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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 | Structure-property relations in processing high-performance polyisoimide-imide resins显示文摘 | CHOW A W HAMLIN R D LANDIS A L | 1992 | Journal of Rheology1992，36，8： | 1 |
| 3 | Design Considerations and a Suggested Approach for Regional and Comparative Ecological Risk Assessment显示文摘 | Landis W G Wiegers J A | 1997 | Human and Ecolog- ical Risk Assessment1997，3，3： | 1 |
| 4 | A Regional Multiple Stressor Risk Assessment of the Codorus Creek Watershed Applying the Relative Risk Model显示文摘 | Obery A M Landis W G | 2002 | Human and Ecological Risk Assessment2002，8，： | 1 |
| 5 | Design considerations and a suggested approach for regional and comparative ecological risk assessment显示文摘 | LANDIS W G WIEGERS J A | 1997 | Human and Ecological Risk Assessment1997，3，3： | 1 |
| 6 | The frontier in ecological risk assessment at expanding spatial and temporal scales 显示文摘 | LANDIS W G | 2003 | Human and Ecological Risk Assessment2003，9，6： | 1 |
| 7 | Modeling the Roadside Walking Environment: A Pedestrian level of Service显示文摘 | Landis B W VattikutiV R Otten berg R M McLeod D S Guttenplan M | | Transportation Research Record: Journal of the Transportation Research Board 200 I 17730，，： | 1 |
| 8 | Twenty years before and hence; ecological risk assessment at multiple scales with multiple stressors and multiple endpoints 显示文摘 | LANDIS W G | 2003 | Human and Ecological Risk Assessment2003，9，5： | 1 |
| 9 | Level-of-service model for pedestrians at signalized intersections显示文摘 | Theodore A Petritsch Bruce W Landis Peyton S McLeod | 2005 | Journal of Transportation Research Board2005，，1： | 1 |
| 10 | Regional risk assessment of a Brazilian rain forest reserve 显示文摘 | MOARES R LANDIS W G MOLANDER S | 2002 | Human and Ecological Risk Assessments2002，8，7： | 1 |
| 11 | Level-of-service model for pedestrians at signalized intersections显示文摘 | Petritsch T A Landis B W Mcleod P S | 2005 | Transportation Research Record2005，，1939： | 1 |
| 12 | Design considerations and a suggested approach for regional and comparative ecological risk assessment显示文摘 | LANDIS W G WIEGERS J A | 1997 | Human and Ecological Risk Assessment1997，3，3： | 1 |
| 13 | Undecidability of static analysis 显示文摘 | LANDI W | 1992 | ACM Letters on Programming Languages and Systems1992，1，4： | 1 |
| 14 | The layered and historical nature of ecological systems and the risk assessment ofpesticides显示文摘 | Landis W G Matthews R A Matthews G B | 1996 | Environ Toxicol Chem1996，15，： | 1 |
| 15 | The community conditioning hypothesis and its application to environmentaltoxicology显示文摘 | Matthews R A Landis W G Matthews G B | 1996 | Environ Toxicol Chem1996，15，： | 1 |
| 16 | Design considerations and suggested approach for regional and comparative ecological risk assessment显示文摘 | LANDIS W G WIEGERS J A | 1997 | Human Ecology and Risk Assessment1997，3，： | 1 |
| 17 | Perfect metamaterial absorber显示文摘 | Landy N I Sajuyigbe S Mock J J Smith D R Padilla W J | 2008 | Physical Review Letters2008，100，20： | 1 |
| 18 | Regional ecological risk assess- ment of a near shore marine environment : Cherry Point, WA 显示文摘 | EMILY H H LANDIS W G | 2004 | Human and Ecological Risk Assessment2004，10，： | 1 |
| 19 | The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix 显示文摘 | Landis W J | 1995 | Bone1995，16，5： | 1 |
| 20 | Undecidability of static analysis 显示文摘 | LANDI W | 1992 | ACM Letters on Programming Languages and Systems1992，1，4： | 1 |
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