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| 1 | Analysis of the phosphatidylinosit ol 3'-kinase signaling pathway in glioblastoma patients in vivo显示文摘Deregulated signaling through the p hosphatidylinositol 3-kinase(PI3K)pathway is common in many types of can cer,including glioblastoma.Dissecting the molecular events associated with activation of this pathway in glioblastoma p atients in vivo presents an important challenge that has implic ations for the development and clini cal testing of PI3K pathway inhibito rs.Using an immunohistochemical analysis appl ied to a tissue microarray,we performed hierarchical clustering and mul tidimensional scaling,as well as univariate and multivariate analyses,to dissect the PI3K pathway in v ivo.We demonstrate that loss of the t umor suppressor protein PTEN,which antagonizes PI3K pathwa y activation,is highly correlated w ith activation of the main PI3K effec tor Akt in vivo.We also show that Akt activation is signific antly correlated with phosphorylation of mammalian target of rapamycin(mTOR),the family of forkhead transcription factors(FOXO1,FOXO3a,and FOXO4),and S6,which are thought to promote its effects.Expression of the mutan t epidermal growth factor receptor vIII is also tightly correlated with phosphorylation of these effectors,d emonstrating an additional route to PI3K pathway activation in glioblastomas in vivo.These results provide the first dissection of the PI3K path way in glioblastoma in vivo and suggest an approach to stratifying patients for targeted kinase inhi bitor | Choe G Horvath S Cloughesy TF Crosby K Seligson D Palotie A Inge L Smith BL Sawyers CL Mischel PS | 2003 | 癌症2003，22，7： | 41 |
| 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 | Watershed infarcts in transient ischemic attack/minor stroke with > or 50o/00 carotid stenosis: hemodynamic or embolie? 显示文摘 | Moustafa RR Izquierdo Garcia D Jones PS | 2010 | Stroke2010，41，7： | 1 |
| 4 | Preliminary pharmaco- kinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil显示文摘 | Glass PS Hardman D Kamiyama Y | 1993 | Anesth Analg1993，77，5： | 1 |
| 5 | Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid:remifentanil (GI87084B)显示文摘 | Glass PS Hardman D Kanmiyama Y | 1993 | Anesth Analg1993，77，15： | 1 |
| 6 | Safety and Immunogenici- ty of human papillomavirus-16/18 AS04-adjuvanted vaccine: A randomized trial in 10--25-year--old HIV seronegative African girls and young women显示文摘 | Sow PS Watson-Jones D Kiviat N | 2013 | J Infect Dis2013，207，11： | 1 |
| 7 | Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension 显示文摘 | Kerstein D Levy PS Hsu DT | 1995 | Circulation1995，91，7： | 1 |
| 8 | SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia显示文摘 | Sasca D Hahnel PS Szybinski J | 2014 | Blood2014，124，1： | 1 |
| 9 | Cardioprotective effects of acidified sodium nitrite in myocardial ischemia with reperfusion显示文摘 | Johnson ⅢG Tsao PS Mullory D | 1990 | J Pharmacol Exp Ther1990，252，1： | 1 |
| 10 | Proline biosynthesis and osmreyulation in plants 显示文摘 | Verma D PS | 1995 | plant J1995，108，： | 1 |
| 11 | Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material 显示文摘 | Walsh PS Metzger D Higuchi R | 1991 | Biotechniques1991，10，： | 1 |
| 12 | Diethylstilbestrol and docetaxel:a PhaseⅡ study of tubulin active agents in patents with metastatic,androgen-independent prostate cancer显示文摘 | Montgomery RB Nelson PS lin D Ryan CW Garzotto M Beer TM | 2007 | Cancer2007，110，5： | 1 |
| 13 | Pregnancy-induced hypertension: deve lopment of a model in the pregnant primate(Papio anubis)显示文摘 | Cavanagh D Rao PS Knuppel RA | 1985 | Am J Obstet Gyne col1985，151，7： | 1 |
| 14 | Imaging biomarkers of outcome in the developing preterm brain显示文摘 | Ment LR Hirtz D Huppi PS | 2009 | Lancet Neurol2009，8，11： | 1 |
| 15 | A randomized trial of intraarterial treatment for acute ischemic stroke 显示文摘 | Berkhemer OA Fransen PS Beumer D et 81 | 2015 | N Engl J Med2015，372，1： | 1 |
| 16 | Chromosomal and ge-netic alterations in human hepatocellular adenomas associatedwith type I a glycogen storage disease 显示文摘 | Kishnani PS Chuang TP Bali D | 2009 | Hum Mol Genet2009，18，47： | 1 |
| 17 | The chemokine and scavenger receptor XCXL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon gamma显示文摘 | Wagsater D Olofsson PS Norgren L | 2004 | Biochem Biophys Res Commun2004，325，4： | 1 |
| 18 | Isoflurane, but not halothane improves indices of diastolic performance in dogs with rapid ven- tricular pacing induced cardiomyopathy 显示文摘 | Pagel PS Lowe D Heltrick DA | 1996 | Anesthesiology1996，85，3： | 1 |
| 19 | The effect of acidified enteral feeds on gastric colonization in critically ill patients: Results of a multieenter random- ized trial, Critical Care Medicine 显示文摘 | Heyland DK Cook D J Schoenfeld PS | 1999 | Crit Care Med1999，27，11： | 1 |
| 20 | Watershed infarcts in transient ischemic attack/minor stroke with > or = 50% carotid stenosis: hemodynamic or embohc? 显示文摘 | Moustafa RR Izquierdo-Gareia D Jones PS | 2010 | Stroke2010，41，7： | 1 |
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