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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 | Polymorphisms of MTHFD,plasma homocysteine levels, and risk of gastric cancer in ahigh-risk Chinese population显示文摘Purpose:Accumulative evidence suggests that folate has a protective effect on gastric cancer. The methylenetetrahyd-rofolate dlehydrogenase(MTHFD) plays an important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD may result in disturbance of the folate-mediated homocysteine pathway. The aim of this study is to test the hypothesis that genetic variants of MTHFD and plasma homocysteine levels are associated with risk of gastric cancer and modulated by genotypes of methylenetetrahydrofolate reductase(MTHFR). Experimental Design: We genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma homocysteine(tHcy) levels in a case-control study of 589 gastric cancer cases and 635 cancer-free controls in a high-risk Chinese population. Results:The variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly increased risk of gastric canceradjusted odds ratio(OR), 2.05; 95% confidence interval(95% CI),1.34-3.13 for 1958AA; adjusted OR,1.43; 95% CI,1.14-1.80 for 401CC compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the effects were more evident in the subjects carrying MTHFR 677CT/TT genotypes. The average tHcy level was significantly higher in gastric cancer cases than in controls(P < 0.01), and the upper quartile of tHcy (> 13.6 mu mol/L) was associated with an 82% significantly increased risk of gastric cancer, compared with the lowest quartile of tHcy(<= 8.0 pmol/L;adjusted OR,1.82; 95% CI,1.20-2.75). Conclusions:The strong associations between MTHFD variants and the plasma tHcy levels and gastric cancer risk suggest, for the first time, a possible gene-environment interaction between genetic variants of folate-metabolizing genes and high tHcy levels in gastric carcinogenesis. | Wang, L. N Ke, Q Chen, W. S Wang, J. M Tan, Y. F Zhou, Y Hua, Z. L Ding, W. L Niu, J. Y Shen, J Zhang, Z. F Wang, X. R Xu, Y. H Shen, H. B Yi Xing | 2007 | 南京医科大学学报(自然科学版)2007，27，7： | 10 |
| 3 | 油炸食品与心血管病风险和全因死亡率的关系:观察性研究的荟萃分析显示文摘研究者进行了一项荟萃分析,包括剂量反应分析,以定量确定油炸食品摄入与普通成年人群心血管病风险和全因死亡率之间的关系。方法:研究者在PubMed、EMBASE和Web of Science上检索2020年4月11日之前的所有文章。应用随机效应模型估计总的相对危险度(relative risks,RR)和95%CI。结果:与最低油炸食品摄入量相比,最高摄入量者主要心血管事件的总RR(95%CI)=1.28(1.15~1.43),n=17,I^(2)=82.0%,其中前瞻性研究:1.24(1.12~1.38),n=13,I^(2)=75.7%. | 刘青(译) 练桂丽(审校) Qin P Zhang M Han M Liu D Luo X Xu L Zeng Y Chen Q Wang T Chen X Zhou Q Li Q Qie R Wu X Li Y Zhang Y Wu Y Hu D Hu F | 2021 | 中华高血压杂志2021，29，2： | 3 |
| 4 | Assay of serum arylesterase activity by fitting reaction curve with an integrated rate equation显示文摘 | Liao F Liu W L Zhou Q X | 2001 | Clin Chim Acta2001，314，12： | 2 |
| 5 | Texture feature based on local fourier transform显示文摘 | Zhou F F Shi J Q | 2001 | IEEE International Conference on ImageProcessing2001，17，2： | 2 |
| 6 | Magnetic texture in Fe nanowire array显示文摘 | Wang J B Zhou X Z Liu Q F | 2004 | Nanotecnology2004，15，： | 2 |
| 7 | RTE1 is a Golgi-assoeiated and ETR1 -dependent negative regulator of ethylene responses 显示文摘 | Zhou X Liu Q Xie F | 2007 | Plant Physiol2007，145，1： | 1 |
| 8 | Butyltin accumulation in the marine clam Mya arenaria: An evaluation of its suitability for monitoring butyltin pollutin 显示文摘 | YANG R Q ZHOU Q F JIANG G B | 2006 | Chemosphere2006，63，： | 1 |
| 9 | Comprehensive understanding on the formation of highly ordered mesoporous tungsten oxides by X-ray diffraction and Raman spectroscopy显示文摘 | Zhou L Ren Q J Zhou X F | 2008 | Microporous and MesoporousMaterials2008，109，13： | 1 |
| 10 | Prediction of groundwater inrush into coal mines from aquifers underlying the coal seams in China: vulnerability index method and its construetion显示文摘 | Wu Q Zhou W F | 2008 | Environ Geol2008，56，2： | 1 |
| 11 | Investigation of candidate VRM topologies for future microprocessors显示文摘 | Zhou X Wong P Xu P Lee F C Huang A Q | 2000 | IEEE Transactions on Power Electronics2000，15，6： | 1 |
| 12 | Proteomic analysis of hypertrophied myocardial protein patterns in renovascularly hypertensive and spontaneously hypertensive rats 显示文摘 | Zhou S G Zhou S F Huang H Q | 2006 | J Proteome Res2006，5，11： | 1 |
| 13 | 显示文摘 | Wang C F Zhou G W Xu Y Q | 2011 | Journal of PhysicalChemistry C2011，115，22： | 1 |
| 14 | Repression of choroidal neovascularization through actin cy-toskeleton pathways by microRNA-24 显示文摘 | Zhou Q Anderson C Zhang H Li X Inglis F Jayagopal A | 2014 | Mol Ther2014，22，2： | 1 |
| 15 | Comparative study of photodynamic therapy with 5%,10% and 20% aminolevulinic acid in the treatment of generalized recalcitrant facial verruca plana:a randomized clinical trial显示文摘 | Li Q Jiao B Zhou F | 2013 | J Eur Acad Dermatol Venereol2013，25，： | 1 |
| 16 | Continuous adminis- tration of recombinant human endostatin (Endostar) : a pre -clini- cal safety study显示文摘 | HUANG R F ZHAN Q ZHOU X L | 2012 | Exp Ther Med2012，3，6： | 1 |
| 17 | The TIL commissioning and performance显示文摘 | X Zhang W Zheng X Wei F Jing Z Sui K Zheng Q Xu X Yuan X Jiang L Yang P Ma M Li J Wang D Hu S He F Li Z Peng B Feng H Zhou L Guo X Li X Zhang J Su Q Zhu H Yu R Zhao C Ma H He D Fan W Zhang | 2008 | Journal of Physics: Conference Series2008，，3： | 1 |
| 18 | Continuous deposition of buffer layers for YBCO coated conductor using reactive magnetron sputtering 显示文摘 | Yang J Liu H Z Qu F Zhang H Zhou Q Gu H W | 2007 | Materials Science Forum2007，54，6549： | 1 |
| 19 | Influence of the coexisting contaminants on bisphenol A sorption and desorption in soil 显示文摘 | Li J H Zhou B X Liu Y Q Yang Q F Cai W M | 2008 | Journal of Hazardous Materials2008，151，23： | 1 |
| 20 | Structural and Magnetic Properties of Mn-Implanted Si显示文摘 | Zhou S Q Potzger K Zhang G F | 2007 | Phys Rev B2007，75，85： | 1 |
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