AIM： To evaluate the optimal intervention point of a selective cyclooxygenase-2 （COX-2） inhibitor, Celecoxib, for inhibiting Helicobacter pylori （H pylori-associated gastric carcinogenesis in Mongolian gerbils （...AIM： To evaluate the optimal intervention point of a selective cyclooxygenase-2 （COX-2） inhibitor, Celecoxib, for inhibiting Helicobacter pylori （H pylori-associated gastric carcinogenesis in Mongolian gerbils （MGs）.METHODS： One hundred and twelve MGs were divided into six groups （A-F）. One hundred gerbils were inoculated with H pylor/（groups A-E）. Twelve gerbils were inoculated with vehicle broth only （group F）. After 4 wk, they were given N＇-methyl-N＇ -nitro-N-nitroso-guanidine （MNNG） （50 μg/mL） in the drinking water for 20 wk. in groups B-E, the animals were given the stock Celecoxib （10 mg/kg per day） diet from the 21st, 31st, 21st and 41st week respectively. The periods of administering Celecoxib were 30, 20, 20, and 15 wk respectively. On the 51st week, the animals were sacrificed for histological examination. Local PCNA expression was examined by the immunohistochemistry method. The expression of COX-2 protein was assessed by Western Blot. Analysis used the 2 test. The difference was regarded as significant when P value was less than 0.05. RESULTS： Seventeen percent （17/100） of H pyloriinfected MGs developed gastric cancer. All of these lesions were well-differentiated adenocarcinoma. The incidence rates of adenocarcinoma in groups A-F were 40%, 0%, 0%, 20%, 25%, and 0% respectively. The inflammatory scores were higher in group B than in other groups. There was no inflammatory response noted in group F. Celecoxib treatment resulted in a significant reduction in the proliferation of H pyloriinfected mucosal cells （groups B, C and D） （P 〈 0.01）. The expression of COX-2 protein was significantly attenuated in the groups which were Celecoxib-treated for more than 20 wk （groups B, C, D）. The groups treated with Celecoxib had a significantly lower rate of advanced gastric cancer （34% vs 75%, P 〈 0.001） There were no sudden deaths in any of the groups. CONCLUSION： Short-term treatment with Celecoxib has an anti-carcinogenic effect, and resulted in less severe inflammation and inhibited the invasive degree of gastric cancer.展开更多
A few signaling pathways are driving the growth of hepatocellular carcinoma.Each of these pathways possesses negative regulators.These enzymes,which normally suppress unchecked cell proliferation,are circumvented in t...A few signaling pathways are driving the growth of hepatocellular carcinoma.Each of these pathways possesses negative regulators.These enzymes,which normally suppress unchecked cell proliferation,are circumvented in the oncogenic process,either the overactivity of oncogenes is sufficient to annihilate the activity of tumor suppressors or tumor suppressors have been rendered ineffective.The loss of several key tumor suppressors has been described in hepatocellular carcinoma.Here,we systematically review the evidence implicating tumor suppressors in the development of hepatocellular carcinoma.展开更多
基金Supported by A grant from Kaohsiung Medical University (Q096014)Kaohsiung Municipal Hsiao-Kang Hospital (kmhk-96-005, kmhk-95-005)
文摘AIM： To evaluate the optimal intervention point of a selective cyclooxygenase-2 （COX-2） inhibitor, Celecoxib, for inhibiting Helicobacter pylori （H pylori-associated gastric carcinogenesis in Mongolian gerbils （MGs）.METHODS： One hundred and twelve MGs were divided into six groups （A-F）. One hundred gerbils were inoculated with H pylor/（groups A-E）. Twelve gerbils were inoculated with vehicle broth only （group F）. After 4 wk, they were given N＇-methyl-N＇ -nitro-N-nitroso-guanidine （MNNG） （50 μg/mL） in the drinking water for 20 wk. in groups B-E, the animals were given the stock Celecoxib （10 mg/kg per day） diet from the 21st, 31st, 21st and 41st week respectively. The periods of administering Celecoxib were 30, 20, 20, and 15 wk respectively. On the 51st week, the animals were sacrificed for histological examination. Local PCNA expression was examined by the immunohistochemistry method. The expression of COX-2 protein was assessed by Western Blot. Analysis used the 2 test. The difference was regarded as significant when P value was less than 0.05. RESULTS： Seventeen percent （17/100） of H pyloriinfected MGs developed gastric cancer. All of these lesions were well-differentiated adenocarcinoma. The incidence rates of adenocarcinoma in groups A-F were 40%, 0%, 0%, 20%, 25%, and 0% respectively. The inflammatory scores were higher in group B than in other groups. There was no inflammatory response noted in group F. Celecoxib treatment resulted in a significant reduction in the proliferation of H pyloriinfected mucosal cells （groups B, C and D） （P 〈 0.01）. The expression of COX-2 protein was significantly attenuated in the groups which were Celecoxib-treated for more than 20 wk （groups B, C, D）. The groups treated with Celecoxib had a significantly lower rate of advanced gastric cancer （34% vs 75%, P 〈 0.001） There were no sudden deaths in any of the groups. CONCLUSION： Short-term treatment with Celecoxib has an anti-carcinogenic effect, and resulted in less severe inflammation and inhibited the invasive degree of gastric cancer.
基金The Stiftung für die Leberkranheiten,the EASLfellowship to JM and the Swiss National Foundation grant#3100-063696 to JFD
文摘A few signaling pathways are driving the growth of hepatocellular carcinoma.Each of these pathways possesses negative regulators.These enzymes,which normally suppress unchecked cell proliferation,are circumvented in the oncogenic process,either the overactivity of oncogenes is sufficient to annihilate the activity of tumor suppressors or tumor suppressors have been rendered ineffective.The loss of several key tumor suppressors has been described in hepatocellular carcinoma.Here,we systematically review the evidence implicating tumor suppressors in the development of hepatocellular carcinoma.
