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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 | Pectic acids in the production of wood-containing paper显示文摘 | Kenneth E S Anna C S Jeffrey W T | 1998 | TAPPI J1998，81，7： | 1 |
| 3 | Reversal of P-glycoprotein (P-gp) mediated multidrug resistance in colon cancer cells by cryptotanshinone and dihydrotanshinone of salvia miltiorrhiza 显示文摘 | TAO H KENNETH K W T LIN Z | 2014 | Phytomed Inter J Phytother Phytopharmacol2014，21，11： | 1 |
| 4 | Platinum-based anticancer agents:innovative design strategies and biological perspectives显示文摘 | YEE-PING H STEVE C F A-Y KENNETH K W T | 2003 | Med Res Rev2003，23，5： | 1 |
| 5 | Social cognition in cynical hostility显示文摘 | KENNETH D SMITH T W | | 0，，05： | 1 |
| 6 | Platinum-based anticancer agents:innovative design strategies and biological perspectives显示文摘 | YEE-PING H STEVE C F A-Y KENNETH K W T | 2003 | Med Res Rev2003，23，5： | 1 |
| 7 | HaPten Induced Model of Murine Inflam-matory Bowel Disease显示文摘 | Kenneth W Beagley Almaz T Sharmanove | 1996 | The Journal of Immunology1996，157，： | 1 |
| 8 | Pectic acids in the production of wood-containing paper显示文摘 | Kenneth E Sundberg K Jeffrey W T | 1998 | Tappi J1998，81，7： | 1 |
| 9 | Pectin acids in the Production of wood containing paper显示文摘 | Anna C Sundberg Jeffrey W T | 1998 | Tappi1998，81，7： | 1 |
| 10 | Poly (ethylenimine) and its role in gene delivery 显示文摘 | GODBEY W T WU KENNETH K MIKOS ANTONIOS G | 1999 | Journal of Controlled Release1999，60，： | 1 |
| 11 | Use of Wound-Pro- tection System and Postoperative Wound-Infection Rates in Open Appendee-tomy: A Randomized Prospective Trial显示文摘 | Pamela L Kenneth W Benedict T | 2009 | Arch Surg2009，144，9： | 1 |
| 12 | Platinum-based anticancer agents:innovarive design strategies and biological perspectives显示文摘 | HO Y P AU-YEUNG S C F KENNETH K W T | 2003 | Med Res Rev2003，23，5： | 1 |
| 13 | Obstructive sleep apnea is independently asscociated with insulin resistance 显示文摘 | Mary S M Malthew M T Kenneth W T | 2002 | Am J Respir Crit Care Med2002，165，5： | 1 |
| 14 | 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 |
| 15 | Brief develop- ment of underwater autonomous biomimetie fish显示文摘 | Beng Yeo K Kenneth T K T Loong W W | 2014 | Jour- nal of Applied Sciences2014，14，23： | 1 |
| 16 | Pectin acids in the production of wood containing paper显示文摘 | Kenneth E Sundberg Anna C Sundberg Jeffrey W T | 1998 | Tappl1998，81，7： | 1 |
| 17 | Use of Wound-Pro-tectionSystem and Postperative Wound-Infection Rates in Open Appendec-tomy:A Randomized Prospective Trial显示文摘 | Pamela L Kenneth W Benedict T | 2009 | Arch Surg2009，144，9： | 1 |
| 18 | Synthesis,transition temperatures,and optical properties of various 2,6-disubstituted naphthalenes and related 1-benzothiophenes with butylsulfanyl and cyano or isothiocyanato terminal groups显示文摘 | Alexander J S Kenneth J T John W G | 2000 | Journal of Materials Chemistry2000，10，9： | 1 |
| 19 | Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantion in sheep 显示文摘 | KENNETH W LIECHTY AIMEN T C | 2000 | Nat Med2000，6，11： | 1 |
| 20 | Pectic acids in the production of wood containing paper显示文摘 | Kenneth E Sundberg Anna C Sundberg Jeffrey W T | 1998 | Tappi J1998，81，7： | 1 |
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