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( Sung Woo Hong ),( Won Hee Hur ),( Jung Eun Choi ),( Young Ki Lee ),( Seung Kew Yoon ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: Recent studies have described that cancer stem cell plays a key role in radioresistance. The cell surface marker CD133 has been known recently as a cancer stem cell marker expressed in HCC. Recently, ADAM17 was reported to contribute to metastasis. The aim of this study is to investigate the molecular and cellular mechanisms of liver cancer stem cell and ADAM17 in metastasis after irradiation in HCC. Methods: Huh-7CD133+ and Huh-7CD133- sorted cells were exposed to g-irradiation. We investigated the key gene/pathway responsible for metastasis in post-irradiated liver cancer stem cells, CD133+/- cells using cDNA microarray. Metastatic activity was analyzed by cell migration assay. Also the expressions of the MMP-2 and MMP-9 were measured by gelatin zymography. We confirmed ADAM17 gene expression on time dependent by real-time PCR, western blot in sorted cells. ADAM17 is suppressed effectively using ADAM17 lenti virus shRNA in Huh-7 cell line. CD133+/- cells that were suppressed ADAM17 gene expression were analyzed migration activity. Results: After cDNA microarray analysis, eighty nine metastasis related genes were upregulated. Especially we found that the ADAM17 gene was more increased in CD133+ cells than CD133- cells treated with g-irradiation. In addition CD133+ cells from radiation exposure were consistently expressed higher levels of vascular endothelial growth factor by Multiplex cytokine analysis. After irradiation, CD133+ cells migrated more actively, and showed an increased invasion rate compared to CD133- cell. Gelatin zymography showed that MMP-2, -9 expressions are significantly higher in CD133+ cells. Furthermore, shADAM17CD133+ cells reduced migration activity after g-irradiation exposure. Conclusions: These results suggest that CD133+ cells have more metastatic capacity than CD133- cells after treating irradiation. These data further suggest that molecular therapeutic inhibition of cell migration and invasion through ADAM17 suppression may represent a new approach for improving the therapeutic efficacy of radiotherapy for HCC. This work was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0027071).
Aucubin, Catalpol, and GABA Content in Different Organ of Rehmannia glutinosa Cultivars
Sang Hoon Lee(이상훈),Jeong Su Yoon(윤정수),Jae Kwang Kim(김재광),Chun Geon Park(박춘근),Mok Hur(허목),Seong Cheol Koo(구성철),Mei Lan Jin,Woo Moon Lee(이우문),Jae Ki Chang(장재기),Yeon Bok Kim(김연복) 한국약용작물학회 2017 한국약용작물학회 학술대회논문집 Vol.2017 No.1
( Sung Woo Kim ),( Won Hee Hur ),( Kwang Soo Lyoo ),( Jung Eun Choi ),( Sung Woo Hong ),( Young Kee Lee ),( Seung Kew Yoon ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: NAFLD (nonalcoholic fatty liver disease) has a wide spectrum of liver pathogenesis from simple hepatic steatosis to cirrhosis. NASH (Nonalcoholic Steatohepatitis) is characterized by hepatocyte injury and inflammatory cell infiltration, which is linked with peripheral insulin resistance and increased triglyceride in the liver. Pharmacological properties of oleuropein are anti-oxidant, anti-inflammatory, and anti-ageing. The purposes of this study was to establish an NASH mouse model fed with HFD and to demonstrate the pharmacological effect of oleuropein using the appropriative animal model. Methods: C57BL/6 mice were divided into 3 groups; a normal diet group (ND), a 60% high fat diet group (HFD), 0.05% oleuropein-supplemented high fat diet group (HWO). HWO were fed 0.05% oleuropein-supplemented high fat diet after 6 months. The effect of oleuropein on these models was studied using biochemical, histological and molecular markers. Expression of mRNA level (related adipogenesis, inflammation, and fibrosis) was analyzed by real-time PCR between HFD and HWO. Results: The body weight, total cholesterol, TG, FFA, AST, and ALT values of HFD for 6, 9, and 12 months were higher than that of ND. The NAFLD activity score (NAS) of HFD were increased to inflammation stage at 6 month, compared to ND. HWO was significantly increased to NAS and fibrosis grade, but steatosis grade was not changed. The mRNA levels of LXR, TNF-α and collagen was decreased with treatment period in HWO, but ap2 and α-SMA was not changed. Conclusions: We produced a high fat diet induced NASH model that displayed histopathological features of NAFLD to NASH. The therapeutic effect of oleuropein was prevented with progression of NAFLD to NASH. Therefore, it is speculated that oleuropein may be pharmacologically useful to prevent the progression of steatohepatitis and fibrosis and could be a promising agent of medicine for human NASH. This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. (A090282).