cell proliferation and colon tumour formation is unknown. Retinoblastoma protein quantity was correlated with proliferative activity in flat, unaffected mucosa specimens from 36 cancer patients, 21 non-cancer control subjects and in 29 tumour tissue samples from cancer patients. Nuclear Rb protein was measured by using automated CAS-200 image analysis of monoclonal antibody labelled frozen sections from fresh, surgically removed tissue. All colon cells within 15 whole crypts were imaged. Proliferative activity was also measured by using analysis with Ki-67 monoclonal antibody. Retinoblastoma protein content correlated directly with proliferative activity in flat mucosa of non-cancer control subjects (r = 0.63; P < 0.001; n = 21). A significant correlation was also found in flat mucosa specimens of non-metastatic (Duke's stages A and B) cancer patients (r = 0.52; P < 0.01; n = 22). However, Rb protein did not correlate with proliferation in flat mucosa from metastatic (Duke's stages C and D) cancer patients (r = 0.03; NS; n = 14) or in cancer tissue (r = 0.068; NS; n = 29). Mucosal Rb protein in the colon normally increases as proliferation increases. Dissociation between Rb protein and colon proliferation may occur in flat mucosa in patients with a higher risk of metastatic tumour growth. Future studies comparing Rb protein quantity and proliferative activity may help identify high-risk colon cancer patients.
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PMID:Colonic retinoblastoma protein and proliferation in cancer and non-cancer patients. 914 34

CSE1L/CAS (CAS) is a nuclear transport factor that plays a role in proliferation and apoptosis. The CAS gene consists of 25 exons. mRNA homologous over its entire length to the yeast homologue CSE1 is the predominant transcript in proliferating tissues. Additional mRNAs are generated by alternative splicing in a tissue-specific manner. An extended 3'-end is found in fetal and adult brain. A mRNA containing the 5'-end of CAS up to position 690 and an alternative 3'-end is expressed in trachea and encodes a truncated Ran-binding domain. Fetal liver expresses a mRNA with deletions of a central portion of CAS and additional sequences encoded by the last intron. SW480 colon cancer cells express another approximately 1500-base mRNA. Western blot analyses of various human tissues and immunohistology of mouse embryos show a correlation of CAS transcripts and CAS protein in different tissues. CAS isoforms may control nuclear transport of tissue-specific proteins.
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PMID:Tissue-specific alternative splicing of the CSE1L/CAS (cellular apoptosis susceptibility) gene. 1033 44


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