SEARCH:   Advanced

Blood, 15 July 2005, Vol. 106, No. 2, pp. 706-712. Prepublished online as a Blood First Edition Paper on March 31, 2005; DOI 10.1182/blood-2005-02-0838. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-02-0838v1 106/2/706    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 Yasui, H. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Yasui, H. Articles by Anderson, K. C. Related Collections Neoplasia Apoptosis Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma Hiroshi Yasui, Teru Hideshima, Makoto Hamasaki, Aldo M. Roccaro, Norihiko Shiraishi, Shaji Kumar, Pierfrancesco Tassone, Kenji Ishitsuka, Noopur Raje, Yu-Tzu Tai, Klaus Podar, Dharminder Chauhan, Lorenzo M. Leoni, Sarath Kanekal, Gary Elliott, Nikhil C. Munshi, and Kenneth C. Anderson From the Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Salmedix, Inc, San Diego, CA; and the First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan. In this study we report that R-etodolac (SDX-101), at clinically relevant concentrations, induces potent cytotoxicity in drug-sensitive multiple myeloma (MM) cell lines, as well as in dexamethasone (MM.1R)-, doxorubicin (Dox40/RPMI8226)-, and bortezomib (DHL4)-resistant cell lines. Immunoblot analysis demonstrates that R-etodolac induces apoptosis characterized by caspase-8, -9, and -3 and PARP (poly-ADP [adenosine diphosphate]-ribose polymerase) cleavage and down-regulation of cyclin D1 expression. Subcytotoxic doses of R-etodolac up-regulate myeloid cell leukemia-1 proapoptotic variant (Mcl-1S), while enhancing dexamethasone (Dex)-induced caspase activation and apoptosis. The combination of R-etodolac with Dex results in a highly synergistic cytotoxic effect. R-etodolac also induces apoptosis against primary cells isolated from patients with MM refractory to chemotherapy. Although interleukin 6 (IL-6) and insulin-like growth factor-1 (IGF-1) abrogate Dex-induced MM cell cytotoxicity, neither IL-6 nor IGF-1 protects against R-etodolac-induced cytotoxicity in MM cells. R-etodolac also inhibits viability of MM cells adherent to bone marrow stromal cells (BMSCs), thereby overcoming a mechanism of drug resistance commonly observed with other conventional chemotherapeutic agents. Our data, therefore, indicate that R-etodolac circumvents drug resistance in MM cells at clinically relevant concentrations, targets Mcl-1, and can be synergistically combined with Dex. (Blood. 2005;106:706-712) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: New aspects of myeloma management Angelo Vacca Blood 2005 106: 395. [Full Text] [PDF] This article has been cited by other articles: M. Nojima, R. Maruyama, H. Yasui, H. Suzuki, Y. Maruyama, I. Tarasawa, Y. Sasaki, H. Asaoku, H. Sakai, T. Hayashi, et al. Genomic Screening for Genes Silenced by DNA Methylation Revealed an Association between RASD1 Inactivation and Dexamethasone Resistance in Multiple Myeloma Clin. Cancer Res., July 1, 2009; 15(13): 4356 - 4364. [Abstract] [Full Text] [PDF] H. Ikeda, T. Hideshima, M. Fulciniti, R. J. Lutz, H. Yasui, Y. Okawa, T. Kiziltepe, S. Vallet, S. Pozzi, L. Santo, et al. The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Selective Cytotoxicity Against CD138-Positive Multiple Myeloma Cells In vitro and In vivo Clin. Cancer Res., June 15, 2009; 15(12): 4028 - 4037. [Abstract] [Full Text] [PDF] M. Liedtke and M. L. Cleary Therapeutic targeting of MLL Blood, June 11, 2009; 113(24): 6061 - 6068. [Abstract] [Full Text] [PDF] B. Barlogie, G. Tricot, J. Haessler, F. van Rhee, M. Cottler-Fox, E. Anaissie, J. Waldron, M. Pineda-Roman, R. Thertulien, M. Zangari, et al. Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3000 patients treated since 1989 Blood, January 1, 2008; 111(1): 94 - 100. [Abstract] [Full Text] [PDF] R. Feng, G. Anderson, G. Xiao, G. Elliott, L. Leoni, M. Y. Mapara, G. D. Roodman, and S. Lentzsch SDX-308, a nonsteroidal anti-inflammatory agent, inhibits NF-{kappa}B activity, resulting in strong inhibition of osteoclast formation/activity and multiple myeloma cell growth Blood, March 1, 2007; 109(5): 2130 - 2138. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020