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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 | Solving surface plasmon resonances and near field in metallic nanostructures:Green’s matrix method and its applications显示文摘With the development of nanotechnology,many new optical phenomena in nanoscale have been demonstrated.Through the coupling of optical waves and collective oscillations of free electrons in metallic nanostructures,surface plasmon polaritons can be excited accompanying a strong near field enhancement that decays in a subwavelength scale,which have potential applications in the surface-enhanced Raman scattering,biosensor,optical communication,solar cells,and nonlinear optical frequency mixing.In the present article,we review the Green's matrix method for solving the surface plasmon resonances and near field in arbitrarily shaped nanostructures and in binary metallic nanostructures.Using this method,we design the plasmonic nanostructures whose resonances are tunable from the visible to near-infrared,study the interplay of plasmon resonances,and propose a new way to control plasmonic resonances in binary metallic nanostructures. | GU Ying LI Jia MARTIN Olivier J F GONG QiHuang | 2010 | Chinese Science Bulletin2010，55，24： | 3 |
| 3 | Distribution of time between failures of machining center based on type Ⅰ censored data显示文摘 | Dai Y Zhou Y F Jia Y Z | 2003 | Reliability Engineering and System Safety2003，79，3： | 1 |
| 4 | 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 |
| 5 | Sliding wear behavior of copper alloy contact wire against copper-based strip for high-speed electrified railways 显示文摘 | Jia S G Liu P Ren F Z | 2007 | Wear2007，262，78： | 1 |
| 6 | A peptide targeted contrast specific to Fibrin-Fibronectin complexes for cancer molecular imaging with MRI显示文摘 | Ye F Jeong EK Jia Z | 2008 | Bioconjugate Chem2008，19，： | 1 |
| 7 | Mechanism of gold and silver species on activated carbon显示文摘 | Jia Y F Steele J Hayward P | 1998 | Carbon1998，36，9： | 1 |
| 8 | Synthesis and antibacterial activities of quaternary ammonium salt of chitosan显示文摘 | Jia Z S Shen D F Xu W L | 2001 | Carbohydrate Res2001，333，1： | 1 |
| 9 | Pharmacokinetic properties of hydroxysafflor yellow A in healthy Chinese female volunteers显示文摘 | Yang Z F Yang J Jia Y Y | 2009 | J Ethnopharmacol2009，124，3： | 1 |
| 10 | A 100 kW high-per- formance PWM rectifier with a ZCT soft-switching tech- nique显示文摘 | Jia W Lee F C Boroyevich D | 2003 | IEEE Transactions on Power Electronics2003，18，6： | 1 |
| 11 | New constructions of bal- anced Boolean functions with high nonlinearity and optimal algebraic degree 显示文摘 | ZHANG F R HU Y P JIA Y Y | 2012 | International Journal of Computer Mathematics2012，89，10： | 1 |
| 12 | Entanglement and non- classicality of photon-added two-mode squeezed thermal state 显示文摘 | HU L Y JIA F ZHANG Z M | 2012 | J Opt Soc Am B2012，29，6： | 1 |
| 13 | The structure and electronic property of BN nanotube 显示文摘 | Jia J F Wu H S Jiao H J | 2006 | Physica B2006，381，： | 1 |
| 14 | Oxidative stress, antioxidant status and DNA damage in patients with impaired glucose regulation and newly diagnosed type 2 diabetes显示文摘 | Song F Jia W Yao Y | 2007 | Clin Sci (Lond)2007，112，12： | 1 |
| 15 | Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose显示文摘 | Jia D Y Liu H J Wang F W | 2008 | Neurosci Lett2008，440，1： | 1 |
| 16 | Predictors of HIV infection and prevalence for syphilis infection among injection drug users in China: Community-based surveys along major drug trafficking routes 显示文摘 | Jia YJ Lu F Zeng G | 2008 | Harm Reduct J2008，5，： | 1 |
| 17 | Estimating N Status of Winter Wheat Using a Handheld Spectrometer in the North China Plain 显示文摘 | Li F Gnyp M L Jia L L | 2008 | Field Crops Research2008，106，1： | 1 |
| 18 | Breast cancer resistance protein-media- ted topotecan resistance in ovarian cancer cells 显示文摘 | Jia P Wu S Li F | 2005 | Int J Gynecol Cancer2005，15，6： | 1 |
| 19 | Interleukin(IL)-12 and IL-12 gene transfer up-regulate Fas expression in human osteosarcoma and breast cancer cells显示文摘 | Lafleur E A Jia S F Worth L L | 2001 | Cancer Res2001，61，10： | 1 |
| 20 | Visual acuity and quality of life outcomes in patients with cataract in Shuyi county,China显示文摘 | Zhao J L Sui R F Jia L J | 1998 | Am J Ophthalmol1998，126，： | 1 |
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