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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 | Late Quaternary palaeoenvironmental changes documented by microfaunas and shell stable isotopes in the southern Pearl River Delta plain,South China显示文摘Ahigh resolution study of sediments,microfaunas(ostracods and foraminifers),and stable isotopes of ostracod shells from core PRD05,sampled from the Da’ao plain of the Pearl River Delta,provides new data about palaeoenvironmental changes during the Late Quaternary.The basal fluvial gravelly sediments of the core,representing the lowest deposits of the Quaternary at the core site,were possibly formed prior to the transgression associated with the last interglacial stage.This fluvial setting changed into a marginal marine setting during the last interglacial stage,any record of calcareous fossils were destroyed by subsequent dissolution during the last glacial phase,when the upper part of the deltaic sediments experienced subaerial oxidation,indicated by a mottled clay layer in the core.The postglacial sealevel rise in the South China Sea began at16,700 cal yr B.P.During the first phase of sea-level rise(from ~16,700 to 10,100 cal yr B.P.),a swamp environment developed at the core site.At ~10,100 cal yr B.P.,marine waters intruded onto the Da’ao plain and reached the core site through the Modaomen channel.This timing was earlier than in other parts of the Pearl River Delta.Since then,a semi-enclosed estuarine environment developed and was maintained until ~5560 cal yr B.P.During this transgressive interval,short-term environmental fluctuations can be recognized based on microfauna and shell geochemical data.From ~10,100 to 8630 cal yr B.P.,the sea-level rose,which was followed by a fall from ~8630 to 8520 cal yr B.P.An expanded transgression occurred between ~8520 and 7900 cal yr B.P.The time intervals from ~8520 to 8200 cal yr B.P.and from ~8080 to 7900 cal yr B.P.were marked by peak transgression.From ~7900 to 5560 cal yr B.P.,the core site generally showed a reduced marine influence and enhanced freshwater input.A fluvial environment developed from ~5560 to 3100 cal yr B.P.,and was succeeded by an alluvial plain setting. | Liu Chunlian Franz T. Fürsich Wu Jie Dong Yixin Yang Tingting Yin Jian | 2013 | Journal of Palaeogeography2013，2，4： | 8 |
| 3 | Identification and characterization of the minimal androgen-regulated kidney-specific kidney androgen-regulated protein gene promoter显示文摘肾调整雄激素的蛋白质(Kap ) 基因是由雄激素在老鼠肾特定、调整的织物近似小管房间(PTC ) 。在现在的学习,我们试图识别最小的 PTC 特定的调整雄激素的 Kap 倡导者并且分析它的雄激素反应元素(AREs ) 。Kap1542 倡导者 / 酶构造的一个删除系列是 assayed 在里面鼠肾(好) PTC 当面或 15 nM dihydrotestosterone (DHT ) 的缺席。Kap1542 和 Kap637 举办了低活动和没有雄激素正式就职;Kap224 举办了比 Kap1542 的高是到 5 褶层的 4- 的一项基础活动,但是被 DHT 仅仅稍微导致。Kap147 举办了比 Kap1542 的高是到 3 褶层的 2- 并且被 DHT 4- 导致到 6 褶层的一项基础活动。Kap77 废除了基础倡导者活动,但是被 DHT 仍然导致。结果证明在 vitro, Kap147 是一个最小的调整雄激素的倡导者。在不同房间的短暂 transfection 证明 Kap147 明确地在 PTC 开始了记者基因表示。顺序分析揭示了在位置 −124 和 Kap147 的 −39 定位的二潜在的 AREs。Mutational 试金证明仅仅在 −124 的 ARE 在好房间涉及雄激素反应。Electrophoretic 活动性移动试金也证实 −124 雄激素受体明确地一定。在结论,我们定义可以是为肾的学习的一个好模型的最小的 Kap147 倡导者在 vivo 导致一只雄激素特定的应答的海角的 PTC 特定的表示和分子的机制。 | Liqiang Fan Dianne O Hardy James F Catteral Jian Zhao Suxia Li | 2008 | Acta Biochimica et Biophysica Sinica2008，40，12： | 4 |
| 4 | Alkaline syenites in eastern Cathaysia (South China): Link to Permian-Triassic transtension显示文摘 | Wang Q Li J W Jian P Zhao Z H Xiong X L Bao Z W Xu J F Li C F Ma J L | 2005 | Emth Planet Sci Lett2005，230，34： | 1 |
| 5 | Two dimensional PCA: a new approach to appearance based face represention and recognition 显示文摘 | Yang Jian Zhang D Frangi A F | 2004 | IEEE Trans on Pattern Analysis and Machine Intelligence2004，26，1： | 1 |
| 6 | Hydrothermal preparation and visible-light photoeatalytie activity of Bi2WO6 powders 显示文摘 | Jia G Y Jian F X Bei C | 2005 | Solid State Chem2005，178，： | 1 |
| 7 | Structures,thermal stabilities,and magnetic properties of four new lanthanide coordinative frameworks incorporating mixed organic ligands显示文摘 | Jian B R Liu H C Lin Y W Huang S C Hsu K F | | 0，，1： | 1 |
| 8 | Isolation of a strain of Acidithiobacillus caldus and its role in bioleaching of chalcopyrite显示文摘 | ZHOU Q G BO F BO Z H XI L JIAN G FEI L F HUA C X | 2007 | World Journal of Microbiology and Biotechnology2007，23，9： | 1 |
| 9 | Kinetic processes of photoeatalytic mineralization of alcohols on metallized titanium dioxide显示文摘 | Chen Jian Ollis David F Rulkens Wire H | 1999 | Water Research1999，33，5： | 1 |
| 10 | Uptake system of silicon in different plant species 显示文摘 | MITANI N JIAN F M | 2005 | Journal of Experimental Botany2005，56，414： | 1 |
| 11 | KPCA plus LDA:a complete kernel Fisher discriminant framework for feature extraction and recognition显示文摘 | YANG Jian FRANGI A F YANG Jing-yu | 2005 | IEEE Trans on Pattern Analysis and Machine Intelligence2005，27，2： | 1 |
| 12 | Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization显示文摘 | Lieben Liesbet Masuyama Ritsuko Torrekens Sophie Van Looveren Riet Schrooten Jan Baatsen Pieter Lafage-Proust Marie-Hélène Dresselaers Tom Feng Jian Q Bonewald Lynda F Meyer Mark B Pike J Wesley Bouillon Roger Carmeliet Geert | 2012 | EN2012，，5： | 1 |
| 13 | Petrogenesis of adakitic porphyries in an extensional tectonic setting, Dexing, South China:Imphcations for the genesis of porphyry copper mineralization 显示文摘 | Wang q Xu J F Jian P | 2006 | Journal of Petrology2006，47，： | 1 |
| 14 | Environmental adaptation:genomic analysis of the piezotolerant and psychrotolerant deep-sea iron reducing bacterium Shewanella piezotolerans WP3显示文摘 | Wang F Wang J Jian H | 2008 | PLOS ONE2008，3，： | 1 |
| 15 | Quantitation of HERV-K env gene expression and splicing in human breast cancer显示文摘 | Wang-Johanning F Frost AR Jian B | 2003 | Oncogene2003，22，10： | 1 |
| 16 | Novel Range-Spread Tar- get Detectors in Non-Gaussian Clutter 显示文摘 | He Y Jian T Su F | 2010 | IEEE Trans on Aerospace and Electronic Systems2010，46，3： | 1 |
| 17 | A compara- tive study of growth performance and antioxidant sta- tus of rabbits when fed with or without chestnut tan- nins under high ambient temperature 显示文摘 | LIU H W XIAO F D JIAN M T | 2011 | Animal Feed Science and Technology2011，164，： | 1 |
| 18 | Two-dimensional PCA:A New Approach to Appearance Based Face Representation and Recognition显示文摘 | YANG Jian ZHANG D FRANGI A F | | 0，，01： | 1 |
| 19 | KPCA plus LDA:A complete kernel Fisher discriminated framework for feature extraction and recognition显示文摘 | YANG JIAN FRANGI A F YANG JINGYU | | 0，，02： | 1 |
| 20 | A study of purified montmorillonite intercalated with 5-fluorouracil as drug cartier显示文摘 | Lin F H Lee Y H Jian C H | 2002 | Biomaterials2002，23，9： | 1 |
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