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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 | Terminal cancer : Duration and prediction of survival time显示文摘 | Llobera J Esteva M Rifa J | 2000 | Eur J Cancer2000，36，16： | 1 |
| 3 | Effect of long-term ad- ministration of cross-sex hormone therapy on serum and urinary uric acid in transsexual persons 显示文摘 | Yahyaoui R Esteva I Haro-Mora JJ | 2008 | J Clin Endocrinol Metab2008，93，6： | 1 |
| 4 | Expression of erbB/HER recptors,hergulin and P38 in primary breast cancer using quantitative immunohistochemistry显示文摘 | Esteva FJ Hortobagyi GN Sahin AA | 2007 | Pathol Oncol Res2007，7，3： | 1 |
| 5 | Cross-talk between the ErbB/I-IER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer 显示文摘 | Jin Q Esteva FJ | 2008 | J Mammary Gland Biol Neoplasia2008，13，4： | 1 |
| 6 | Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer 显示文摘 | Jin Q Esteva FJ | 2008 | J Mammary Gland Biol Neoplasia2008，13，4： | 1 |
| 7 | Monoidal t-norm based logic:towards a logic for left-eantinuous t-norms显示文摘 | Esteva F Godo L | 2001 | Fuzzy Sets and Systems2001，124，3： | 1 |
| 8 | Chemotherapy of metastatic breast cancer: what to expect in 2001 and beyond 显示文摘 | Esteva FJ Valero V Pusztai L | 2001 | Oncologist2001，6，2： | 1 |
| 9 | The current status of docetaxel for metastatic breast cancer显示文摘 | Esteva FJ | 2002 | Oncology (Huntingt)2002，16，66： | 1 |
| 10 | On the Standard and Rational Completeness of Some Axiomatic Extensions of the Monoidal t-norm Based Logic显示文摘 | ESTEVA F GISPERT J GODO L | 2002 | Stud Logica2002，71，： | 1 |
| 11 | Monoidal t-norm based logic:towards a logic for left-continuous t-norms显示文摘 | Esteva F Godo L | 2001 | Fuzzy Sets and Systems2001，124，： | 1 |
| 12 | Monoidal t-norm based logic: Towards a logic for left-continuous t-norms 显示文摘 | Esteva F Godo L | 2001 | Fuzzy Sets and Systems2001，124，3： | 1 |
| 13 | Recombinant human erythropoietin antagonizes trastuzurnab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inacti- vation显示文摘 | Liang K Esteva F J Albarracin C | 2010 | Cancer Ce112010，18，5： | 1 |
| 14 | Serum HER-2/neu change predicts clinical outcome to trastuzumab-based therapy显示文摘 | Ali SM Esteva FJ Fornier M | | 0，，18： | 1 |
| 15 | Cross-talk between the ErbB/HER fam ily and the type I insulin-like growth factor recep tor sig naling pathway in breast cancer显示文摘 | Jin Q Esteva FJ | 2008 | J Mammary Gland Bi ol Neop lasia2008，13，4： | 1 |
| 16 | Omeprazole does not in terfere with the antiplatelet effect of low2does aspirin in man显示文摘 | Inarrea P Esteva F Comudella R | 2000 | Stand J Gastroenterol2000，3，35： | 1 |
| 17 | PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients显示文摘 | Yoichi Nagata Keng-Hsueh Lan Xiaoyan Zhou Ming Tan Francisco J. Esteva Aysegul A. Sahin Kristine S. Klos Ping Li Brett P. Monia Nina T. Nguyen Gabriel N. Hortobagyi Mien-Chie Hung Dihua Yu | 2004 | Cancer Cell2004，，2： | 1 |
| 18 | PTEN,PIK3CA,p-AKT,and p-p70S6K status:association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer显示文摘 | Esteva F J Guo H Zhang S | | 0，，04： | 1 |
| 19 | The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells显示文摘 | Nahta R Hung MC Esteva FJ | 2004 | Cancer Res2004，64，7： | 1 |
| 20 | Trastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer显示文摘 | Esteva FJ Seidman AD | 2000 | Semin Oncol2000，27，611： | 1 |
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