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| 1 | Effects of insulin and pathway inhibitors on the PI3K-Akt- mTOR phosphorylation profile in acute myeloid leukemia cells显示文摘The phosphatidylinositol 3-kinase(PI3K)-Akt-mechanistic target of rapamycin(mTOR)pathway is constitutively activated in human acute myeloid leukemia(AML)cells and is regarded as a possible therapeutic target.Insulin is an agonist of this pathway and a growth factor for AML cells.We characterized the effect of insulin on the phosphorylation of 10 mediators in the main track of the PI3K-Akt-mTOR pathway in AML cells from 76 consecutive patients.The overall results showed that insulin significantly increased the phosphorylation of all investigated mediators.However,insulin effects on the pathway activation profile varied among patients,and increased phosphorylation in all mediators was observed only in a minority of patients;in other patients,insulin had divergent effects.Global gene expression profiling and proteomic/phosphoproteomic comparisons suggested that AML cells from these two patient subsets differed with regard to AML cell differentiation,transcriptional regulation,RNA metabolism,and cellular metabolism.Strong insulin-induced phosphorylation was associated with weakened antiproliferative effects of metabolic inhibitors.PI3K,Akt,and mTOR inhibitors also caused divergent effects on the overall pathway phosphorylation profile in the presence of insulin,although PI3K and Akt inhibition caused a general reduction in Akt pT308 and 4EBP1 pT36/pT45 phosphorylation.For Akt inhibition,the phosphorylation of upstream mediators was generally increased or unaltered.In contrast,mTOR inhibition reduced mTOR pS2448 and S6 pS244 phosphorylation but increased Akt pT308 phosphorylation.In conclusion,the effects of both insulin and PI3K-Akt-mTOR inhibitors differ between AML patient subsets,and differences in insulin responsiveness are associated with differential susceptibility to metabolic targeting. | Ina Nepstad Kimberley Joanne Hatfield Ida Sofie Grønningsæter Elise Aasebø Maria Hernandez-Valladares Karen Marie Hagen Kristin Paulsen Rye Frode SBerven Frode Selheim Håkon Reikvam Øystein Bruserud | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 4 |
| 2 | 胆固醇酯转移蛋白基因的蛋白质截断型变异体与冠状动脉性心脏病风险的关系显示文摘随机对照试验结果表明,抑制胆固醇酯转运蛋白(cholesteryl ester transfer protein,CETP)的疗法并不能降低冠状动脉性心脏病(coronary heart disease,CHD)的发生风险。研究失败的可能原因包括靶目标无效、靶目标外小分子的不良反应和随机对照设计因素影响等。在编码药物靶点的基因中具有天然存在的遗传变异,以此为基础,人类研究可以深入了解针对基因产物的治疗的潜在功效和安全性。 | Nomura A Won HH Khera AV Takeuchi F Ito K McCarthy S Emdin CA Klarin D Natarajan P Zekavat SM Gupta N Peloso GM Borecki IB Teslovich TM Asselta R Duga S Merlini PA Correa A Kessler T Wilson JG Bown MJ Hall AS Braund PS Carey DJ Murray MF Kirchner HL Leader JB Lavage DR Manus JN Hartze DN Samani NJ Schunkert H Marrugat J Elosua R McPherson R Farrall M Watkins H Juang JJ Hsiung CA Lin SY Wang JS Tada H Kawashiri MA Inazu A Yamagishi M Katsuya T Nakashima E Nakatochi M Yamamoto K Yokota M Momozawa Y Rotter JI Lander ES Rader DJ Danesh J Ardissino D Gabriel S Willer CJ Abecasis GR Saleheen D Kubo M Kato N Ida Chen YD Dewey FE Kathiresan S 刘莉 叶鹏 | 2017 | 中华高血压杂志2017，25，9： | 2 |
| 3 | Estimation of tibiofemoral static zero position during dynamic drop landing显示文摘 | Ida H Nagano Y Akai M | 2013 | The Knee2013，20，5： | 1 |
| 4 | Clinical and genetic studies of Japanese homozygotes disease L444P muta- tion显示文摘 | IDA H RENNERT O M IWASAWA K | 1999 | Hum Genet1999，105，12： | 1 |
| 5 | Clinical outcome of surgical per-iodontal therapy:a short-term retrospective study显示文摘 | Hayakawa H Fujinami K Ida A | | 0，，04： | 1 |
| 6 | Real-time PCR for quantification of streptococcus mutans显示文摘 | YanoA Kaneko N Ida H | 2002 | Fems Microbiol Letl2002，217，1： | 1 |
| 7 | Molecular characteristics of the CA 125 antigen produced by human endometrial epithelial calls : comparison between eutopic and heterotopie epithelial cells显示文摘 | Kobagashi H Ida W Terao T | 1993 | Am J Obstet Gynecol1993，169，3： | 1 |
| 8 | Real-time PGR for quantification of Streptococcus mutans显示文摘 | Yano A Kaneko N Ida H Yamaguchi T | 2002 | FEMS Microbiol Lett2002，217，1： | 1 |
| 9 | Adult intestinal intussusception caused by an inflammatory myofibroblastic tumor显示文摘 | Ida S Matsuzaki H Kawashima S | | 0，，2： | 1 |
| 10 | An object-oriented database system jasmine:implementation,application,and extension显示文摘 | Ishikawa H Yamame Y Izum Ida Y | 1996 | IEEE Transaction Knowledge and Data Engineering1996，8，2： | 1 |
| 11 | Analyses of promoter hypermethylation for RUNX3 and other tumor suppressor genes in nasopharyneal carcinoma显示文摘 | Tan SH Ida H Goh BC | 2006 | Anticancer Research2006，26，6： | 1 |
| 12 | Catalytic activity of PAN-based active carbon fibre (PAN-ACF) activated with sulphuric acid for reduction of nitric oxide with ammonia显示文摘 | Komatsumara Y Ida S Fujitsu H | 1984 | Fuel1984，63，12： | 1 |
| 13 | Renal transport of adefovir,cidofovir,and tenofovir by SLC22 family members (hOAT1,hOAT3,and hOCT2)显示文摘 | Uwai Y Ida H Tsuji Y | | 0，，4： | 1 |
| 14 | RPE cells modulate subretinal neovascularization, but do not cause regression in mice with sustained expression of VEGF显示文摘 | Tobe T Nambu H | 2003 | Invest Ophthalmol Vis Sci2003，44，12： | 1 |
| 15 | Staging of idiopathic choroidal neovascularization by optical coherence tomography 显示文摘 | Fukuchi T Takahashi K Ida H | 2001 | Graefe''s Arch Clin Exp Ophthalmol2001，239，： | 1 |
| 16 | Molecular characteristics of the CAI 25 antigen produced by humen heteritopic epithelial cells:comparison between eutopic and herterotopic epithelium显示文摘 | Kobayashi H Ida W Terao T | 1993 | Am Jobstet Gynecol1993，169，： | 1 |
| 17 | Extended pseudo-Voigt function for approximating the Voigt profile显示文摘 | IDA T ANDO M TORAYA H | 2000 | J Appl Cryst2000，33，： | 1 |
| 18 | Detection of promoter hypermethylation in serum samples of cancer patients by methylation-specific polymerase chain reaction for tumour suppressor genes including RUNX3显示文摘 | Tan SH Ida H Lau QC | 2007 | Oncol Rep2007，18，5： | 1 |
| 19 | Analyses of promoter hypenne-thylation for RUNX3 and other tumor suppressor genes in nasopha-ryngeal carcinoma显示文摘 | TAN S H IDA H GOH B C | 2006 | Anticancer Res2006，26，6： | 1 |
| 20 | Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling显示文摘 | Ida T Sawa T Ihara H Tsuchiya Y Watanabe Y Kumagai Y Suematsu M Motohashi H Fujii S Matsunaga T Yamamoto M Ono K Devarie O N Xian M Fukuto M F Akaike T | 2014 | Proceedings of the National Academy of Sciences2014，111，21： | 1 |
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