{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:31:18Z","timestamp":1791228678586,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Leukemia Research"],"published-print":{"date-parts":[[2012,7]]},"DOI":"10.1016\/j.leukres.2012.02.010","type":"journal-article","created":{"date-parts":[[2012,5,5]],"date-time":"2012-05-05T10:38:10Z","timestamp":1336214290000},"page":"912-920","source":"Crossref","is-referenced-by-count":38,"title":["The dual PI3K and mTOR inhibitor NVP-BEZ235 exhibits anti-proliferative activity and overcomes bortezomib resistance in mantle cell lymphoma cells"],"prefix":"10.1016","volume":"36","author":[{"given":"Areumnuri","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhoo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Eun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Suk","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Joo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Sook","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.leukres.2012.02.010_bib0005","first-page":"115","article-title":"Mantle-cell lymphoma","volume":"36","author":"Campo","year":"1999","journal-title":"Semin Hematol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0010","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/(SICI)1097-0142(19980201)82:3<567::AID-CNCR20>3.0.CO;2-Z","article-title":"Mantle cell lymphoma: presenting features, response to therapy, and prognostic factors","volume":"82","author":"Bosch","year":"1998","journal-title":"Cancer"},{"key":"10.1016\/j.leukres.2012.02.010_bib0015","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1182\/blood.V89.6.2067","article-title":"Mantle cell lymphoma: a clinicopathologic study of 80 cases","volume":"89","author":"Argatoff","year":"1997","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0020","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1046\/j.1365-2141.2003.04761.x","article-title":"Molecular basis of mantle cell lymphoma","volume":"124","author":"Bertoni","year":"2004","journal-title":"Br J Haematol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0025","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1182\/blood-2006-04-015586","article-title":"Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma","volume":"108","author":"Rudelius","year":"2006","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0030","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1182\/blood-2008-10-183467","article-title":"BAFF-R promotes cell proliferation and survival through interaction with IKKbeta and NF-kappaB\/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells","volume":"113","author":"Fu","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0035","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1182\/blood-2007-02-068791","article-title":"Functionally associated targets in mantle cell lymphoma as defined by DNA microarrays and RNA interference","volume":"111","author":"Ortega-Paino","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0040","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1074\/mcp.M800515-MCP200","article-title":"Protein profiling of plasma membranes defines aberrant signaling pathways in mantle cell lymphoma","volume":"8","author":"Boyd","year":"2009","journal-title":"Mol Cell Proteomics"},{"key":"10.1016\/j.leukres.2012.02.010_bib0045","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1158\/1078-0432.CCR-07-0871","article-title":"Bortezomib for the treatment of mantle cell lymphoma","volume":"13","author":"Kane","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.leukres.2012.02.010_bib0050","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1200\/JCO.2005.02.050","article-title":"Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin\u2019 lymphoma and mantle cell lymphoma","volume":"23","author":"O\u2019Connor","year":"2005","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0055","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1200\/JCO.2005.03.108","article-title":"Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma","volume":"23","author":"Goy","year":"2005","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0060","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/annonc\/mdn656","article-title":"Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study","volume":"20","author":"Goy","year":"2009","journal-title":"Ann Oncol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0065","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/nrc2664","article-title":"Targeting PI3K signalling in cancer: opportunities, challenges and limitations","volume":"9","author":"Engelman","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.leukres.2012.02.010_bib0070","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1182\/blood-2007-07-103481","article-title":"Distinct functional significance of Akt and mTOR constitutive activation in mantle cell lymphoma","volume":"111","author":"Dal Col","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0075","doi-asserted-by":"crossref","first-page":"17479","DOI":"10.1074\/jbc.C000880200","article-title":"Akt participation in the Wnt signaling pathway through Dishevelled","volume":"276","author":"Fukumoto","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.leukres.2012.02.010_bib0080","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1182\/blood-2009-08-237537","article-title":"Rituximab inhibits B-cell receptor signaling","volume":"115","author":"Kheirallah","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0085","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0092-8674(02)00833-4","article-title":"Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action","volume":"110","author":"Hara","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.leukres.2012.02.010_bib0090","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","article-title":"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton","volume":"14","author":"Sarbassov","year":"2004","journal-title":"Curr Biol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0095","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nrm1018","article-title":"Tor signalling in bugs, brain and brawn","volume":"4","author":"Jacinto","year":"2003","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0100","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.coph.2008.08.004","article-title":"Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises","volume":"8","author":"Yap","year":"2008","journal-title":"Curr Opin Pharmacol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0105","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1158\/0008-5472.CAN-05-2925","article-title":"mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt","volume":"66","author":"O\u2019Reilly","year":"2006","journal-title":"Cancer Res"},{"key":"10.1016\/j.leukres.2012.02.010_bib0110","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.yexcr.2008.11.007","article-title":"The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma","volume":"315","author":"Baumann","year":"2009","journal-title":"Exp Cell Res"},{"key":"10.1016\/j.leukres.2012.02.010_bib0115","doi-asserted-by":"crossref","first-page":"8097","DOI":"10.1158\/0008-5472.CAN-10-1814","article-title":"Activity of the novel dual phosphatidylinositol 3-kinase\/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia","volume":"70","author":"Chiarini","year":"2010","journal-title":"Cancer Res"},{"key":"10.1016\/j.leukres.2012.02.010_bib0120","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/leu.2010.154","article-title":"The dual PI3K\/mTOR inhibitor, NVP-BEZ235, is efficacious against follicular lymphoma","volume":"24","author":"Bhende","year":"2010","journal-title":"Leukemia"},{"key":"10.1016\/j.leukres.2012.02.010_bib0125","first-page":"849","article-title":"The dual PI3K\/mTOR inhibitor BEZ235 is effective in lung cancer cell lines","volume":"31","author":"Herrera","year":"2011","journal-title":"Anticancer Res"},{"key":"10.1016\/j.leukres.2012.02.010_bib0130","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1158\/1535-7163.MCT-08-0017","article-title":"Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase\/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity","volume":"7","author":"Maira","year":"2008","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.leukres.2012.02.010_bib0135","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1074\/jbc.M309999200","article-title":"AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression","volume":"279","author":"Gera","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.leukres.2012.02.010_bib0140","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.critrevonc.2005.10.001","article-title":"Treatment of mantle cell lymphoma: current approach and future directions","volume":"58","author":"Brody","year":"2006","journal-title":"Crit Rev Oncol Hematol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0145","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/nrc2230","article-title":"Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics","volume":"7","author":"Jares","year":"2007","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.leukres.2012.02.010_bib0150","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1200\/JCO.2005.04.164","article-title":"Effect of single-agent rituximab given at the standard schedule or as prolonged treatment in patients with mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research (SAKK)","volume":"23","author":"Ghielmini","year":"2005","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0155","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1200\/JCO.2006.07.9665","article-title":"Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma","volume":"24","author":"Fisher","year":"2006","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0160","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1158\/1078-0432.CCR-07-1372","article-title":"A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies","volume":"14","author":"Rizzieri","year":"2008","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.leukres.2012.02.010_bib0165","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/j.1365-2141.2009.07626.x","article-title":"Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma","volume":"145","author":"Habermann","year":"2009","journal-title":"Br J Haematol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0170","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1200\/JCO.20.5.1288","article-title":"Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival","volume":"20","author":"Howard","year":"2002","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0175","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2004.12.030","article-title":"Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function","volume":"17","author":"Chen","year":"2005","journal-title":"Mol Cell"},{"key":"10.1016\/j.leukres.2012.02.010_bib0180","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1182\/blood-2007-08-104950","article-title":"Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein","volume":"112","author":"Oerlemans","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0185","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1365-2141.2006.06132.x","article-title":"Gene expression analysis of B-lymphoma cells resistant and sensitive to bortezomib","volume":"134","author":"Shringarpure","year":"2006","journal-title":"Br J Haematol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0190","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1158\/1535-7163.MCT-05-0068","article-title":"Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor\/insulin receptor substrate-1\/phosphatidylinositol 3-kinase cascade","volume":"4","author":"Shi","year":"2005","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.leukres.2012.02.010_bib0195","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1182\/blood-2004-10-3999","article-title":"Proteomic analysis of mantle-cell lymphoma by protein microarray","volume":"105","author":"Ghobrial","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.leukres.2012.02.010_bib0200","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/j.1365-2141.2005.05630.x","article-title":"Gene expression profiling of mantle cell lymphoma cells reveals aberrant expression of genes from the PI3K-AKT, WNT and TGFbeta signalling pathways","volume":"130","author":"Rizzatti","year":"2005","journal-title":"Br J Haematol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0205","doi-asserted-by":"crossref","first-page":"5724","DOI":"10.1158\/1078-0432.CCR-08-3215","article-title":"Phosphatidylinositol 3\u2032-kinase catalytic subunit alpha gene amplification contributes to the pathogenesis of mantle cell lymphoma","volume":"15","author":"Psyrri","year":"2009","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.leukres.2012.02.010_bib0210","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/onc.2008.502","article-title":"Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells","volume":"28","author":"Prasad","year":"2009","journal-title":"Oncogene"},{"key":"10.1016\/j.leukres.2012.02.010_bib0215","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11912-009-0016-4","article-title":"Perifosine: update on a novel Akt inhibitor","volume":"11","author":"Gills","year":"2009","journal-title":"Curr Oncol Rep"},{"key":"10.1016\/j.leukres.2012.02.010_bib0220","first-page":"169","article-title":"mTOR signaling to translation","volume":"279","author":"Gingras","year":"2004","journal-title":"Curr Top Microbiol Immunol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0225","doi-asserted-by":"crossref","first-page":"5347","DOI":"10.1200\/JCO.2005.13.466","article-title":"Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma","volume":"23","author":"Witzig","year":"2005","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.leukres.2012.02.010_bib0230","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S1097-2765(02)00636-6","article-title":"Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control","volume":"10","author":"Loewith","year":"2002","journal-title":"Mol Cell"}],"container-title":["Leukemia Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0145212612000562?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0145212612000562?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T04:33:55Z","timestamp":1594096435000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0145212612000562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7]]},"references-count":46,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["S0145212612000562"],"URL":"https:\/\/doi.org\/10.1016\/j.leukres.2012.02.010","relation":{},"ISSN":["0145-2126"],"issn-type":[{"value":"0145-2126","type":"print"}],"subject":[],"published":{"date-parts":[[2012,7]]}}}