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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile acids were been implicated in several pathologic processes, such as secretory diarrhea, carcinogenesis, and immunomodulation of human peripheral blood lymphocytes. Nevertheless, their effect on the human gut immune system is not known. In this study we investigate the effect of several bile acids (cholate, deoxycholate, chenodeoxycholate) and 13-hydroperoxylinoleic acid (conc. 0.1-1000, microM) on human colonic lamina propria lymphocyte (LPL) DNA synthesis and cell proliferation. In addition, the effect of these bile acids on LPL ornithine decarboxylase activity was also determined. Significant dose-dependent inhibition of [3H]thymidine incorporation in Con A-stimulated LPL was observed. Parallel inhibition was seen on LPL cell proliferation. Furthermore, bile acids inhibited ornithine decarboxylase activity in Con A-stimulated LPL. These effects on cell proliferation were not due to the LPL cytolysis as viability and cell membrane integrity were not altered. Our results suggest that bile acid has an immunoregulatory function on the human mucosal immune system and may have a role during pathological states.
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PMID:Modulation of human colonic lamina propria lymphocyte proliferation. Effect of bile acids and oxidized fatty acids. 230 78

Life-long bowel habits of 685 colorectal cancer cases and 723 age/sex frequency matched community controls were investigated as one part of a large, comprehensive, population-based study of colorectal cancer incidence, etiology, and survival, The Melbourne Colorectal Cancer Study. Self-reported chronic constipation was statistically significantly more common in cases than in controls (P = .05). Three or more bowel actions per day were reported by more cases than controls but the total number of respondents in this subset consisted of only ten cases and two controls. Otherwise, the frequency and consistency of bowel motions was similarly distributed among cases and controls. Constipation disappeared as a significant risk when simultaneously adjusted for previously determined dietary risk factors, indicating that it is the diet and not the constipation that is associated with the risk of large-bowel cancer. Additionally, a highly statistically significant association (P = .02) was found with the risk of colorectal cancer in those who reported constipation and also had a high fat intake, a finding consistent with current hypotheses of colorectal carcinogenesis. It is concluded that chronic constipation, diarrhea, and the frequency and consistency of bowel motions, as well as laxative use, are unlikely to be etiologic factors in the development of colorectal cancer. Self-reported chronic constipation is a marginally significant indicator of excess risk of large-bowel cancer and may be used as one of the indices in the screening of individuals for this cancer.
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PMID:The role of chronic constipation, diarrhea, and laxative use in the etiology of large-bowel cancer. Data from the Melbourne Colorectal Cancer Study. 339 Oct 59

The effect of croton oil on intestinal carcinogenesis by methylazoxymethanol acetate (MAM) was examined in ACI/N rats. Twenty seven male and 28 female ACI/N rats were given a single intragastric intubation of MAM at a dose of 25 mg/kg body weight, followed by croton oil at 0.25 ml/kg body weight, 3 times a week, by gastric intubation until the termination of this experiment (365 days). The animals had diarrhea with administration of the croton oil, but the diarrhea had no effect on their gain in weight. Rats from all groups surviving more than 216 days were counted as effective animals. Seventeen out of 54 effective rats which were treated with MAM and croton oil developed intestinal tumors and the incidence of the intestinal tumors was significantly less than that of the group treated with MAM alone (30 out of 50 rats, P less than 0.01). The average number of tumors per rat in the experimental group which was treated with MAM and croton oil (0.6 +/- 1.1) was also smaller than that in the group which was treated with MAM alone (1.0 +/- 1.8), although the difference was not significant. These results suggest that croton oil may suppress some tumor growth at the proper dose in intestinal carcinogenesis which is initiated by MAM.
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PMID:Suppressing effect of croton oil on intestinal carcinogenesis induced by methylazoxymethanol acetate in rats. 362 8

A 3-year-old male grey collie and 4-year-old female grey collie were part of a cyclic hematopoiesis study. Both dogs had experienced numerous bacterial infections, and both dogs were receiving various treatment regimens, including lithium and hematopoietic growth factors, to control the cyclic hematopoiesis. The first dog was presented in acute collapse and had a rapid clinical course. The second dog was presented with pyrexia and subsequently developed anorexia, disorientation, tremors, mild diarrhea, and bruising at venipuncture sites. Postmortem examination revealed pancreatic adenocarcinoma with metastasis in both cases. Pancreatic adenocarcinoma is a rare neoplasm in dogs. The incidence of pancreatic adenocarcinoma noted in this report is more than 150 times that previously reported in dogs. The cause of the increased incidence of pancreatic malignancy in these grey collies is unknown; possible factors include chronic inflammation or infections, chronic drug therapy, or genetic predisposition. Development of an uncommon neoplasm in two young grey collies may offer an opportunity to study the mechanisms of carcinogenesis.
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PMID:Pancreatic adenocarcinoma in two grey collie dogs with cyclic hematopoiesis. 747 71

Colonic SCFA formation from fermentable carbohydrate is important for the maintenance of morphologic and functional integrity of the colonic epithelium. Carbohydrate-induced diarrhea occurs when the amount of carbohydrate entering the colon exceeds its fermentation capacity. Deficient availability or utilization of SCFA, mainly of n-butyrate, is the cause of diversion colitis and may play important roles in colonic carcinogenesis, in starvation and enterotoxigenic diarrhea, and in idiopathic UC.
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PMID:Colonic fermentation: metabolic and clinical implications. 786 76

Induction of cell proliferation by laxatives and related compounds in rat intestines was analysed by BrdU-labelling and compared with histopathological changes in the mucosa and findings for feces. Male F344 rats were fed a diet containing danthron, sennosid A, bisacodyl, 1-hydroxyanthraquinone (1-HAQ), magnesium sulfate (MgSO4), dextran sulfate sodium (DSS), pectin, carboxymethylcellulose sodium (CMC-Na) or sodium chloride (NaCl) for 7 days. The stimulant laxatives, danthron, sennosid A and bisacodyl, significantly induced cell proliferation in almost the entire intestinal epithelia in a clear dose-dependent manner. DSS also induced cell proliferation in some portions at high doses. Increase in BrdU-labelling indices was correlated well with the severity of inflammatory changes in the intestinal mucosa as well as with purging effects of stimulant laxatives and DSS. In contrast, the bulk-forming laxative CMC-Na did not consistently enhance cell proliferation nor cause apparent cytotoxicity in the intestine despite exerting remarkable purging effects. 1-HAQ and MgSO4 slightly induced cell proliferation in the cecum and the colorectum, although there was little or no intestinal cytotoxicity. Pectin and NaCl did not influence cell kinetics of the epithelia, nor cause any inflammatory changes in the mucosa. Our results thus indicate that diarrhea caused by laxatives is not necessarily correlated with induction of cell proliferation, as in the intestinal mucosa, and that inflammatory changes followed by regenerative process could be responsible for enhancing cell kinetics. Although the precise significance of cell proliferation in carcinogenesis remains unclear, it is crucial for setting doses of carcinogenicity testings that charges in cell kinetics caused by chemicals be taken into account.
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PMID:Cell proliferation induced by laxatives and related compounds in the rat intestine. 806 33

Bifidobacterium longum has been shown to afford protection against colon tumorigenesis. Lactulose, a keto analog of lactose, serves as a substrate for preferential growth of Bifidobacterium. It is not known whether feeding lactulose along with B. longum will have any advantage over feeding of B. longum alone. To test this combination effect, 61 male Fisher 344 weanling rats were divided into four groups of 15 rats each (16 in the control group) and assigned to one of the following four diets for 13 weeks: (i) AIN76A (control, C); (ii) C + 0.5% B. longum (C+Bl, containing 1 x 10(8) viable cells/g feed); (iii) C + 2.5% lactulose (C+L); (iv) C + 0.5% B. longum + 2.5% lactulose (C+Bl+L). All animals received a s.c. injection of azoxymethane at 16 mg/kg body wt at 7 and 8 weeks of age. Colons of 10 rats from each dietary group were analyzed for aberrant crypt foci (ACF), which are preneoplastic markers. Colonic mucosa and livers from five rats were analyzed for glutathione S-transferase (GST, a Phase II enzyme marker). Results indicate that feeding of lactulose and B. longum singly and in combination reduces the number of ACF (P = 0.0001) and the total number of aberrant crypts significantly (P = 0.0005). The total number of ACF in diets C, C+Bl, C+L and C+Bl+L were 187 +/- 9, 143 +/- 9, 145 +/- 11 and 97 +/- 11 respectively. There was no significant difference in weight gain among treatments. Colonic mucosal GST levels were significantly (P = 0.05) higher in the Bl and L groups compared with group C. Initially there was a mild diarrhea in lactulose-fed rats. There was a positive correlation between higher cecal pH and number of ACF. Results of the study indicate that Bifidobacterium and lactulose exert an additive antitumorigenic effect in rat colon.
Carcinogenesis 1997 Mar
PMID:Bifidobacterium longum and lactulose suppress azoxymethane-induced colonic aberrant crypt foci in rats. 906 51

In industralized countries, 70 to 80% of children with cancer can be cured by expensive interdisciplinary teamwork and by cooperation on the national or international level. As a result of poor socio-economic conditions, worldwide, less than 20% of the approximately 185,000 children developing cancer each year get adequate treatment. This is also true for 14 to 15 million children dying each year of diarrhea and infections, but while this number is decreasing, the number of children with cancer is increasing. In "middle income" developing countries, cancer is now a leading cause of death for children between 5 and 15 years of age. The "geography" of pediatric cancer reveals complex interactions between environment, lifestyle, and carcinogenesis. The "mapping" of pediatric cancer is far from complete, and the investigation of carcinogenetic interactions has barely started. A great challenge is the planning of pediatric oncology in developing countries. The goals are to improve the access to treatment and treatment results. Even if pediatric oncology has a low priority, the institution, in each country or large province, of at least one pediatric cancer unit may improve not only cancer treatment but medical care in general. By promoting education, organizing meetings, and setting minimum standards for training and care, international organizations can contribute to the development of pediatric oncology worldwide.
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PMID:The problem of pediatric malignancies in the developing world. 938 44

Mice deficient in both interleukin-2 and beta 2-microglobulin expression (Beta 2mullnull x IL-2null mice) develop an inflammatory disease of the colon resembling ulcerative colitis. To examine long-term complications of disease in these mice, a group of 34 Beta 2mnull x IL-2null mice was monitored for 6-12 months. Development of clinical disease was assessed by wasting, general appearance, and diarrhea. Further analysis included histologic examination of the distal colon for colitis, staining of CD4+ T cells for surface activation markers, and cytoplasmic staining of CD4+ T cells for IFN-gamma and TNF-alpha. These older Beta 2mnull x IL-2null mice had activated CD4+ T cells as assessed by surface markers on flow cytometry. Cytoplasmic staining revealed IFN-gamma production, but not TNF-alpha production by CD4+ T cells. The majority of these older Beta 2mnull x IL-2null mice continued to have colitis on histology. However, they lived much longer and had less wasting in comparison to IL-2null mice. At necropsy, 11 (32%) of 34 of the Beta 2mnull x IL-2null mice had tumors in the proximal half of the colon. Histologic examination confirmed these tumors to be adenocarcinomas. These mice may be useful as a model for studying carcinogenesis in chronic colitis.
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PMID:Development of colonic adenocarcinomas in a mouse model of ulcerative colitis. 974 Oct 21

Retinoids have been shown to be potent inhibitors of epithelial carcinogenesis. Recent evidence has demonstrated that retinoid actions are mediated through nuclear receptors, which are proteins encoded by the retinoic acid receptor and retinoid X receptor gene families. These receptors are activated by binding to specific retinoids; of the known naturally occurring retinoids, 9-cis retinoic acid is unique in its ability to bind to both receptor families. Because of its unique receptor-binding characteristics, 9-cis retinoic acid may have biological activity not possible with other retinoids. For this reason, we conducted a Phase I trial of 9-cis retinoic acid in adult patients with solid tumors. Twenty-two patients were treated twice daily with p.o. 9-cis retinoic acid at doses ranging from 20 mg/m2/day to 150 mg/m2/day. The patients had non-small cell lung cancer (n = 8), breast cancer (n = 5), colorectal cancer (n = 3), head and neck cancer (n = 2), nonmelanoma skin cancer (n = 2), or ovarian cancer (n = 2). The dose-limiting (WHO grade III) toxic effects, which occurred at the 150-mg/m2/day dose level, were headaches and diarrhea. Less severe (grades I and II) toxic effects included cheilitis, dry skin, conjunctivitis, fatigue, hypertriglyceridemia, alkaline phosphatase elevation, myalgia/arthralgia, and hypercalcemia. Of the 15 patients evaluable for tumor response, no objective responses were observed. Pharmacokinetic analysis revealed a reduction in peak 9-cis retinoic acid plasma levels with chronic administration. Based on this study, the recommended Phase II dose of 9-cis retinoic acid in adult patients with solid tumors is 100 mg/m2/day administered in a divided dose twice daily.
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PMID:Phase I trial of 9-cis retinoic acid in adults with solid tumors. 981 71


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