{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:52:35Z","timestamp":1785538355922,"version":"3.56.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T00:00:00Z","timestamp":1348531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Bendamustine with or without rituximab provides an effective and more tolerable alternative to the polytherapy cyclophosphamide\u2013doxorubicin\u2013vincristine\u2013prednisolone (CHOP) in the treatment of haematological tumours and is currently approved for the treatment of many haematological malignancies. Navitoclax (ABT\u2010263) is a potent inhibitor of Bcl\u20102, Bcl\u2010x<jats:sub>L<\/jats:sub> and Bcl\u2010w, which has demonstrated efficacy in haematological tumours alone and in combination with other agents. This paper describes the <jats:italic>in vivo<\/jats:italic> efficacy of combining either bendamustine or bendamustine plus rituximab (BR) with navitoclax in xenograft models of non\u2010Hodgkin's lymphoma<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Activity was tested in xenograft models of diffuse large B\u2010cell lymphoma (DoHH\u20102, SuDHL\u20104), mantle cell lymphoma (Granta 519) and Burkitt's lymphoma (RAMOS). Activity was also monitored in a systemic model of Granta 519.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Navitoclax potentiated bendamustine activity in all cell lines tested. Bendamustine activated p53 in Granta 519 tumours, concurrent with activation of caspase 3. Navitoclax also improved responses to bendamustine\u2010rituximab (BR) in a subset of tumours.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> Navitoclax in combination with bendamustine and BR is a viable combination strategy for use in the clinic and demonstrated superior efficacy compared with previously reported data for navitoclax plus CHOP and rituximab\u2010CHOP.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.02048.x","type":"journal-article","created":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T15:40:57Z","timestamp":1337874057000},"page":"881-891","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Navitoclax (ABT\u2010263) and bendamustine \u00b1 rituximab induce enhanced killing of non\u2010Hodgkin's lymphoma tumours <i>in vivo<\/i>"],"prefix":"10.1111","volume":"167","author":[{"given":"S","family":"Ackler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MJ","family":"Mitten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Clarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DC","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Schlessinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JD","family":"Leverson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ER","family":"Boghaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0268"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-009-1232-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.3947"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-176024"},{"key":"e_1_2_8_6_1","first-page":"33","article-title":"Anti\u2010CD20 antibody (IDEC\u2010C2B8, rituximab) enhances efficacy of cytotoxic drugs on neoplastic lymphocytes in vitro: role of cytokines, complement, and caspases","volume":"87","author":"Chow KU","year":"2002","journal-title":"Haematologica"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-205500"},{"key":"e_1_2_8_8_1","first-page":"1198","article-title":"Concurrent activation of MYC and BCL2 in B cell non\u2010Hodgkin lymphoma cell lines by translocation of both oncogenes to the same immunoglobulin heavy chain locus","volume":"10","author":"Dyer MJ","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/11205860-000000000-00000"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-007-0278-x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.109.060780"},{"key":"e_1_2_8_12_1","volume-title":"SEER Cancer Statistics Review, 1975\u20132009","author":"Howlader N","year":"2011"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190902943069"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0150"},{"key":"e_1_2_8_15_1","first-page":"abstr 4580","article-title":"SDX\u2010105 (TreandaTM) enhances the tumor growth inhibitory effects of rituximab in Daudi lymphoma xenografts","volume":"104","author":"Kanekal S","year":"2004","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-080325"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn076"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404776"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402168"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06899.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1061"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21433"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.151"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00873.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03579"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-130781"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm800669s"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0388"},{"key":"e_1_2_8_30_1","first-page":"abstr 405","article-title":"Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first\u2010line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany)","volume":"114","author":"Rummel MJ","year":"2009","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2005.00014.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0367"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-124487"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-199606000-00007"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.24.7837"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5836"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6093263"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2008.33.10.1265203"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1532\/IJH97.04110"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2012.02048.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1476-5381.2012.02048.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T04:24:26Z","timestamp":1697430266000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2012.02048.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,25]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1111\/j.1476-5381.2012.02048.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1476-5381.2012.02048.x","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,25]]},"assertion":[{"value":"2012-09-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}