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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 | Inhibition of CDK9 by voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia显示文摘Venetoclax,an FDA-approved Bcl-2 selective inhibitor for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia(AML),is tolerated well in elderly patients with AML and has good overall response rates;however,resistance remains a concern.In this study,we show that targeting CDK9 with voruciclib in combination with venetoclax results in synergistic antileukemic activity against AML cell lines and primary patient samples.CDK9 inhibition enhances venetoclax activity through downregulation of Mcl-1 and c-Myc.However,downregulation of Mcl-1 is transient,which necessitates an intermittent treatment schedule to allow for repeated downregulation of Mcl-1.Accordingly,an every other day schedule of the CDK9 inhibitor is effective in vitro and in vivo in enhancing the efficacy of venetoclax.Our preclinical data provide a rationale for an intermittent drug administration schedule for the clinical evaluation of the combination treatment for AML. | Daniel A.Luedtke Yongwei Su Jun Ma Xinyu Li Steven ABuck Holly Edwards Lisa Polin Juiwanna Kushner Sijana HDzinic Kathryn White Hai Lin Jeffrey WTaub Yubin Ge | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
| 3 | Sterioid assays and preovalatoty follicular development in human ovaries primed with gonadotropins显示文摘 | Edwards TG Stetoe PC Abraham GE | 1972 | Lancet1972，2，7778： | 1 |
| 4 | Incidence and evolution of inferior alveolar nerve lesions following lower third molar extraction 显示文摘 | Elena GE Edward VC Leonardo BA | 2005 | Oral Surg Oral Med Oral Pathol Oral Radiol Endod2005，99，： | 1 |
| 5 | Long term exposure to enhanced UV-B radiation is not detri- mental to growth and photosynthesis in Douglas-fir 显示文摘 | BASSMAN JH EDWARD GE ROB- BERECHT R | 2002 | New Phytologist2002，154，1： | 1 |
| 6 | Hereditary hypoc eruloplasminemia显示文摘 | Edwards CQ Williams DM Cartwright GE | 1979 | Clin Genet1979，15，4： | 1 |
| 7 | On attempts at cloning in the human显示文摘 | Jones HW Edward RG Seidel GE | 1993 | Fertil Steril1993，61，42： | 1 |
| 8 | Covered stent exclusion of blunt traumatic carotid artery pseudoaneurysm: case report and review of the literature显示文摘 | Fusonie GE Edwards JD Reed AB | 2004 | Ann Vasc Surg2004，18，： | 1 |
| 9 | Chronic pain after inguinal hemiorrhaphy显示文摘 | Ferzli GS Edwards ED Khoury GE | 2007 | J Am Coil Surg2007，205，2： | 1 |
| 10 | Covered stent exclusion of blunt traumatic carotid artery pseudoaneurysm: case report and review of the literature 显示文摘 | Fusonie GE Edwards JD Reed AB | 2004 | Ann Vase Surg2004，18，3： | 1 |
| 11 | Bioreductive drugs as post-irradiation sensitizers: comparison of dual function agents with SR 4233 and the mitomycin C analogue EO9显示文摘 | Adams GE Stratford IJ Edwards HS | 1992 | Int J Radiat Oncol Biol Phys1992，22，4： | 1 |
| 12 | Influence of pesticide application on pest and predatory arthropeds assoaiated with transgenic Bt cotton and non-transgenic cotton plants 显示文摘 | Men X Y Ge F Edwards C A Yardim E N | 2004 | Entomology Phytoparasitica2004，32，3： | 1 |
| 13 | Analysis of inhibition of photosynthesis due to water stress in the C3 species Hordeum vulgate and Vicia faba:electron transport,CO2 fixation and carboxylation capacity显示文摘 | Lal AM Ku SB Edwards GE | 1996 | Photosynthesis Research1996，49，： | 1 |
| 14 | A Conceptual Pathways Model to Promote Positive YouthDevelopment in Children Raised by Their Grandparents 显示文摘 | OW Edwards GE Taub | 2009 | School Psychology Quarterly2009，24，3： | 1 |
| 15 | Cardiomyopathy in transgenis myfs mice 显示文摘 | Lyons GE Micales BK | 1996 | Cire Res1996，78，3： | 1 |
| 16 | Chronic Pain after Inguinal Hemiorrhaphy 显示文摘 | Ferzli GS Edwards ED Khoury GE | 2007 | J Am Coll surg2007，205，2： | 1 |
| 17 | Analysis of inhibition of photosynthesis under water stress in the C4 species Amaranthuscruentus and Zea mays: electron transport, CO2 fixation and carboxylation capacity 显示文摘 | Lal A Edwards GE | 1996 | Austr J Plant Physiol1996，23，4： | 1 |
| 18 | Relationship between photosystem Ⅱ activity and CO2 fixation in leaves显示文摘 | Krall JP Edwards GE 1992 | 1992 | Physiol Plantarum1992，86，： | 1 |
| 19 | Transdermal lovastatinenhances fracture repair in rats显示文摘 | Gutierrez GE Edwards JR Garretti IR | 2008 | J Bone Miner Res2008，23，11： | 1 |
| 20 | A conceptual pathways model to promotepositive youth development in children raised by their grandparents显示文摘 | EDWARDS 0W TAUB GE | 2009 | Sch Psychol Q2009，24，3： | 1 |
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