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  • 1
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Downregulation of TGF-β receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF-β1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:We generated transgenic mice, called pS2–dnRII or ITF–dnRII, of which the dominant negative mutant of the TGF-β type II receptor was expressed under the control of tissue-specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA+ and VacA+) or administered with azoxymethane to determine the significance of loss of TGF-β signalling in gastrointestinal carcinogenesis.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Gastric adenocarcinoma developed in pS2–dnRII mice, whereas only chronic active gastritis was noted in wild-type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF-β signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen-labelling index when infected with H.pylori than wild-type littermates (P 〈 0.01). Development of colonic aberrant crypt foci was provoked in mice by intraperitoneal injections of azoxymethane, and ITF–dnRII mice showed significantly higher incidences of ACF and colon cancers than wild-type littermates.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Maintaining normal TGF-β signalling in the gastrointestinal tract seems to be important either for preventing abnormal mucosal proliferation, or for suppressing or retarding carcinogenesis.
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  • 2
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Long-term evaluation of gastric pathology after H. pylori infection is very important in order to reveal its clinical implications, since debate still exists on the gastric carcinogenesis provoked by H. pylori infection in animal models.Aim : Either to evaluate the long-term outcome of H. pylori infection or to determine how H. pylori could provoke gastric cancer in the mice model.Methods : Four-week-old specific pathogen free C57BL/6 mice (n = 115) were infected with SS1, the mouse-adapted H. pylori strain. After 4, 8, 16, 24, 36, 50 and 80 weeks of bacterial infection, the H. pylori-infected mice were sacrificed.Results : After 80 weeks of infection, almost all the H. pylori-infected mice developed hyperplastic gastritis, but did not show any evidence of gastric adenoma, dysplasia or carcinoma. PCNA positive cells were most abundant after 50 weeks and tended to decrease thereafter up to 80 weeks, whereas apoptosis began to be noted 8 weeks after H. pylori infection, showing 7–8 apoptotic cells/high power field, and tending to increase as time passed. Normally observed neutral mucin decreased during the experiment, showing the most marked decrease 50 weeks after H. pylori infection. In contrast, acidic mucin was noted from 50 weeks after infection.Conclusion : The SS1-infected mouse seems to be a suitable animal model for H. pylori-related research, and H. pylori itself does not induce gastric cancer in normal wild-type mouse model following long-term exposure, which could be explained by the balance that exists between cell proliferation and apoptosis.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    International journal of colorectal disease 14 (1999), S. 101-106 
    ISSN: 1432-1262
    Keywords: Key words Rectal cancer ; Prognosis ; Univariate analysis ; Multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to investigate the changing pattern of rectal cancers in Korea and to identify prognostic factors, we investigated the case histories of 1446 rectal cancer patients who had received surgical treatment. During the study period there were trends toward a decrease in the ratio of rectal cancer to colon cancer, earlier detection (more Dukes' stages A and B and fewer C), a decrease in the number of abdominoperineal resections, and an increase in the number of sphincter-preserving operations. Univariate analysis of prognostic factors showed that gender, obstruction symptoms, preoperative serum carcinoembryonic antigen (CEA) level, tumor size, depth of bowel wall invasion, lymph node metastases (presence and number), tumor differentiation, operative method, and date of operation were significant, but age, symptom duration, and tumor location were not. The use of sphincter-saving operations did not adversely affect the clinical outcome. Multivariate analysis showed lymph node metastasis factor to be the most significant factor (P〈0.001); the depth of bowel wall invasion, differentiation, CEA level, and date of operation were also significant (0.001〈P〈0.05). This study shows that although anatomical extent of disease (depth of invasion and lymph node metastasis) is the most reliable prognostic predictor in rectal cancer, other factors such as preoperative CEA level and tumor differentiation also provide important information on the outcome and use of an anal-preserving operation does not adversely affect the patient survival.
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  • 4
    Publication Date: 2015-11-29
    Description: Several clinical studies have reported increased expression of osteopontin (OPN) in various types of human cancer, including gastric cancer. However, the precise mechanisms underlying tumor development remain unclear. In the present study, we investigated the pathogenic roles of OPN in Helicobacter pylori -induced gastric cancer development. Wild-type (WT) and OPN knockout (KO) mice were treated with N -methyl- N -nitrosourea (MNU) and infected with H.pylori . Mice were killed 50 weeks after treatment, and stomach tissues were assessed by histopathological examination, immunohistochemistry, quantitative real-time RT–PCR and western blotting. To clarify the carcinogenic effects of OPN, we also conducted an in vitro study using AGS human gastric cancer cell line and THP-1 human monocytic cell line. The overall incidence of gastric tumors was significantly decreased in OPN KO mice compared with WT mice. Apoptotic cell death was significantly enhanced in OPN KO mice and was accompanied by upregulation of signal transducer and activator of transcription 1 (STAT1) and inducible nitric oxide synthase (iNOS). In vitro study, OPN suppression also caused STAT1 upregulation and iNOS overexpression in AGS and THP-1 cells, which resulted in apoptosis of AGS cells. In addition, a negative correlation was clearly identified between expression of OPN and iNOS in human gastric cancer tissues. Our data demonstrate that loss of OPN decreases H.pylori -induced gastric carcinogenesis by suppressing proinflammatory immune response and augmenting STAT1 and iNOS-mediated apoptosis of gastric epithelial cells. An important implication of these findings is that OPN actually contributes to the development of gastric cancer.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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