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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 | Activation of glycogen synthase kinase-3 induces Alzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture.显示文摘 | Li X Lu F Tian Q Yang Y Wang Q Wang JZ | 2006 | 中国生物学文摘2006，20，9： | 9 |
| 3 | 持续气道正压通气在预防阻塞性睡眠呼吸暂停患者心血管事件中的作用显示文摘阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)导致阵发性低氧血症,夜间交感神经系统激活,血压、氧化应激和炎症指标的升高以及高凝血症。较大的胸内负压波动也会给心脏和大血管施加机械应力。基于人群和睡眠诊所的队列研究显示,OSA与心脑血管事件,特别是脑卒中相关。 | McEvoy RD Antic NA Heeley E Luo Y Ou Q Zhang X Mediano O Chen R Drager LF Liu Z Chen G Du B McArdle N Mukherjee S Tripathi M Billot L Li Q Lorenzi-Filho G Barbe F Redline S Wang J Arima H Neal B White DP Grunstein RR Zhong N Anderson CS 练桂丽 叶鹏 | 2016 | 中华高血压杂志2016，24，11： | 4 |
| 4 | 油炸食品与心血管病风险和全因死亡率的关系:观察性研究的荟萃分析显示文摘研究者进行了一项荟萃分析,包括剂量反应分析,以定量确定油炸食品摄入与普通成年人群心血管病风险和全因死亡率之间的关系。方法:研究者在PubMed、EMBASE和Web of Science上检索2020年4月11日之前的所有文章。应用随机效应模型估计总的相对危险度(relative risks,RR)和95%CI。结果:与最低油炸食品摄入量相比,最高摄入量者主要心血管事件的总RR(95%CI)=1.28(1.15~1.43),n=17,I^(2)=82.0%,其中前瞻性研究:1.24(1.12~1.38),n=13,I^(2)=75.7%. | 刘青(译) 练桂丽(审校) Qin P Zhang M Han M Liu D Luo X Xu L Zeng Y Chen Q Wang T Chen X Zhou Q Li Q Qie R Wu X Li Y Zhang Y Wu Y Hu D Hu F | 2021 | 中华高血压杂志2021，29，2： | 3 |
| 5 | On-line measurement of the straightness of seamless steel pipe using machine vision technique显示文摘 | lU R S LI Y F YU Q | 2001 | Sensor and Actutors A-Physical2001，94，1： | 2 |
| 6 | Brittle elastoplastic damage constitutive model for jointed rockmass and computation concerning bolt-reinforcement显示文摘 | Zhu W Zhang Q Li S Lee C F | 2003 | International Journal of Damage Mechanics2003，12，： | 2 |
| 7 | 甜菜碱对肥育猪生长激素脉冲释放和血清代谢的影响显示文摘用添加含量为0和0.125%甜菜碱的日粮饲喂肥育猪,试验对杂交肥育猪日粮中甜菜碱对猪的生长性能、生长激素(GH)脉冲释放及血清代谢的影响进行研究。每试验组3个重复,每个重复8头猪(4头去势公猪,4头母猪),试验在饲喂后3h内每15min采集一次血液样本,测定生长激素脉冲释放。结果表明:添加甜菜碱组平均日增重增加5.45%(P〈0.05),而平均日采食量和饲料转化率则不受影响。 | Huang Q C Xu Z R Han X Y Li W F | 2007 | 饲料博览(技术版)2007，，7： | 2 |
| 8 | Engrafted bone marrow-derived flk-(1+) mesenchymal stem cells regenerate skin tissue显示文摘 | Deng W Han Q Liao L Li C Ge W Zhao Z You S Deng H Murad F Zhao RC | 2006 | 中国生物学文摘2006，20，5： | 2 |
| 9 | Electrically conductive epoxy resin composites containing polyaniline with different morphologies 显示文摘 | JIA Q M LI J B WANG L F | 2007 | Materials Science and Engineering A2007，448，： | 1 |
| 10 | Film morphology and orientation of N-β-aminoethyl-γ-propyl polysiloxane on cellulose model substrates显示文摘 | AN Q F LI L S LI M T | 2007 | AATCC Review2007，7，5： | 1 |
| 11 | Superior efficacy of a Cremophor-fiee albumin-bound paclitaxel compared with solvent-based paclitaxel in Chinese patients with metastatic breast cancer显示文摘 | GUAN Z Z LI Q L FENG F Y | 2009 | Asian Pac J Clia Oncol2009，5，3： | 1 |
| 12 | Structure and hydrogenation properties of nanocrystalline Mg2Ni prepared by hydriding combustion synthesis and mechanical milling 显示文摘 | LIU X F ZHU Y F LI L Q | 2008 | Journal of Alloys and Compounds2008，455，： | 1 |
| 13 | Alkaline syenites in eastern Cathaysia (South China): Link to Permian-Triassic transtension显示文摘 | Wang Q Li J W Jian P Zhao Z H Xiong X L Bao Z W Xu J F Li C F Ma J L | 2005 | Emth Planet Sci Lett2005，230，34： | 1 |
| 14 | 显示文摘 | Li Y X Hu Y F Peng S Q | 2009 | J Phys Chem C2009，113，： | 1 |
| 15 | A novel titanium-supported Ag/Ti electrode for the electro-oxidation of hydrazine 显示文摘 | Yi Q F Li L Yu W Q | 2008 | Journal of Molecular Catalysis A: Chemical2008，295，： | 1 |
| 16 | Research on iris image preprocessing algo- rithm显示文摘 | Zhang P F Li Q M | 2005 | IEEE Machine Learning and Cybernetics2005，8，： | 1 |
| 17 | Surgical treatment of 40 patients with thoracic ossification of the ligamentum flavum显示文摘 | Li F Chen Q Xu K | 2006 | J Neurosurg Spine2006，4，3： | 1 |
| 18 | Water uptake and acid doping of polybenzimidazoles as electrolyte membranes for fuel cells显示文摘 | LI Q F HE R H BERG R W | 2004 | Solid State Ionics2004，168，12： | 1 |
| 19 | Time-domain modeling of high-speed interconnects by modified method of characteristics显示文摘 | Q Xu Z F Li P Mazumder J F Mao | 2000 | IEEE Trans Microwave Theory and Tech2000，48，2： | 1 |
| 20 | Residual LifePredictions for Ball Bearings Based on Self-organ-izing Map and Back Propagation Neural NetworkMethods显示文摘 | Huang R Q Xi L F Li X L | 2007 | Mechanical Systems and Signal Pro-cessing2007，21，1： | 1 |
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