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| 1 | Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells显示文摘Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a new treatment modality is needed.Bcl-2 family proteins play an important role in balancing cell survival and apoptosis.The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML.ABT-199,a BH3 mimetic,was developed to target antiapoptotic protein Bcl-2.Although ABT-199 has demonstrated promising results,resistance occurs.Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2,but this is compensated by increased association of Bim with prosurvival protein Mcl-1,stabilizing Mcl-1,resulting in resistance to ABT-199.In this study,we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells.We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples.The synergistic induction of apoptosis was decreased upon Bak,Bax and Bim knockdown.While A-1210477 treatment alone also increased Mcl-1 protein levels,combination with ABT-199 reduced binding of Bim to Mcl-1.Our results demonstrate that sequestration of Bim by Mcl-1,a mechanism of ABT-199 resistance,can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477. | Daniel A Luedtke Xiaojia Niu Yihang Pan Jianyun Zhao Shuang Liu Holly Edwards Kang Chen Hai Lin Jeffrey W Taub Yubin Ge | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 11 |
| 2 | 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 |
| 3 | Regular and chaotic Bose-Einstein condensate in an accelerated Wannier-Stark lattice显示文摘 | Hai W H Lu G B Zhong H H | 2009 | Phys Rev A2009，79，05： | 1 |
| 4 | Improved mechanical behavior of bulk metallic glasses containing in situ formed ductile phase dendrite dispersions显示文摘 | Hays C C Kim C P Johnson W L | 2001 | Materials science engineering2001，，304306： | 1 |
| 5 | Discrimination and prediction of multiple beef freshness indexes based on electronic nose 显示文摘 | Xuezhen H Jun W Hai Z | 2012 | Sensors and Actuators B-Chemical2012，161，1： | 1 |
| 6 | A subma- rine navigator for the 21st century 显示文摘 | HAYS K M SCHMIDT R G WILSON W A | 2002 | IEEE Position Location and Navigation Symposium2002，，： | 1 |
| 7 | Nitrogen and phosphorus inputs control phytoplankton growth in eutrophic Lake, Taihu, China 显示文摘 | XU Hai PAERL H W QIN Bo-qiang | 2010 | Limnology and Oceanography2010，55，1： | 1 |
| 8 | 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 |
| 9 | Novel function of complement C3d as an autologous helper T-cell target显示文摘 | Knopf PM Rivera DS Hai SH McMurry J Martin W De Groot AS | | 0，，03： | 1 |
| 10 | Mosquito cathepsin B-like protease involved in embryonic degradation of vitellin is produced as a latent extraovarian precursor显示文摘 | Cho W L Tsao S M Hays A R | 1999 | J Biol Chem1999，274，13： | 1 |
| 11 | Microstructure controlled shear band pattern formation and enhanced plasticity of bulk metallic glasses containing in situ formed ductile phase dendrite dispersions显示文摘 | HAYS C C KIM C P JOHNSON W L | 2000 | Phys Rev Lett2000，84，13： | 1 |
| 12 | Clinical study of typing detection of human papillomavirus(HPV)infection with microarray from paraffin embedded specimens of cervical cancer and precursor lesions显示文摘 | Hai L Xubo W Jianxiang G | 2015 | J Nanosci Nanotechnol2015，15，9： | 1 |
| 13 | Microstructure controlled shearband pattern formation and enhanced plasticity of bulk metallicglasses containing in situ formed ductile phase dendritedispersions 显示文摘 | Hays C Kim C Johnson W | 2000 | Physical Review Letters2000，84，13： | 1 |
| 14 | Protection of multiple antioxidants Chinese herbal medicine on the oxidative stress induced by adriamycin chemotherapy显示文摘 | Qin XJ He W Hai CX | 2008 | J Appl Toxicol2008，28，3： | 1 |
| 15 | 显示文摘 | Hai Mei Mei B W | 2003 | Fuel2003，，82： | 1 |
| 16 | A new method for obtaining ultra-low sulfur diesel fuel via ultrasound assisted oxidative desulfurization显示文摘 | HAI Mei MEIL B W TEH Fu Yen | 2003 | Fuel2003，，82： | 1 |
| 17 | Effects of dietary phosphorus and calcium leVel on perfor-mance, bone mineralization and carcass characteristics of swine显示文摘 | Cromwell G L Hays V W Chaney C H | 1970 | Journal of Animal Science1970，30，： | 1 |
| 18 | Microstructure controlled shear band pattern formation and enhanced plasticityof bulk me- tallic glasses containing in situ formed ductile phase dendrite dis-persions 显示文摘 | Hays C C Kim C P Johnson W L | 2000 | Phys Rev Lett2000，84，13： | 1 |
| 19 | Nitrogen and phosphorus inputs control phytoplankton growth in eutrophic Lake Taihu,China 显示文摘 | XU Hai PAERL H W QIN Boqiang | 2010 | Limnology and Oceanography2010，55，1： | 1 |
| 20 | Treatment of Snoring and Obstructive Sleep Apnea with a Dental Orthosis 显示文摘 | Schmidt Nowara W W Meade T E Hays M B | 1991 | Chest1991，99，6： | 1 |
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