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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 | Nitrite-derived nitric oxide by xanthine oxidoreductase protects the liver against ischemia- reperfusion injury显示文摘It was demonstrated that xanthine oxidoreductase (XOR), during ischemia, catalyzes the formation of nitric oxide (NO) from nitrite (NO2-) and this NO2--derived NO protects the isolated perfused rat heart against the damaging effects of ischemia-reperfusion (I/R) when conventional nitric oxide synthase (NOS) -dependent NO production is impaired. Liver is one of the organs with the highest XOR concentration. This study was designed to determine whether NO2--derived NO by XOR protects liver against I/R injury in vivo. For its minute amounts and active reactivity, NO can not be detected directly in real time in vivo by this time. We have to prove the above hypothesis indirectly. METHODS:Wistar rats were pretreated with saline, NOS inhibitor L-NAME (10 mg/kg intravenously), XOR inhibitor allopurinol (1.5 mg/kg orally), L-NAME +allopurinol and NO scavenger carboxy-PTIO (0.6 mg/kg intravenously) respectively (12 animals per group). And then, they were subjected to total liver ischemia for 40 minutes followed by reperfusion. Blood samples and liver tissues were obtained for analysis after 3 hours of reperfusion. Survival was also investigated. RESULTS:Allopurinol-treated animals exhibited further increased serum alanine aminotransferase (ALT) levels and liver myeloperoxidase (MPO) activities, but further decreased liver adenosine triphosphate (ATP) stores after I/R compared to saline-treated counterparts (830.5±108.3 U/L, 56.5±11.0 U/mg protein and 1.93±0.47 μmol/g vs. 505.8± 184.2 U/L, 41.5±10.2 U/mg protein and 3.05±0.55 μmol/g respectively, P<0.01, P<0.05 and P<0.01 respectively). The hepatocyte injury was further exacerbated and the overall survival rate was significantly decreased after I/R in animals given by allopurinol compared to those pretreated by saline (P<0.05). L-NAME and allopurinol co-treated animals exhibited more severe liver injury (P<0.05 and P<0.01) and a further decreased overall survival rate (P<0.05) compared to L-NAME or allopurinol alone-treated counterparts, but they were not different from carboxy-PTIO treated animals (P>0.05). CONCLUSION:NO2--derived NO by XOR in the hypoxic and acidic environment induced by hepatic I/R protects the liver against I/R injury in vivo. | Department of General Surgery ( Lu P, Wang CY and Chen DD), and Department of Radiology (Liu F), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Cold Spring Harbor Laboratory, New York 11724, USA ( Yao Z) General Surgery Laboratory, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology, Wuhan 430022 , China (Tian Y, Zhang JH and Wu YH) | 2005 | Hepatobiliary & Pancreatic Diseases International2005，4，3： | 4 |
| 3 | Interleukin-10 gene polymorphisms and hepatocellular carcinoma susceptibility:A meta-analysis显示文摘AIM: To assess the association between Interleu-kin-10 (IL-10) gene IL-10-1082 (G/A), IL-10-592(C/A), IL-10-819 (T/C) polymorphisms and hepatocellular carcinoma (HCC) susceptibility.METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% conf idence intervals (95% CIs) for IL-10 polymorphisms and HCC were cal-culated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. RESULTS: This meta analysis included seven eligiblestudies, which included 1012 HCC cases and 2308 controls. Overall, IL-10-1082 G/A polymorphism was not associated with the risk of HCC (AA vs AG + GG, OR = 1.11, 95% CI = 0.90-1.37). When stratifying for ethnicity, the results were similar (Asian, OR = 1.12, 95% CI = 0.87-1.44; non-Asian, OR = 1.10, 95% CI = 0.75-1.60). In the overall analysis, the IL-10 polymorphism at position -592 (C/A) was identified as a genetic risk factor for HCC among Asians; patients carrying the IL-10-592*C allele had an increased risk of HCC (OR = 1.29, 95% CI = 1.12-1.49). No association was observed between the IL-10-819 T/C polymorphism and HCC susceptibility (TT vs TC + CC, OR = 1.02, 95% CI = 0.79-1.32).CONCLUSION: This meta-analysis suggests that IL-10-592 A/C polymorphism may be associated with HCC among Asians. IL-10-1082 G/A and IL-10-819 T/C polymorphisms were not detected to be related to the risk for HCC. | Yong-Gang Wei, Fei Liu, Bo Li, Xi Chen, Yu Ma, Lv-Nan Yan, Tian-Fu Wen, Ming-Qing Xu, Wen-Tao Wang, Jia-Yin YangYong-Gang Wei, Fei Liu, Bo Li, Xi Chen, Yu Ma, Lv-Nan Yan, Tian-Fu Wen, Ming-Qing Xu, Wen-Tao Wang, Jia-Yin Yang, Department of Liver and Vascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Prov- ince, China Author contributions: Wei YG and Liu F designed the study, collected and analyzed the data and wrote the manuscript Li B collected and analyzed the data and wrote the manuscript Chen X and Ma Y collected and analyzed the data Yan LN analyzed the data and contributed to the discussion Wen TF and Xu MQ revised the manuscript Wang WT and Yang JY contributed to the discussion Wei YG and Liu F contributed equally to this work. | 2011 | World Journal of Gastroenterology2011，17，34： | 3 |
| 4 | Quality control measures for lowering the seroconversion rate of hemodialysis patients with hepatitis B or C virus显示文摘BACKGROUND: Hemodialysis (HD) patients are at high risk of infection by hepatitis B virus (HBV) or hepatitis C virus (HCV). The present study was designed to determine the impact of quality control measures on the prevention of transmission of blood-borne viruses. METHODS: A total of 6182 adult maintenance HD patients from all HD units in Zhejiang Province were recruited on January 1, 2007. The baseline demographic and clinical characteristics were recorded and all patients were followed up until death or survival at 4 years later. The Quality Control Standards of Hemodialysis were gradually implemented in HD units. The HBV or HCV seroconversion rates of the recruited patients were calculated and compared every year during the observation period. RESULTS: The prevalence of HBV was 8.3% at the beginning of the study, and 6.6% for HCV. With the implementation of the HD quality control measures, the HBV seroconversion rate tended to decrease year by year (χ 2 =6.620, P=0.085), and the HCV seroconversion rate decreased significantly (χ 2 =10.41, P=0.015). Compared with the data in 2007, the HBV seroconversion rate (χ 2 =4.204, P=0.040, relative risk ratio 0.393, 95% CI 0.156-0.991) and the HCV seroconversion rate (χ 2 =7.373, P=0.007, relative risk ratio 0.386, 95% CI 0.189-0.787) decreased significantly in 2010. CONCLUSION: Quality control measures for HD decreased the seroconversion rates of HBV or HCV in HD patients, showing that updated quality control measures reduce the risk for transmission of blood-borne viruses in the HD population. | Jing Yuan,Yi Yang, Fei Han, Ping Zhang, Xiao-Ying Du, Hua Jiang and Jiang-Hua Chen The Kidney Disease Center, First Affiliated Hospital, Zhejiang University School of Medicine (Yuan J, Yang Y, Han F, Zhang P, Du XY, Jiang H and Chen JH) and Hemodialysis Quality Control Center of Zhejiang Province (Yuan J, Zhang P, Du XY and Chen JH), Hangzhou 310003, China | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，3： | 2 |
| 5 | Using markers in gene introgression breeding programs 显示文摘 | HOSPITAL F CHEVALET C MULSANT P | 1992 | Ge- netics1992，132，： | 1 |
| 6 | Marker-assisted selection efficiency in populations of finite size显示文摘 | Moreau L Charcosset A Hospital F | 1992 | J Dairy Sci1992，，75： | 1 |
| 7 | The use of molecular genetics in the improvement of agricultural populations显示文摘 | Dekkers J C Hospital F | | 0，，01： | 1 |
| 8 | Marker-assisted selection efficiency in populations of finite size显示文摘 | MOREAU L CHARCOSSET A HOSPITAL F | 1998 | Genetics1998，148，： | 1 |
| 9 | Marker-assisted selection efficiency in populations of finite size 显示文摘 | Moreau L Charcosset A Hospital F | 1992 | J Dairy Sci1992，，75： | 1 |
| 10 | Technological implications of reducing nitrate and nitrite levels indry-fermented sausages:Typical microbiota,residual nitrate and nitrite and volatile profile显示文摘 | HOSPITAL X F CARBALLO J FERNNDEZ M | 2015 | Food Control2015，57，： | 1 |
| 11 | Marker assisted selection efficiency in populations of finitesize显示文摘 | Moreau L Charcosset A Hospital F | | 0，，： | 1 |
| 12 | More on the efficiency of marker-as sisted selection显示文摘 | Hospital F Moreau L Lacoudre F | | 0，，： | 1 |
| 13 | The ECCO study显示文摘 | Almagro P López Garcí a F Cabrera F et aL Comorbidity and gender-related differences in patients hospitalized for COPD | 2010 | Respiratory Medicine2010，104，： | 1 |
| 14 | Using markers in gene introgression breeding programs 显示文摘 | Hospital F Chevalet C Mulsant P | 1992 | Genetics1992，132，4： | 1 |
| 15 | Marker-assisted selection efficiency in populatons of finite size显示文摘 | Charcosse A Hospital F | 1998 | Genetics1998，148，： | 1 |
| 16 | The use of molecular genetics in the improvement of agricultural populations 显示文摘 | Dekkers J C M Hospital F | 2002 | Nature Reviews Genetics2002，3，1： | 1 |
| 17 | Marker - assisted introgression of quantitative trait loci 显示文摘 | Hospital F Charcosset A | 1997 | Genetics1997，147，： | 1 |
| 18 | The use of molecular genetics in improvement of agricultural populations显示文摘 | DEKKERS J C M HOSPITAL F | 2002 | Nat Rev Genet2002，3，： | 1 |
| 19 | Using markers in gene introgression breeding programs显示文摘 | Hospital F Chevalet C Mulsant P | 1992 | Genetics1992，132，： | 1 |
| 20 | Marker-assisted selection efficiency in populations of finite size 显示文摘 | Moreau L Charcosset A Hospital F | 1992 | Dairy Sei1992，75，： | 1 |
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