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류지곤 대한소화기학회 2015 대한소화기학회지 Vol.66 No.3
Pancreatic adenocarcinoma is one of the fatalist malignancies. A large proportion of patients are diagnosed with unresectable stage pancreatic cancer at the time of presentation. Gemcitabine is a standard chemotherapeutic agent since 1997, but survival benefit is not satisfactory. Recent clinical study proved that several new combination chemotherapy regimens are superior to gemcitabine single chemotherapy and extended overall survival. However, its prognosis still remains grim. Current research is taking a multidirectional approach in the hope of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. This article also reviews the current ongoing clinical trials, which include the use of molecular targeting agents and immune therapies.
Clobenpropit Enhances Anti-Tumour Effect of Gemcitabine In Pancreatic Cancer
류지곤 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.2
Background: Histamine is associated with carcinogenesis through activation of its 4 membrane-specific receptors. We evaluated the anti-tumour effect of clobenpropit, which is the specific H3 antagonist and H4 agonist, with gemcitabine combination in pancreatic cancer cell line.Methods: Three kinds of human pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and AsPC-1) were used in this study. Expression of H3 and H4 receptor in pancreatic cancer cell was identified with Western blotting. Effects of clobenpropit on cell proliferation, migration and apoptosis were evaluated. Alteration of epithelial and mesenchymal markers after administration of clobenpropit was analyzed. In vivo study with Panc-1 xenograft mouse model was also performed. Results: H4 receptors were present as 2 subunits in human pancreatic cancer cells, while there was no expression of H3 receptor. Clobenpropit inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine. Clobenpropit up-regulated E-cadherin, whereas down-regulated vimentin and matrix metalloproteinase 9 in real-time PCR. Also, clobenpropit inhibited tumour growth and enhanced apoptosis in combination with gemcitabine by up-regulation of E-cadherin and down-regulation of Zeb1 in Panc-1 xenograft mouse. Conclusion: Clobenpropit enhanced anti-tumour effect of gemcitabine in pancreatic cancer cells through inhibition of epithelial- mesenchymal transition process.