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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 | A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response显示文摘病毒的 RNA 的识别由 cytosolic 传感器 retinoic 组织酸可诱导的基因 --(RIG-I ) 我导致表明与类型的产生达到顶点的串联的激活我干扰素(IFN ) 抗病毒的反应。对病毒的病原体的抗病毒、煽动性的回答的发作要求表明改编者, kinases 和 transcriptional 蛋白质到 mitochondrial 的调整空间与时间的招募抗病毒的发信号蛋白质(MAVS ) 。我们以前示威了 serine/threonine kinase IKKε被招募到 MAVS 后面的仙台或小囊的口炎病毒(VSV ) 感染的 C 终端区域,在 Lys500 由 MAVS 的连接 Lys63 的 polyubiquitination 调停了,导致下游的 IFN 发信号的抑制(Paz 等,摩尔房间 Biol, 2009 ) 。在这研究,我们证明 MAVS 的 C 终点在 MAVS 的 aa450-468 区域怀有一个新奇 TRAF3 有约束力的地点。一个一致交往 TRAF 主题(提姆) , 455-PEENEY-460,在这以内,地点为 TRAF3 绑定和 IFN 抗病毒的反应基因的激活被要求,而 TIM 的变化消除 TRAF3 绑定和下游的 IFN 反应。有表示 MAVS 的一个变异提姆的版本的构造的 MAVS −/− 老鼠胚胎成纤维细胞的宪法没能恢复抗病毒的反应或块 VSV 复制,而野类型的 MAVS 重新组成 VSV 复制的抗病毒的抑制。而且, IKKε 的招募;到在经由 Lys500 的 MAVS 的一个邻近的 C 终端地点(aa 468-540 ) , ubiquitination 减少了 TRAF3 绑定和蛋白质稳定性,因此贡献 IKKε调停 IFN 反应关机。这研究证明 MAVS 怀有功能的 C 终端参予 IFN 抗病毒的反应的积极、否定的规定的 TRAF3 有约束力的地点。 | Suzanne Paz Myriam Vilasco Steven J Werden Meztli Arguello Deshanthe Joseph-Pillai Tiejun Zhao Thi Lien-Anh Nguyen Qiang Sun Eliane F Meurs Rongtuan Lin John Hiscott | 2011 | Cell Research2011，21，6： | 12 |
| 3 | Effects of luteinizing hormone and androgen on the development of rat progenitor Leydig cells in vitro and in vivo显示文摘祖先 Leydig 房间从干细胞被导出。祖先 Leydig 房间的增长和区别显著地在发身期间贡献 Leydig 房间数字。然而,这些过程的规定仍然保持不清楚。现在的学习的目的是决定 luteinizing 荷尔蒙(LH ) 或雄激素是否贡献祖先 Leydig 房间的增长和区别。Fourteen-day-old 男 Sprague-Dawley 老鼠与 NalGlu 被对待 7 天,它是一个释放 gonadotropin 荷尔蒙对手,到在垂体并且这样减少 LH 的分泌物,在睾丸的雄激素。老鼠与 LH 或 7 α 被共同管理; -methyl-nortestosterone (MENT ) 是对由 5 α 的新陈代谢抵抗的雄激素, -reductase 1 在祖先 Leydig 房间,和 LH 或雄激素的随后的效果被测量。3 H-Thymidine 静脉内地也被注入老鼠在祖先 Leydig 房间学习 thymidine 加入。祖先 Leydig 房间被检验。NalGlu 管理由 83 % 减少了祖先 Leydig 房间增长;。另外, LH 或 MENT 处理恢复了 Leydig 房间 proliferative 能力到 73 %或 50 %控制,分别地。增长相关的基因的送信人 RNA 层次用即时 PCR 被测量。Igf1, Lifr, Pdgfra, Bcl2, Ccnd3 和 Pcna 的表示层次是由 MENT 的 upregulated,并且 Pdgfra, Ccnd3 和 Pcna 的那些是由 LH 的 upregulated。LH 和 MENT 在 vitro 刺激了祖先 Leydig 房间的区别。我们断定 LH 和 MENT 涉及调整祖先 Leydig 房间的发展。 | Jing-Jing Guo Xue Ma Claire Q F Wang Yu-Fei Ge Qing-Quan Lian Dianne O Hard Yu-Fei Zhang Qiang Dong Yun-Fei Xu Ren-Shan Ge | 2013 | Asian Journal of Andrology2013，15，5： | 4 |
| 4 | Development of a reverse transcription quantitative polymerase chain reaction-based assay for broad coverage detection of African and Asian Zika virus lineages显示文摘The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions. | Yang Yang Gary Wong Baoguo Ye Shihua Li Shanqin Li Haixia Zheng Qiang Wang Mifang Liang George F Gao Lei Liu Yingxia Liu Yuhai Bi | 2017 | Virologica Sinica2017，32，3： | 3 |
| 5 | Post-fire mechanical properties of high strength structural steels $460 and $690 显示文摘 | Qiang X Bijlaard F S K Kolstein H | 2012 | Engineering Structures2012，35，： | 1 |
| 6 | Nurses' experiences with catas-trophic upper gastrointestinal bleeding in patients with hepatocellu-lar carcinoma: A qualitative study 显示文摘 | Zheng R Dong F Qiang W | 2013 | Eur J Oncol Nurs2013，17，4： | 1 |
| 7 | Compact optical temporal differentiator based on silicon microring resonator显示文摘 | Liu F F Wang T Qiang L Ye T Zhang Z Qiu M Su Y | | 0，，20： | 1 |
| 8 | Effect of Working Current on Mierostructure and Properties of Cylinder Hardened by Plasma Beam at Junction of the Hardening Traces 显示文摘 | Yang L Qiang Y H Chen F S | 2011 | Advanced Materials Research2011，314，： | 1 |
| 9 | Early immune outcome of retroperitoneal laparoscopic radical nephrectomy for localized renal cell carcinoma:a prospective,randomized study显示文摘 | LU Y TIANYONG F QIANG W | 2012 | Can Urol Assoc J2012，6，6： | 1 |
| 10 | Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure显示文摘 | Adamopoulos S Plepoli M Qiang F | 2003 | Lancet2003，26，9： | 1 |
| 11 | Recent large reduction in sulfur dioxide emissions from Chinese power plants observed by the Ozone Monitoring Instrument显示文摘 | Li Can Zhang Qiang Krotkov Nickolay A. Streets David G. He Kebin Tsay Si-Chee Gleason James F | 2010 | Geophysical Research Letters2010，，8： | 1 |
| 12 | Post-fire performance of very high strength steel $960 显示文摘 | Qiang X Bijlaard F S K Kolstein H | 2013 | Journal of Constructional Steel Research2013，80，1： | 1 |
| 13 | Study on the Correlation between Blood Enzyme Activity and Production Performance in Tibetan Yaks 显示文摘 | Xie Z Qiang Ba Y Z | 2003 | Developmental & Reproductive Biology2003，11，1： | 1 |
| 14 | CHAMP Orbit Determination and Gravity Field Recovery 显示文摘 | MOORE P TURNER J F QIANG Z | 2003 | Adv Space Res2003，31，8： | 1 |
| 15 | Thermophysicla proper- ties of complex rare-earth zirconate ceramic for thermal barrier coatings 显示文摘 | Ling L Qiang X Chi W F | 2008 | Journal of American Ceramic Society2008，，91： | 1 |
| 16 | Evaluation of the flavor-- noid oroxylin A as an inhibitor of P--glycoprotein--mediated cellular efflux-- 显示文摘 | Go W J Ryu J H Qiang F | 2009 | JNatProd2009，72，9： | 1 |
| 17 | Genetic Algorithms Applied to The Adaptation of IIR Filters显示文摘 | Ma Qiang Colin F N Cowan | 1996 | Signal Processing1996，48，： | 1 |
| 18 | A fast algorithm for determining the Gaussian filtered mean line in surface metrology显示文摘 | Yuan Y B Qiang X F Song J F | | 0，，： | 1 |
| 19 | Isolation and phytotoxicity of a metabolite from Curvularia eragrostidis and characterisation of its modes of action显示文摘 | Qiang S Zhu Y Z Dong Y F | 2008 | Annals of Applied Biology2008，152，1： | 1 |
| 20 | Composite element model of the fully grouted rock bolt显示文摘 | CHEN S H QIANG S CHEN S F | 2004 | Rock Mechanics and Rock Engineering2004，37，3： | 1 |
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