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Blood, 1 January 2005, Vol. 105, No. 1, pp. 350-357. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2004-06-2499. This Article Full Text (PDF) All Versions of this Article: 2004-06-2499v1 105/1/350    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lin, B. Articles by Anderson, K. C Search for Related Content PubMed PubMed Citation Articles by Lin, B. Articles by Anderson, K. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 1, 2004 Accepted August 21, 2004 Patupilone (Epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo Boris Lin, Laurence Catley, Richard LeBlanc, Constantine Mitsiades, Renate Burger, Yu-Tzu Tai, Klaus Podar, Markus Wartmann, Dharminder Chauhan, James D Griffin, and Kenneth C Anderson* Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, and the Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Oncology Research, Novartis Institutes for BioMedical Research, Basel, Switzerland * Corresponding author; email: Kenneth_Anderson{at}dfci.harvard.edu. In this study, we investigated the in vitro and in vivo efficacy of patupilone (epothilone B, EPO906), a novel non-taxane microtubule stabilizing agent, in treatment of multiple myeloma (MM). Patupilone directly inhibited growth and survival of MM cells, including those resistant to conventional chemotherapies, such as the taxane paclitaxel. Patupilone induced G2M arrest of MM cells, with subsequent apoptosis. Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1), two known growth and survival factors for MM, did not protect MM.1S cells against patupilone-induced cell death. Proliferation of MM cells induced by adherence to bone marrow stromal cells (BMSCs) was also inhibited by patupilone, and was paralleled by down-regulation of vascular endothelial growth factor (VEGF) secretion. Importantly, stimulation of MM patient cells, either with IL-6 or by adherence to BMSCs, enhanced the anti-proliferative and pro-apoptotic effects of patupilone. Moreover, patupilone was effective against MM cell lines that overexpress the MDR1/P-glycoprotein multi-drug efflux pump. In addition, patupilone was effective in slowing tumor growth and prolonging median survival of mice orthotopically transplanted with MM tumor cells. Taken together, these pre-clinical findings suggest that patupilone may be a safe and effective drug in the treatment of MM, providing the framework for clinical studies to improve patient outcome in MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. G. Morris and M. N. Fornier Microtubule Active Agents: Beyond the Taxane Frontier Clin. Cancer Res., November 15, 2008; 14(22): 7167 - 7172. [Abstract] [Full Text] [PDF] T. Hideshima, D. Chauhan, P. Richardson, and K. C. Anderson Identification and Validation of Novel Therapeutic Targets for Multiple Myeloma J. Clin. Oncol., September 10, 2005; 23(26): 6345 - 6350. [Abstract] [Full Text] [PDF] K.-D. Wu, Y. S. Cho, J. Katz, V. Ponomarev, S. Chen-Kiang, S. J. Danishefsky, and M. A. S. Moore Investigation of antitumor effects of synthetic epothilone analogs in human myeloma models in vitro and in vivo PNAS, July 26, 2005; 102(30): 10640 - 10645. [Abstract] [Full Text] [PDF]

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