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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 | Chromism and luminescence in regioregular poly(3-dodecylthiophene)显示文摘 | Rumbles G Samuel I D W Magnani L | 1996 | Synthetic Metals1996，76，： | 1 |
| 3 | Femtosecond transient absorption measurements in poly(arylenevinylene)s 显示文摘 | Samuel D W Raksi F Bradley D D C | 1993 | Synthetic Metals1993，，55： | 1 |
| 4 | A photoactivatable push-pull fluorophore for single-molecule imaging in live cells显示文摘 | Lord S J Conley N R Lee H L D Samuel R Liu N Twieg R J Moerner W E | | 0，，29： | 1 |
| 5 | Colorectal cancer: mutations in a signalling pathway 显示文摘 | PARSONS D W WANG T L SAMUELS Y | 2005 | Nature2005，436，7052： | 1 |
| 6 | The Development of Light-Emitting Dendrimers for Displays 显示文摘 | BURN PAUL LO SHIH CHUN SAMUEL IFOR D W | 2007 | AdvMater2007，19，： | 1 |
| 7 | Phar- maceutical cocrystallization: engineering a remedy for caffeine hydration显示文摘 | Trask Andrew V Samuel Motherwell W D William Jones | 2005 | Crystal Growth &Design2005，5，3： | 1 |
| 8 | Phar- maceutical cocrystals: an emerging approach to physical proper- ty enhancement显示文摘 | Jones William Samuel Motherwell W D Trask Andrew V | 2006 | MRS Bulletin2006，31，11： | 1 |
| 9 | Mutations in filamin 1 Prevent Migration of Cerebral Cortical Neurons in Human Periventricular Heterotopia显示文摘 | Jeremy W Fox Edward D Lamperti Yaman Z Ek?io?lu Susan E Hong Yuanyi Feng Donna A Graham Ingrid E Scheffer William B Dobyns Betsy A Hirsch Rodney A Radtke Samuel F Berkovic Peter R Huttenlocher Christopher A Walsh | 1998 | Neuron1998，，6： | 1 |
| 10 | Three-phase percolative silver-BaTiO3-epoxy nanocomposites with high dielectric constants显示文摘 | LAI Q LEE B I SAMUELS W D | 2006 | J Appl Polym Sci2006，102，2： | 1 |
| 11 | Trends of winter nurtitionalk restriction, ticks, and numbers of moose on Isle Royale显示文摘 | DelGiudice G D Peterson R O Samuel W M | 1997 | J Wildl Manage1997，61，： | 1 |
| 12 | Synthesis of enzymatically active human α-- L-- iduronidase in Arabidopsis cgI ( complex glyean -- deficient) seeds 显示文摘 | Downing W L Galpin J D Clemens S Lauzon S M Samuels A L Pidkowich M S Clarke L A and Kermode A R | 2006 | Plant Biotechnology Journal2006，4，： | 1 |
| 13 | Genetic relationships between foot-and-mouth disease type Asia I viruses显示文摘 | Ansell D M Samuel A R Carpenter W C | 1994 | Epidemiol Infect1994，112，： | 1 |
| 14 | Adsorption and degradation of zearalenone by bacillus strains显示文摘 | Samuel E T Cuthbert W Xu D | | 0，，04： | 1 |
| 15 | Light out-coupling efficiencies of organic light-emitting diode structures and the effect of photoluminescence quantum yield显示文摘 | Smith L H Wasey J A E Samuel D W | 2005 | Advanced Functional Material2005，15，11： | 1 |
| 16 | Molecular bio-markers for breast cancer prognosis:coexpression of C-erbB-2 and p53显示文摘 | Samuel W B William E G Crowe D R | 2001 | Ann Surg2001，233，5： | 1 |
| 17 | 查看详情显示文摘 | Namdas E B Ruseckas A Samuel D W | | 0，，： | 1 |
| 18 | Production of alpha-1, 3-galactosyltransferase knockout pigs by nuclear transfer cloning显示文摘 | Lai L Kolber-Simonds D Park K W Cheong H T Greenstein J L Im G S Samuel M Bonk A Rieke A DayB N Murphy C N Carter D B Hawley R J Prather R S | 2002 | Science2002，295，5557： | 1 |
| 19 | Surface plasmon-polariton mediated emission from phosphorescent dendrimer light-emitting diodes 显示文摘 | Yates C J Samuel I D W Burn P L | 2006 | Appl Phys Lett2006，88，16： | 1 |
| 20 | An oil spill trajectory analysis model with a variable wind deflection angle 显示文摘 | SAMUELS W B HUANG N E AMSTUTZ D E | 1982 | Ocean Engineering1982，9，： | 1 |
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