These results clearly demonstrated the role of H. pylori infection, rather than direct carcinogens, in promoting gastric carcinogenesis in a mice model.
Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (55% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (525% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and Pglycoprotein expression (P50.0001) as well as P-glycoprotein and thymidylate synthase expression (P50.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P50.0001 and P=0.03, respectively) and intestinal type (P50.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), Pglycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistanceassociated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicinbased adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary.
SUMMARYBackground: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immunoinflammatory response in gastric mucosa imposed by Helicobacter pylori. Aim: To determine the implications of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment. Methods: C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL-1b, TNF-a, IFN-c and IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-jB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group
SUMMARYBackground: 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 ¼ 115) were infected with SS1, the mouseadapted 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,
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