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PubMed · 16685383

Chronic colitis promotes tumor development.

Abstract

Patients with chronic ulcerative colitis have a significantly increased risk of colorectal cancer development. This study was aimed at clarifying whether colitis promotes tumor development or not. A dose of 200 mg/kg body weight 1,2-dimethylhydrazine was given to male Wistar rats. Four weeks later, 5% acetic acid (colitis group) or 0.9% saline (control group) was administered intrarectally once a week for 12 weeks and the rats were sacrificed after 27 weeks of dimethylhydrazine injection. Macroscopic lesions (ML) were more frequently detected in the colitis group than in the control group without statistical significance. However, the number of ML per rat with ML was largest in the colitis group (4.50 vs. 1.33; p=0.039). Eleven of 13 tumors were sessile in the colitis group, while three of five were pedunculated in the control group (p=0.044). All ML of 3 mm or more in diameter in the control group were intramucosal well-differentiated tumors. In the colitis group, 4 of 13 tumors were poorly or moderately differentiated or mucinous carcinomas, and 11 of 13 invaded the submucosal layer or deeper (p=0.003). The number of aberrant crypt foci per rat was smaller in the colitis group than in the control group. The number of crypt orifices was larger in the colitis group than in the control group (23.6 vs. 8.8: p<0.001). Significantly higher proliferative activity of normal-appearing mucosa was noted in the colitis group in all three parts of the colon. Colitis is suggested to promote colonic tumor development.

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BibTeXRIS

Masaru Shinozaki, Toshiaki Watanabe, Hajime Sato, Hirokazu Nagawa. 2006. Chronic colitis promotes tumor development.. https://pubmed.ncbi.nlm.nih.gov/16685383/

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Long term administration of granulocyte-macrophage colony stimulating factor decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats.

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1,2-Dimethylhydrazine↗

Survivin and Cyclooxygenase-2 are co-expressed in human and mouse colon carcinoma and in terminally differentiated colonocytes.

In the evolution of colon rectal cancer (CRC) the imbalance between cell proliferation and apoptosis is considered one of the prominent causes of tumor induction and/or progression. In order to establish the role of anti apoptotic proteins in colon cancer development, we studied with immunohistochemical techniques the expression of Survivin in a mouse model of colon carcinogenesis induced by 1,2-dimethyl-hydrazine treatment. In this mouse model Survivin was over-expressed during tumor development, showing a distribution mimicking that described in the correspondent human malignancies. We also correlated Survivin distribution with COX-2 and beta-Catenin expression patterns. The co-localization of COX-2/beta-Catenin/Survivin in the same epithelial cells in tumor samples lends credence to possible in vivo regulatory effects of COX-2 and beta-Catenin on the intracellular Survivin levels in mouse and human colon cancer.

1,2-Dimethylhydrazine↗

Intestinal MUC2 and gastric M1/MUC5AC in preneoplastic lesions induced by 1,2-dimethylhydrazine in rat: a sequential analysis.

Our study was performed to sequentially analyze the expression of the intestinal mucin MUC2 and of the gastric mucin MUC5AC as indicators during progression of preneoplastic biomarkers in rat colon. F344 rats were sacrificed 2, 4, 8, 12, 24 and 36 weeks after injection of 1,2-dimethylhydrazine (DMH, 200 mg/kg, i.p.). The expression of MUC2 and of MUC5AC was studied by immunohistochemistry in preneoplastic lesions classified in two categories: histologically altered foci (HAF) and beta-catenin accumulated crypts (BCAC). HAF appeared 4 weeks after DMH injection. Their crypt multiplicity stagnated with time (3-4 crypts/foci) but gastric MUC5AC mucin was always observed in some goblet cells of the lesions of this category. In contrast, MUC2-immunostaining was not modified compared to the adjacent crypts. Double-immunofluorescence revealed that goblet cells which produced MUC5AC continued to express MUC2. In BCAC, crypt multiplicity and mucin expression strongly evolved with time. These lesions were observed only 8 weeks after DMH-injection. At this stage, 20% of BCAC showed a decreased MUC2 expression and 33% were MUC5AC immunopositive. At the 36-week point, 43% of BCAC had a reduced MUC2 staining and 90% were positive for MUC5AC. This immunopositivity was often observed in all the cells of these lesions. Seldom, some BCAC were depleted at the same time in MUC2 and in MUC5AC. Similar alterations in mucin expression were observed in human colonic pre-neoplastic lesions. These findings suggest that a decrease in MUC2 expression and staining of MUC5AC in non-goblet-like cells predicts histological progression of preneoplastic lesions.

1,2-Dimethylhydrazine↗