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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 | Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach显示文摘AIM: To explore the impact of tumor size on outcomes in patients with advanced gastric cancer in the lower third of the stomach. METHODS: We retrospectively analyzed the clinical records of 430 patients with advanced gastric cancer in the lower third of the stomach who underwent distal subtotal gastrectomy and D2 lymphadenectomy in our hospital from January 1998 to June 2004. Receiver-operating characteristic (ROC) curve analysis was used to determine the appropriate cutoff value for tumor size, which was measured as maximum tumor diameter. Based on this cutoff value, patients were divided into two groups: those with large-sized tumors (LSTs) and those with small-sized tumors (SSTs). The correlations between other clinicopathologic factors and tumor size were investigated, and the 5-year overall survival (OS) rate was compared between the two groups. Potential prognostic factors were evaluated by univariate KaplanMeier survival analysis and multivariate Cox's propor-tional hazard model analysis. The 5-year OS rates in the two groups were compared according to pT stage and pN stage. RESULTS: The 5-year OS rate in the 430 patients with advanced gastric cancer in the lower third of the stomach was 53.7%. The mean ± SD tumor size was 4.9 ± 1.9 cm, and the median tumor size was 5.0 cm. ROC analysis indicated that the sensitivity and specificity results for the appropriate tumor size cutoff value of 4.8 cm were 80.0% and 68.2%, respectively (AUC=0.795, 95%CI: 0.751-0.839, P=0.000). Using this cutoff value, 222 patients (51.6%) had LSTs (tumor size ≥ 4.8 cm) and 208 (48.4%) had SSTs (tumor size<4.8 cm). Tumor size was significantly correlated with histological type (P=0.039), Borrmann type (P=0.000), depth of tumor invasion (P=0.000), lymph node metastasis (P=0.000), tumor-nodes metastasis stage (P=0.000), mean number of metastatic lymph nodes (P=0.000) and metastatic lymph node ratio (P=0.000). Patients with LSTs had a significantly lower 5-year OS rate than those with SSTs (37.1% vs 63.3%, P=0.000). Univariate analysis showed that depth of tumor invasion (c 2=69.581, P=0.000), lymph node metastasis (c 2=138.815, P=0.000), tumor size (c 2=78.184, P=0.000) and metastatic lymph node ratio (c 2=139.034, P=0.000) were significantly associated with 5-year OS rate. Multivariate analysis revealed that depth of tumor invasion (P=0.000), lymph node metastasis (P=0.019) and tumor size (P=0.000) were independent prognostic factors. Gastric cancers were divided into 12 subgroups: pT2N0; pT2N1; pT2N2; pT2N3; pT3N0; pT3N1; pT3N2; pT3N3; pT4aN0; pT4aN1; pT4aN2; and pT4aN3. In patients with pT2-3N3 stage tumors and patients with pT4a stage tumors, 5-year OS rates were significantly lower for LSTs than for SSTs (P<0.05 each), but there were no significant differences in the 5-year OS rates in LST and SST patients with pT23N0-2 stage tumors (P > 0.05). CONCLUSION: Using a tumor size cutoff value of 4.8cm, tumor size is a prognostic factor in patients with pN3 stage or pT4a stage advanced gastric cancer located in the lower third of the stomach. | Hong-Mei Wang, Chang-Ming Huang, Chao-Hui Zheng, Ping Li, Jian-Wei Xie, Jia-Bin Wang, Jian-Xian Lin, Jun Lu, Department of Gastric Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China Author contributions: Wang HM and Huang CM conceived of the study, analyzed the data, and drafted the manuscript Zheng CH, Li P and Xie JW helped revise the manuscript critically for important intellectual content Wang JB, Lin JX and Lu J helped collect data and design the study and all authors read and approved the final manuscript. | 2012 | World Journal of Gastroenterology2012，18，38： | 15 |
| 3 | 澳大利亚人乳头状瘤病毒疫苗计划实施5年对年轻人群生殖器疣患病情况的影响:国家调查数据分析显示文摘目的评估2007年中开始的澳大利亚人乳头状瘤病毒(HPV)疫苗计划对生殖器疣患病情况的影响。设计国家调查数据趋势分析。数据来源数据收集于2004--2011年度澳大利亚8所性健康服务机构;其中2所最大的临床中心收集了自我报告的本中心2009年度HPV疫苗现状。研究对象2004--2011年度首次就诊的85770名澳大利亚出生的国民;其中7686(9.0%)名患生殖器疣。主要结局测量比较前疫苗时期(2004—2007年中)和疫苗时期(2007年中-2001年末)不同人群生殖器疣新发病率变化趋势。结果疫苗时期21岁以下和21~30岁女性诊断患有生殖器疣的比例明显下降,发病率分别从2007年度的11.5%和11.3%下降至2011年度的0.85%和3.1%,P均〈0.001。在30岁以上的女性中未发现发病率的明显下降。在21岁以下和21~30岁异性恋男性人群中疫苗时期生殖器疣的发病率较前疫苗时期明显下降,分别由2007年度12.1%和18.2%下降至2011年度2.2%和8.9%,P均〈0.001。30岁以上的异性恋男性人群中发病率无明显下降。2011年235名21岁以下女性在使用HPV疫苗后无新发生殖器疣病例。结论年轻女性生殖器疣发病率的显著下降和2011年度部分年轻女性使用疫苗后的零发病率,说明HPV疫苗获得实验室外的良好功效。异性恋男性生殖器疣发病率的显著下降可能是由于群体免疫所致。 | Hammad Ali,lecturer Basil Donovan, professor HandanWand,senior lecturer Tim R H Read, sexual health physician David G Regan,senior lecturer Andrew E Grulich, professor Christopher K FaMey, professor Rebecca J Guy, associate professor 尹婕(译) 潘凌亚(校) | 2013 | 英国医学杂志中文版2013，16，4： | 4 |
| 4 | The biology of mycorrhiza in the Ericaceae Ⅷ, the role of mycorrhizal infection in heavy metal resistance显示文摘 | Bradley R Burt A J Read D J | 1982 | New Phytol1982，91，2： | 2 |
| 5 | The role of ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy显示文摘 | KD Lindor C Bru RA Jorgensen J Rakela JM Bordas JB Gross J Rodes DB McGill CC Reading EM James JW Charboneau J Ludwig KP Batts AR Zinsmeister | 1996 | Hepatology1996，，5： | 2 |
| 6 | Light-directed spatially addressable parallel chemical synthesis显示文摘 | Read J L Pirrung M C | 1991 | Science1991，251，： | 1 |
| 7 | Effect of carbon on the electronic conductivity and discharge capacity LiCoPO4显示文摘 | Wolfenstine J Read J Allen J L | 2007 | J Power Sources2007，163，2： | 1 |
| 8 | Carbonate platforms of passive(extensional) conti- nental margins: Types, characteristics and evolution 显示文摘 | Read J F | 1982 | Tectono- phys1982，81，34： | 1 |
| 9 | Severe interstitial pneumonitis associated with docetaxel administration显示文摘 | Read W L Mortimer J E Picus J | 2002 | Cancer2002，94，3： | 1 |
| 10 | Cyclostratigraphy of late Cambrian carbonate sequences 显示文摘 | Osleger D A Read J F | 1991 | SEPM1991，67，： | 1 |
| 11 | The promoter of a basic PR1-like gene,AtPRB1,from Arabidopsis establishes an organ-specific expression pattern and responsiveness to ethylene and methyl jasmonate显示文摘 | SANTAMARIA M Thomson C J Read N D | 2001 | Plant Molecular Biology2001，47，： | 1 |
| 12 | Intraosseous versus intravenous vascular access during out-of-hospital cardiac arrest:A randomized controlled trial显示文摘 | Reades R Studnek J R Vandeventer S | 2011 | Ann Emerg Med2011，58，6： | 1 |
| 13 | A functional polymorphism of Toll-like receptor 4 not associated with likelihood or severity of meningococcal disease 显示文摘 | Read RC Pullin J Gregory S | 2001 | J Infect Dis2001，184，5： | 1 |
| 14 | The shale shaker: An investor's guide to shale gas 显示文摘 | White J Read R | 2007 | Supplement to Oil and Gas Investor2007，，2： | 1 |
| 15 | Fungal specificity bottlenecks durin- gorchid germination and development 显示文摘 | BIDARTONDO M I READ D J | | Molecular Ecology0，17，16： | 1 |
| 16 | Structure of a serpin-protease complex shows inhibition by deformation显示文摘 | HUNTINGTON J A READ R J CARRELL R W | 2000 | Nature2000，407，6806： | 1 |
| 17 | Disparate bind- ing of three types of vitellogenin to multiple forms of vitellogenin re- ceptor in white perch 显示文摘 | READING B J HIRAMATSU N SULLIYAN C V | 2011 | Bid Reprod2011，84，2： | 1 |
| 18 | Treatment of the Hamman-Rich syndrome with cortisone显示文摘 | Read J Holland RA | | 0，，01： | 1 |
| 19 | High-resolution sequence stratigraphy in Tertiary carbonate-rich sections by thin-sectioned well cut-tings显示文摘 | Coffey B P Read J F | | 0，，18： | 1 |
| 20 | Invertebrate immunity and the limits of mechanistic immunology 显示文摘 | LITrLE T J HULTMARK D READ A F | 2005 | Nature Immunology2005，6，7： | 1 |
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