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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 | Activating transcription factor 3,astress-inducible gene,suppresses ras-stimulated tumorigenesis显示文摘 | LU D WOLFGANG C D HAI T | 2006 | Biol Chem2006，281，10： | 1 |
| 3 | Positive solutions to a class of elliptic poundary value problems显示文摘 | HAI D D | 1998 | JMath Anal Appl1998，217，2： | 1 |
| 4 | Polycyelic aromatic hydrocarbon size distributions in aerosols from appliances of residential wood combustion as determined by direct thermal desorption-GC/MS显示文摘 | Hays M D Smith N D Kinsey J | | 0，，08： | 1 |
| 5 | Age dating and the orbital theory of the ice ages: development of a high-reso- lution 0 to 300000-year chronostratigraphy显示文摘 | Martinson D G Pisias N G Hays J D | 1987 | Quaternary Research1987，27，1： | 1 |
| 6 | Effects of nitrogen and phosphorus on blue grama growth and mycorrhizal infection 显示文摘 | Hays R Reid C C P John T V St Coleman D C | 1982 | Oecologia1982，54，： | 1 |
| 7 | Detection of Eperythozoon suis using the polymerase chain reaction显示文摘 | Gwaltney S M Hays M P Oberst R D | 1993 | J Vet Diagn Invest1993，，5： | 1 |
| 8 | A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain显示文摘 | Sloan Pa Moulin D E Hays H | 1998 | J Pain Symptom Manage1998，16，2： | 1 |
| 9 | Two-channel direction-detection Doppler lidar employing a charge -coupled device as a detector显示文摘 | IRGANG T D HAYS P B SKINNER W R | 2002 | Appl Opt2002，41，6： | 1 |
| 10 | Open burning of agricultural biomass: Physical and chemical properties of particle-phase emissions显示文摘 | Hays M D Fine P M Geron C D | 2005 | Atmospheric Environment2005，39，36： | 1 |
| 11 | Artemisinin pharmacokinetics and efficacy in uncomplicated-malaria patients treated with two different dosage regimens显示文摘 | Gordi T Huong D X Hai T N | | 0，，04： | 1 |
| 12 | Experimental infections and natural outbreaks of Eperythozoonosis in pigs identified by PCR-DNA hybridizations显示文摘 | Oberst R D Gwaltney S M Hays M P | 1993 | J Vet Diagn Invest1993，，5： | 1 |
| 13 | Detection of Eperythrozoonsuis using the PCR 显示文摘 | Gwaltney S M Hays M P Oberst R D | 1993 | J Vet Diagn Invest1993，5，1： | 1 |
| 14 | Detection of Eperythrozoon suis using the polymerase chain reaction显示文摘 | Gwaltney S M Hays M P Oberst R D | 1993 | J Vet Diagn Invest1993，5，1： | 1 |
| 15 | Age dating and the orbital theory of the ice ages: development of a high-resolution 0 -300, 000years显示文摘 | Martinson D G Pisias N G Hays J D | 1987 | QuaternaryResearch1987，27，： | 1 |
| 16 | Cycladophora davisiana:A stratigraphic tool for Pleistocence North Atlantic and interhemispheric correlation显示文摘 | MorleyJ J Hays J D | 1979 | Earth Planetary Science Letter1979，44，： | 1 |
| 17 | Existence Results for Superlinear Semi-positone BVP's显示文摘 | Anuradha V Hai D D Shivaji R | 1996 | Proc Amer Soc1996，124，： | 1 |
| 18 | Age dating and orbital theory of the ice ages : Development of a high res- olution 0 - 300,000 years chronostratigraphy 显示文摘 | MARTINSON D PISIAS N HAYS J D | 1987 | Qua- ternary Research1987，27，： | 1 |
| 19 | Developing process for coating copper particles with silver by electroless plating method 显示文摘 | HAI H T AHN J Q KIM D J | 2006 | Surf Coat Technol2006，201，6： | 1 |
| 20 | Influ- enza viruses expressing chimeric hemagglutinins: Globu- lar head and stalk domains derived from different sub- types 显示文摘 | Hai R Krammer F Tan G S Pica N Eggink D Maamary J Margine I Albrecht R A Palese P | 2012 | J Virol2012，86，10： | 1 |
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