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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 | A draft sequence of the rice (Oryza sativa ssp. indica) genome显示文摘The sequence of the rice genome holds fundamental information for its biology, including physiology, genetics, development, and evolution, as well as information on many beneficial phenotypes of economic significance. Using a 'whole genome shotgun' approach, we have pro-duced a draft rice genome sequence of Oryza sativa ssp. in-dica, the major crop rice subspecies in China and many other regions of Asia. The draft genome sequence is constructed from over 4.3 million successful sequencing traces with an accumulative total length of 2214.9 Mb. The initial assembly of the non-redundant sequences reached 409.76 Mb in length, based on 3.30 million successful sequencing traces with a total length of 1797.4 Mb from an indica variant cultivar 93-11, giving an estimated coverage of 95.29% of the rice genome with an average base accuracy of higher than 99%. The coverage of the draft sequence, the randomness of the sequence distribution, and the consistency of BIG-ASSEM-BLER, a custom-designed software package | YU Jun, HU Songnian, WANG Jun,LI Songgang WONG Ka-Shu Gane, LIU Bin,DENG Yajun, DAI Li, ZHOU Yan,ZHANG Xiuqing, CAO Mengliang, LIU Jing,SUN Jiandong , TANG Jiabin, CHEN Yanjiong,HUANG Xiaobing, LIN Wei, YE Chen, TONG Wei,CONG Lijuan, GENG Jianing, HAN Yujun, LI Lin,LI Wei, HU Guangqiang, HUANG Xiangang,LI Wenjie, LI Jian, LIU Zhanwei, LI Long,LIU Jianping, Ql Qiuhui, LIU Jinsong, LI Li,WANG Xuegang, LU Hong, WU Tingling,ZHU Miao, Nl Peixiang, HAN Hua, DONG Wei,REN Xiaoyu, FENG Xiaoli, GUI Peng,LI Xianran, WANG Hao, XU Xin, ZHAI Wenxue,XU Zhao, ZHANG Jinsong, HE Sijie,ZHANG Jianguo, XU Jichen, ZHANG Kunlin,ZHENG Xianwu, DONG Jianhai, ZENG Wanyong,TAO Lin, CHEN Xuewei, HE Jun, LIU Daofeng,TIAN Wei, TIAN Chaoguang, XIA Hongai,LI Gang, GAO Hui, LI Ping, CHEN Wei ,WANG Xudong, ZHANG Yong, HU Jianfei,WANG Jing, LIU Song, YANG Jian,ZHANG Guangyu, XIONG Yuqing, LI Zhijie,MAO Long, ZHOU Chengshu, ZHU Zhen,CHEN Runsheng, HAO Bailin,ZHENG Weimou, CHEN Shouyi, QUO Wei,LI Guojie, LIU Siqi, HUANG Guyang,TAO Ming, WANG Jian, ZHU Lihuang,YUAN Longping& YANG HuanmingBeijing Genomics Institute/Center of Genomics & Bioinformatics, Chinese Academy of Sciences, Beijing 101300, China Hangzhou Genomics Institute/Institute of Bioinformatics of Zhejiang University/Key Laboratory of Bioinformatics of Zhejiang Province, Hangzhou 310007, China Institute of Genetics, Chinese Academy of Sciences, Beijing 100101, China National Hybrid Rice R & D Center, Changsha 410125, China Laboratory of Bioinformatics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China College of Life Sciences, Peking University, Beijing 100871, China Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 1Q0080, China Digital China Ltd., Beijing 100080, China Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100080, China Medical College, Xi’an Jiaotong University, Xi’an 710061, ChinaThese authors contributed equally to this work.Corresponding author.Corresponden | 2001 | Chinese Science Bulletin2001，46，23： | 6 |
| 3 | Comparison of two anteri- or fusion methods in two-level cervical spondylosis myelopa- thy: a meta-analysis显示文摘 | Huang ZY Wu AM Li QL | 2014 | BMJ Open2014，4，00： | 1 |
| 4 | GM1 improves neurofascin155association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia显示文摘 | Zhang YP Huang QL Zhao CM | 2011 | Braz J Med Biol Res2011，44，6： | 1 |
| 5 | Overproduction, in Escherichia coli, of soluble taxadiene synthase, a key enzyme in the taxol biosynthetic pathway 显示文摘 | Huang KX Huang QL Wildung MR | 1998 | Protein ExprPurif1998，13，1： | 1 |
| 6 | Crystallins and their synthesis in human lens epithelial cells in tissue culture 显示文摘 | Reddy VN Lin LR Arita T Zigler JS Jr Huang QL | 1998 | Exp Eye Res1998，47，3： | 1 |
| 7 | Oriented immobilization of anti-CD34 antibody on titanium surface for self-endothelialization induction显示文摘 | Li QL Huang N Chen C | | 0，，： | 1 |
| 8 | Endothelial injury preceding intracra- nial aneurysm formation in rabbits显示文摘 | Li MH Li PG Huang QL | 2014 | West Indian Med J2014，63，2： | 1 |
| 9 | Comprehensive treatment of malignant lymphomaComprehensive treatment of malignant lymphoma 显示文摘 | Huang YR Gu DZH Wang QL | 1997 | Chin J Radiat Oncol1997，6，2： | 1 |
| 10 | An Albumin-Exendin-4 conjugate engages central and peripheral circuits regulating murine energy and glucose homeostasis显示文摘 | Baggio LL Huang QL Cao XM | 2008 | Gastroenterology2008，134，4： | 1 |
| 11 | Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines显示文摘 | Huang DZ Gao QL Guo LP | 2009 | Stem Cells Dev2009，18，： | 1 |
| 12 | The application of case-based teaching method in clinical teaching of neurosurgery 显示文摘 | LIU HP HUANG QL YANG H | 2011 | Journal of Modern Medicine and Health2011，27，17： | 1 |
| 13 | Comparison of two anteriorfusion methods in two-level cervical spondylosis myelopathy : ameta-analysis显示文摘 | Huang ZY Wu AM Li QL | 2014 | BMJ Open2014，4，7： | 1 |
| 14 | The osteogenetic effect of astragalosideⅣwith centrifugating pressure on the OCT-1 cells显示文摘 | Bian QL Huang JH Liang QQ | 2011 | Die Pharmazie2011，66，1： | 1 |
| 15 | Endothelial cell and platelet behavior on titanium modified with a mutilayer of polyelectrolytes 显示文摘 | LI QL HUANG N CHEN JL | 2009 | J Bioact Compat Pol2009，24，2： | 1 |
| 16 | Preparation, chain conformation and an- ti-tumor activities of water-soluble phosphatcd ( 1-3 ) -(x-D-glcan from Poria cocos mycdia 显示文摘 | Huang QL Zhang LN | 2011 | Carbohydrate Polymers2011，83，3： | 1 |
| 17 | GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia显示文摘 | Zhang YP Huang QL Zhao CM | 2011 | Braz J Med Biol Res2011，44，6： | 1 |
| 18 | LC - APCI - MS - MS for the determination of celastrol in human whole blood 显示文摘 | Q Xu M Huang QL Ren | 2007 | Chromatographia2007，66，910： | 1 |
| 19 | GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia显示文摘 | Zhang YP Huang QL Zhao CM | | 0，，06： | 1 |
| 20 | Development of tertiary hyperparathyroidism after phosphate supplemen- tation in oncogenic osteomalacia 显示文摘 | Huang QL Feig DS Blackstein ME | 2000 | J Endocrinol In- vest2000，23，： | 1 |
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