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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 | Portal vein embolization by fine needle ethanol injection :experimental and clinicalstudies显示文摘AIM To improve the technique of intraportal embolization (PVE) therapy, a new embolic method, was devised and the safety, effectiveness and feasibility were evaluated. METHODS PVE with intraportal ethanol injection via a fine needle was performed in 28 normal dogs, 22 SD rats, and 24 cirrhotic SD rats. After PVE, portography, histological and functional alteration of the liver were evaluated in dogs and rats, and the changes in portal hemodynamics as well as hepatic anatomy were observed in rats. In the clinical study, PVE by ethanol injection was performed in 61 patients with hepatocellular carcinoma under the guidance of portoechography with intraportal injection of CO 2. The effect of PVE was evaluated by ultrasonography and laparotomy. RESULTS The effectiveness and toxicity were dependent on the dose of ethanol. In the dogs, 0 25*!mg/*!kg of ethanol caused incomplete embolization with least liver damage, while 1 0*!mg/*!kg induced complete embolization with a high mortality of 57 1% (4/*!7) due to respiratory arrest. The dose of 0 5*!mg/*!kg resulted in complete embolization with slight toxicity to the liver. In the rats, the survival rate was 100% in normal group but 40 9% in cirrhotic models after ethanol injection by dose of 0 05*!mg/*!100*!g . PVE for cirrhotic rats with 0 03*!mg/*!100*!g of ethanol induced satisfactory embolization with significant hypertrophy in nonembolized lobes, and only slight damage to the hepatic parenchyma, and transient alteration in liver function, portal pressure and portal flow. In the clinical study, 12 cases with reverse portal flow were excluded judged by portoechography. Satisfactory embolization was gained in 90 2% (55/*!61) of the remaining patients determined by ultrasonography and surgery. All cases ran an uneventful postembolization course with no aberrant embolization. CONCLUSION PVE with intraportal ethanol injection of appropriate dosage via a fine needle is safe and effective and has several advantages comparing with transcatheter method. Portoechography is a mandatory approach for the prevention of aberrant embolization. | Lu MD Chen JW Xie XY Liang LJ Huang JF | 1999 | World Journal of Gastroenterology1999，5，6： | 15 |
| 3 | Orthotopic liver transplantation for fulminant hepatitis B显示文摘INTRODUCTION When fulminant hepatitis progress to deep encephalopathy,with stage Ⅲ or Ⅳ coma,it is commonly irreversible with a high mortality rate(80%-100%).Liver transplantation may be | He XS Huang JF Chen GH Fu Q Zhu XF Lu MQ Wang GD Guan XD | 2000 | World Journal of Gastroenterology2000，6，3： | 14 |
| 4 | Overexpression of P-glycoprotein in hepatocellular carcinoma and its clinical implication显示文摘INTRODUCTIONMost advanced hepatocellular garcinoma (HCC) isinsensitive to most anticancer drugs which might berelated to the high frequency of expression of themultidrug resistance-1(MDR1) gene and itsproduct,P-glycoprotein (p-gp).p-gp expressionmay also be concerned with tumor progression anddifferentiation.In the present study。 | Kong XB Yang ZK Liang LJ Huang JF Lin HL | 2000 | World Journal of Gastroenterology2000，6，1： | 13 |
| 5 | Partitioning regularity of nonionic organic mixtures in organic phase/water system显示文摘The partitioning regularity of nonionic organic mixtures in organic phase/water system is revealed. The equation for calculating the partition coefficients of mixtures (KMD), together with the determination model, is derived from the equilibrium partitioning models (EPMs). Based on these derived equations, the KMD values of 20 mixtures containing halogenated benzenes are obtained. The results show that stronger hydrophobidty of an individual chemical in the mixture results in the stronger hydrophobidty of the mixture and the greater the proportion of this chemical, the stronger the hydrophobidty of the mixture will be. This partitioning regularity is helpful to the study of the toxicity for mixtures and the environmental behavior, such as transfer or accumulation, for mixed organic pollutants. | Lin, ZF Yu, HX Huang, LM Feng, JF Wang, LS | 2001 | Chinese Science Bulletin2001，46，17： | 2 |
| 6 | T Insulin independence following isolated islet transplantation and single islet infusions 显示文摘 | Markmarm JF Deng S Huang X | 2003 | Ann Surg2003，237，6： | 1 |
| 7 | Color Doppler velocity profile assessment of portal hemodynamics in cirrhotic patients with portal hypertension:correlation with esophageal variceal bleeding显示文摘 | Yin XY Lu MD Huang JF | | 0，，01： | 1 |
| 8 | Heart rate influence on incidence of cardiovascular disease among adults in China 显示文摘 | Mao Q Huang JF Lu X Chen J | 2010 | Int J Epidemiol2010，39，6： | 1 |
| 9 | The effects of electrically assisted methods on transdermal delivery of nalbuphine benzoate and sebacoyl dinalbuphine ester from solutions and hydrogels 显示文摘 | Huang JF Sung KC Hu OYP | 2005 | Int J Pharm2005，297，12： | 1 |
| 10 | HBx - related lncRNA Dreh inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin显示文摘 | Huang JF Guo YJ Zhao CX | 2013 | Hepatology2013，57，5： | 1 |
| 11 | Color Doppler velocity pmfile assessment of portal hemodymamics in cirrhotic patients with portal hypertension : Correlation with esophageal variceal bleeding显示文摘 | Yin XY Lu MD Huang JF | 2001 | J Clin Ultrasound2001，29，1： | 1 |
| 12 | Surgical treatment of hilar stricture hepatolithiasis显示文摘 | Huang JF Qian W | 1997 | Hepatogastroenterology1997，44，3： | 1 |
| 13 | Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1显示文摘 | Huang XZ Wu JF Ferrando R | 2000 | Mol Cell Biol2000，20，14： | 1 |
| 14 | Inhibition of Per-Abl kinaseactivity by PD180970 blocks constitutive activation of Stat5 and growth of CMI ceils显示文摘 | Huang M Dorsey JF Epling-Burnette PK | 2002 | Oncogene2002，21，57： | 1 |
| 15 | Immunohistochemicalevidence for macroautophagy in neurones and endothelial cells inAlzheimer’s disease 显示文摘 | Ma JF Huang Y Chen SD | 2010 | Neuropathol Appl Neurobiol2010，36，4： | 1 |
| 16 | Establishment and characterization of human metastatic hepatocellular carcinoma cell line显示文摘 | Wen JM Huang JF Hu L | 2002 | Cancer Genet Cytogenet2002，135，1： | 1 |
| 17 | Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects显示文摘 | Huang ZP Chen JF Regan JN | 2010 | Arterioscler Thromb Vasc Biol2010，30，12： | 1 |
| 18 | Heart rate influence on incidence of cardiovascular disease among adults in China显示文摘 | Mao Q Huang JF Lu X | 2010 | Int J EPid- emiology2010，39，6： | 1 |
| 19 | Rapid virological responseand treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial 显示文摘 | YuML Dai CY Huang JF | 2008 | Hepatology2008，47，6： | 1 |
| 20 | Optimal investment under stochastic interest rates: the case of a protected defined contribution pension fund 显示文摘 | Boulier JF Huang S Taillard G | 2001 | Insurance: Mathematics and Economics2001，28，： | 1 |
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