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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 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 Citation Map 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. Related Collections Neoplasia Cytoskeleton Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 From the Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA; the Department of Medicine, Harvard Medical School, Boston, MA; and the Novartis Institutes for BioMedical Research, Oncology Research, Basel, Switzerland. In this study, we investigated the in vitro and in vivo efficacy of patupilone (epothilone B, EPO906), a novel nontaxane 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), 2 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 cells from patients with MM, either with IL-6 or by adherence to BMSCs, enhanced the anti-proliferative and proapoptotic effects of patupilone. Moreover, patupilone was effective against MM cell lines that overexpress the MDR1/P-glycoprotein multidrug efflux pump. In addition, patupilone was effective in slowing tumor growth and prolonging median survival of mice that received orthotopical transplants with MM tumor cells. Taken together, these preclinical 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. (Blood. 2005;105:350-357) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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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