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| 1 | Biomarker-guided sequential targeted therapies to overcome therapy resistance in rapidly evolving highly aggressive mammary tumors显示文摘组合指向的治疗在由堵住治疗癌症是更有效的绕过机制或导致的合成致命性。然而,他们的临床的申请被抵抗和毒性妨碍。遇见这重要挑战,我们用 ErbB2-overexpressing/PTEN-low 开发了并且测试各种各样的指向的治疗的指导 biomarker 的顺序的应用程序的一个新奇概念,高度好攻击的乳癌作为我们的模型。惊人地,从遗传上设计的鼠标与 intratumoral 异质从病人和乳房的肿瘤在两 PTEN-low/trastuzumab-resistant 乳癌支撑了 ErbB2 和下游的小径驱动器 trastuzumab 抵抗的激活。尽管 lapatinib 开始禁止了 trastuzumab 抵抗的鼠标肿瘤,肿瘤由激活表明由量的蛋白质数组出现的网络的 PI3K/mTOR 绕过抑制。有趣地,小径也是的 mTOR 的激活在 neoadjuvant 观察了表明 lapatinib 抵抗的对待 lapatinib 的病人。Trastuzumab + lapatinib 抵抗被一个 PI3K/mTOR 双 kinase 禁止者(BEZ235 ) 的顺序的申请有效地没有重要毒性克服。然而,我们的 p-RTK 数组分析证明 BEZ235 治疗在遗传上设计的老鼠肿瘤导致了增加的 ErbB2 表示和 phosphorylation,导致 BEZ235 抵抗并且在 3-D,然而并非 2-D,文化。机械学地,我们作为 BEZ235 抵抗的新奇机制识别了 ErbB2 蛋白质稳定和激活,它被随后的治疗与 lapatinib + BEZ235 联合颠倒。显著地, biomarker 指导的指向的治疗的这个顺序的应用程序在很快发展加倍的抵抗的肿瘤改变忍受极其好攻击的肿瘤的鼠标的寿命。使用的这条根本上新奇的途径有效地在一个顺序的顺序罐头指向了治疗目标和改编在在治疗期间发展抵抗的癌症的发信号的网络。 | Ozgur Sahin Qingfei Wang Samuel W Brady Kenneth Ellis Hai Wang Chia-Chi Chang Qingling Zhang Preety Priya Rui Zhu Stephen T Wong Melissa D Landis William J Muller Francisco J Esteva Jenny Chang Dihua Yu | 2014 | Cell Research2014，24，5： | 2 |
| 2 | In vitro alterations of intestinal bacterial microbiota in fecal samples during storage显示文摘 | Stephan J O Meike M Kenneth N T | 2004 | Diagnostic Microbiology and Infectious Disease2004，50，： | 1 |
| 3 | Amphiphilic templating of magnesium hydroxide显示文摘 | Ranjit K T Kenneth K J | 2005 | Langmuir2005，21，12： | 1 |
| 4 | Amphiphilic Templating of Magnesiu Hydroxide 显示文摘 | Ranjit K T Kenneth K J | 2005 | Langmuir2005，21，12： | 1 |
| 5 | Agar like polysaccharide produced by a Pseudomonas species production and basic properties显示文摘 | Kenneth S Kang George T Veeder Peter J Mirrasoul | 1982 | Applied and Environment Microbiology1982，43，5： | 1 |
| 6 | Managerial ownership, Accounting choices and Informativeness of earnings 显示文摘 | Warfield T D John J Wild Kenneth L Wild | 1995 | Journal of Accounting and Economics1995，，7： | 1 |
| 7 | Analysis of relative gene expressiondata using real-time quanti-tative PCR and the 2-△△Ctmethod显示文摘 | KENNETH J LIVAK T D | 2001 | Method2001，25，： | 1 |
| 8 | Global health 2035: a world converging within a generation显示文摘 | Dean T Jamison Lawrence H Summers George Alleyne Kenneth J Arrow Seth Berkley Agnes Binagwaho Flavia Bustreo David Evans Richard G A Feachem Julio Frenk Gargee Ghosh Sue J Goldie Yan Guo Sanjeev Gupta Richard Horton Margaret E Kruk Adel Mahmoud Linah K Mo | 2013 | 2013 (9908)2013，，9908： | 1 |
| 9 | Longevity of granular iron in groundwater treatment processes:corrosion product development显示文摘 | KOHN T KENNETH J T ROBERTS A L | 2005 | Environmental Science & Technology2005，39，8： | 1 |
| 10 | Synthesis,transition temperatures,and optical properties of compounds with simple phenyl units linked by double bond,triple bond,ester or propiolate linkages显示文摘 | Gregory J C Alexander J S Kenneth J T | 2000 | Journal of Materials Chemistry2000，10，7： | 1 |
| 11 | Distal Radius Fractures显示文摘 | Frank A Liporace Mark R Adams John T Capo Kenneth J Koval | 2009 | Journal of Orthopaedic Trauma2009，，10： | 1 |
| 12 | Unsedated ultrathin EGD is well accepted when compared with conventional sedated EGD: a multicenter randomized trial显示文摘 | Ruel T Garcia John P Cello Mindie H Nguyen Stanley J Rogers Alex Rodas Huy N Trinh Neil H Stollman Gail Schlueck Kenneth R McQuaid | 2003 | Gastroenterology2003，，6： | 1 |
| 13 | Visualization in 3-D seismic interpretation显示文摘 | Geoffrey A D Mary J C Kenneth M T | 1995 | The Leading Edge1995，14，10： | 1 |
| 14 | Three unrelated viral transforming proteins (vIRF,EBNA2,andEIA) induce the MYC oncogene through the interferon-responsive PRF element by using different transcription coadaptors显示文摘 | SUKHANYA J KENNETH G L AI-EN T | 1999 | Proc Natl Acad Sci USA1999，96，11： | 1 |
| 15 | In vitro alterations of intestinal bacterial microbiota in fecal samples during storage 显示文摘 | STEPHAN J O MEIKE M KENNETH N T | 2004 | Diagnostic Microbiology and Infectious Disease2004，50，： | 1 |
| 16 | A simplified system for generating recombinant adenoviruses显示文摘 | He T C Zhou S B Luis T Costa D Yu J Kenneth W Kinzler Vogelstein B | | 0，，： | 1 |
| 17 | A note on reserve requirements and monetary control with a flexible deposit rate 显示文摘 | RICHARD T KENNETH J K | 1983 | Journal of Banking & Finance1983，，7： | 1 |
| 18 | Effective targeting of lipesomes to liver and hepatocytes in vivo by incorporation of a plasmodium amino acid sequence显示文摘 | KENNETH J LONGMUIR RICHARD T ROBiN SHERRY M HAYNES | 2006 | Pharmaceutical Research2006，23，： | 1 |
| 19 | Comparison of different standards for real-time PCR-based absolute quantifica- tion 显示文摘 | Dhanasekaran S Doherty T M Kenneth J | 2010 | J Immunol Methods2010，354，： | 1 |
| 20 | Analysis of relative gene expression data using real-time quantitative PCR and the 2 aaCV method显示文摘 | Kenneth J Livaka T Schmittgen D | 2001 | Methods2001，25，4： | 1 |
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