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| 1 | Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3显示文摘AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC).METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model.RESULTS: Sorafenib decreased STAT3 phosphorylationat the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phosphatase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib signifi cantly inhibited STAT3 activity, reducing tumor growth and metastasis.CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation. | Fang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian ZhouFang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian Zhou, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai 200032, China Author contributions: Gu FM, Li QL and Gao Q contributed equally to this work Gu FM and Li QL performed the experi- ments and interpretation of the data and statistical analysis Zhou J and Gao Q contributed to the conception and design of the study Gu FM, Gao Q, Li QL and Zhou J wrote the manuscript Jiang JH, Huang XY, Pan JF and Fan J made substantial contri- bution to the design and conception of the study and interpreta- tion of data all authors read and approved the f inal manuscript. | 2011 | World Journal of Gastroenterology2011，17，34： | 18 |
| 2 | Sedation and safety of propofol for therapeutic endoscopic retrograde cholangiopancreatography显示文摘Endoscopic retrograde cholangiopancrea tography(ERCP) is the most complex gastrointestinal procedure,which needs patients’ cooperation. The aim of this study was to observe the quality and safey of sedation with propofol in patients undergoing therapeutic ERCP. METHODS:Seventy patients who had undergone therapeutic ERCP were randomly divided into two groups.One group, given intravenously propofol, and the other sedated with routine method, served as the control. Blood pressure, heart rate,oxygen saturation were monitored and cardiorespiratory event was observed. Patient cooperation,performance, recovery time and amnesia served as variables postoperation. RESULTS:Blood pressure elevated in four patients in the propofol group, less than in the control group(P<0.01). Seven patients showed decreased blood pressure after administration of propofol,but none in the control group (P<0.01). Twelve patients in the control group showed mild or significant resistance, but none in the propofol group (P<0.01). The time for performance in the propofol group(P<0.05) was shorter than in the control group. Patient recovery was quicker in the propofol group than in the control group (P<0.01). The degree of amnesia better in the propofol group than in the control group ( P<0.01). The degree of amnesia was also better in the propofol group than in the control group (P<0.01). CONCLUSIONS:Propofol proves to be an excellent sedative for therapeutic ERCP. Being effective and safe, it shows a shorter ERCP duration but quick recovery and better amnesia. It is better than other routine sedatives. | Digestive Department (Chen WX, Lin HJ, Gu Q, Zhong XQ, Yu CH, Li YM and Gu ZY) and Department of Intensive Care Unit (Zhang WF), First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003 , China | 2005 | Hepatobiliary & Pancreatic Diseases International2005，4，3： | 10 |
| 3 | Mg-Ca-Zn bulk metallic glasses with high strength and significant ductility显示文摘 | GU X SHIFLET G J GUO F Q POON S J | 2005 | Journal of Materials Research2005，20，8： | 1 |
| 4 | An ANN-based multilevel classification approach using decomposed input space for transient stability assessment显示文摘 | Tso S K Gu X P Zeng Q Y | 1998 | Electric Power Systems Research1998，46，3： | 1 |
| 5 | A short note on quenching phenomena for semilinear parabolic equations 显示文摘 | Dai Q Y Gu Y G | 1997 | J Differential Equations1997，137，： | 1 |
| 6 | 显示文摘 | Gu X Q Zhu L P Cao L | 2011 | Materials Science in Semiconductor Processing2011，14，： | 1 |
| 7 | Age-related autophagy alterations in the brain of senescence accelerated mouse prone 8 (SAMP8) mice显示文摘 | Ma Q Qiang J Gu P | 2011 | Exp Gerontol2011，46，7： | 1 |
| 8 | Quantification of huperzine A in Huperzia serrata by HPLC-UV and identification of the major constituents in its alkaloid extracts by HPLC-DAD-MS-MS 显示文摘 | Wu Q Gu Y | 2006 | J Pharm Biomed Anal2006，40，4： | 1 |
| 9 | A novel flotation column for oily water cleanup 显示文摘 | Gu X Q Chiang S H | 1999 | Separation Purification Technology1999，，16： | 1 |
| 10 | Blood pressure responses to dietary sodium and potassium interventions and the cold pressor test: the gen salt replication study in rural north China 显示文摘 | Zhao Q Gu D Chen J | 2014 | Am J Hyper- tens2014，27，1： | 1 |
| 11 | The impact of online user reviews on hotel room sales 显示文摘 | Ye Q Law R Gu B | 2009 | International Journal of Hospitality Management2009，28，1： | 1 |
| 12 | Determination of amputation level in ischaemic lower limbs 显示文摘 | Gu Y Q | 2004 | AN Z J Surg2004，74，12： | 1 |
| 13 | c-Jun N-terminal kinase activation in hippocampal CA1 region was involved in ischemic injury 显示文摘 | Gu Z Jiang Q Zhang G | 2001 | Neuroreport2001，12，5： | 1 |
| 14 | Nitrogen transfer of fuel-N in chemical looping combustion 显示文摘 | Song T Shen L H Xiao J Chen D Q Gu H M Zhang S W | 2012 | Combustion and Flame2012，159，3： | 1 |
| 15 | Performance and Risk Assessment of Soil-Sructure In- teraction Systems Based on Finite Element Reliability Methods 显示文摘 | Gu Q | 2014 | Mathematical Problems in Engineering2014，，2： | 1 |
| 16 | Effects of Carbon Black on the Properties of HNBR Reinforced by in-situ Prepared ZDMA显示文摘 | Zhao X B Zhang Q Y Gu J W | 2011 | Polymer Plastics Technology and Engineering2011，50，15： | 1 |
| 17 | Kinetics and mechanism for oxi- dative desulfurization of fuels catalyzed by peroxo-molybdenum ami- no acid complexes in water-immiscible ionic liquids 显示文摘 | ZHU W S LI H M GU Q Q | 2011 | J Mol Catal A Chem2011，336，12： | 1 |
| 18 | Continuous deposition of buffer layers for YBCO coated conductor using reactive magnetron sputtering 显示文摘 | Yang J Liu H Z Qu F Zhang H Zhou Q Gu H W | 2007 | Materials Science Forum2007，54，6549： | 1 |
| 19 | Mortality trends in men and women with diabetes, 1971 to 2000 显示文摘 | Gregg EW Gu Q Cheng YJ | 2007 | Ann Intern Med2007，147，3： | 1 |
| 20 | Unexpected C02 splitting reactions to form CO with N-heterocyclic carbenes as organocatalysts and aromatic aldehydes as oxygen acceptors显示文摘 | Gu L Q Zhang Y G | 2010 | J Am Chem Soc2010，132，3： | 1 |
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