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This Article Full Text Full Text (PDF) 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 Hideshima, T. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Hideshima, T. Articles by Anderson, K. C. Related Collections Neoplasia Plenary Papers Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2000, Vol. 96, No. 9, pp. 2943-2950 PLENARY PAPER Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy Teru Hideshima, Dharminder Chauhan, Yoshihito Shima, Noopur Raje, Faith E. Davies, Yu-Tzu Tai, Steven P. Treon, Boris Lin, Robert L. Schlossman, Paul Richardson, George Muller, David I. Stirling, and Kenneth C. Anderson From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ. Although thalidomide (Thal) was initially used to treat multiple myeloma (MM) because of its known antiangiogenic effects, the mechanism of its anti-MM activity is unclear. These studies demonstrate clinical activity of Thal against MM that is refractory to conventional therapy and delineate mechanisms of anti-tumor activity of Thal and its potent analogs (immunomodulatory drugs [IMiDs]). Importantly, these agents act directly, by inducing apoptosis or G1 growth arrest, in MM cell lines and in patient MM cells that are resistant to melphalan, doxorubicin, and dexamethasone (Dex). Moreover, Thal and the IMiDs enhance the anti-MM activity of Dex and, conversely, are inhibited by interleukin 6. As for Dex, apoptotic signaling triggered by Thal and the IMiDs is associated with activation of related adhesion focal tyrosine kinase. These studies establish the framework for the development and testing of Thal and the IMiDs in a new treatment paradigm to target both the tumor cell and the microenvironment, overcome classical drug resistance, and achieve improved outcome in this presently incurable disease. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. G. Richardson, E. Weller, S. Jagannath, D. E. Avigan, M. Alsina, R. L. Schlossman, A. Mazumder, N. C. Munshi, I. M. Ghobrial, D. Doss, et al. Multicenter, Phase I, Dose-Escalation Trial of Lenalidomide Plus Bortezomib for Relapsed and Relapsed/Refractory Multiple Myeloma J. Clin. 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Jadersten, A.-M. Forsblom, H. Cattan, B. Christensson, E. K. Emanuelsson, M. Merup, L. Nilsson, J. Samuelsson, B. Sander, et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients PNAS, July 3, 2007; 104(27): 11406 - 11411. [Abstract] [Full Text] [PDF] S. Trudel, Z. H. Li, J. Rauw, R. E. Tiedemann, X. Y. Wen, and A. K. Stewart Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma Blood, June 15, 2007; 109(12): 5430 - 5438. [Abstract] [Full Text] [PDF] T. Kiziltepe, T. Hideshima, L. Catley, N. Raje, H. Yasui, N. Shiraishi, Y. Okawa, H. Ikeda, S. Vallet, S. Pozzi, et al. 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells Mol. Cancer Ther., June 1, 2007; 6(6): 1718 - 1727. [Abstract] [Full Text] [PDF] P. G. 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Fluorescence Imaging of Multiple Myeloma Cells in a Clinically Relevant SCID/NOD in Vivo Model: Biologic and Clinical Implications Cancer Res., October 15, 2003; 63(20): 6689 - 6696. [Abstract] [Full Text] [PDF] T. Hayashi, T. Hideshima, M. Akiyama, N. Raje, P. Richardson, D. Chauhan, and K. C. Anderson Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes Blood, August 15, 2003; 102(4): 1435 - 1442. [Abstract] [Full Text] [PDF] C.-K. Lee, B. Barlogie, N. Munshi, M. Zangari, A. Fassas, J. Jacobson, F. van Rhee, M. Cottler-Fox, F. Muwalla, and G. Tricot DTPACE: An Effective, Novel Combination Chemotherapy With Thalidomide for Previously Treated Patients With Myeloma J. Clin. Oncol., July 15, 2003; 21(14): 2732 - 2739. [Abstract] [Full Text] [PDF] P. H. Schafer, A. K. Gandhi, M. A. Loveland, R. S. Chen, H.-W. Man, P. P. M. Schnetkamp, G. Wolbring, S. Govinda, L. G. Corral, F. Payvandi, et al. 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