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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4063-4070. Prepublished online as a Blood First Edition Paper on January 19, 2006; DOI 10.1182/blood-2005-09-3870. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3870v1 107/10/4063    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 Goel, A. Articles by Russell, S. J. Search for Related Content PubMed PubMed Citation Articles by Goel, A. Articles by Russell, S. J. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Synergistic activity of the proteasome inhibitor PS-341 with non-myeloablative 153-Sm-EDTMP skeletally targeted radiotherapy in an orthotopic model of multiple myeloma Apollina Goel, Angela Dispenzieri, Susan M. Geyer, Suzanne Greiner, Kah-Whye Peng, and Stephen J. Russell From the Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN; the Division of Hematology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN; and the Biostatistics, Mayo Clinic College of Medicine, Rochester, MN. Multiple myeloma is a highly radiosensitive skeletal malignancy, but bone-seeking radionuclides have not yet found their place in disease management. We previously reported that the proteasome inhibitor PS-341 selectively sensitizes myeloma cells to the lethal effects of ionizing radiation. To extend these observations to an in vivo model, we combined PS-341 with the bone-seeking radionuclide 153-Sm-EDTMP. In vitro clonogenic assays demonstrated synergistic killing of myeloma cells exposed to both PS-341 and 153-Sm-EDTMP. Using the orthotopic, syngeneic 5TGM1 myeloma model, the median survivals of mice treated with saline, 2 doses of PS-341 (0.5 mg/kg), or a single nonmyeloablative dose of 153-Sm-EDTMP (22.5 MBq) were 21, 22, and 28 days, respectively. In contrast, mice treated with combination therapy comprising 2 doses of PS-341 (0.5 mg/kg), 1 day prior to and 1 day following 153-Sm-EDTMP (22.5 MBq) showed a significantly prolonged median survival of 49 days (P < .001). In addition to prolonged survival, this treatment combination yielded reduced clonogenicity of bone marrow–resident 5TGM1 cells, reduced serum myeloma–associated paraprotein levels, and better preservation of bone mineral density. Myelosuppression, determined by peripheral blood cell counts and clonogenicity assays of hematopoietic progenitors, did not differ between animals treated with 153-Sm-EDTMP alone versus those treated with the combination of PS-341 plus 153-Sm-EDTMP. PS-341 is a potent, selective in vivo radiosensitizer that may substantially affect the efficacy of skeletal-targeted radiotherapy in multiple myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Jagani, K. Song, J. L. Kutok, M. R. Dewar, A. Melet, T. Santos, A. Grassian, S. Ghaffari, C. Wu, R. Ren, et al. Proteasome Inhibition Causes Regression of Leukemia and Abrogates BCR-ABL-Induced Evasion of Apoptosis in Part through Regulation of Forkhead Tumor Suppressors Cancer Res., August 15, 2009; 69(16): 6546 - 6555. [Abstract] [Full Text] [PDF] J. R. Berenson, O. Yellin, R. Patel, H. Duvivier, Y. Nassir, R. Mapes, C. D. Abaya, and R. A. Swift A Phase I Study of Samarium Lexidronam/Bortezomib Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma Clin. Cancer Res., February 1, 2009; 15(3): 1069 - 1075. [Abstract] [Full Text] [PDF] K. Kim, J. M. Brush, P. A. Watson, N. A. Cacalano, K. S. Iwamoto, and W. H. McBride Epidermal Growth Factor Receptor vIII Expression in U87 Glioblastoma Cells Alters Their Proteasome Composition, Function, and Response to Irradiation Mol. Cancer Res., March 1, 2008; 6(3): 426 - 434. [Abstract] [Full Text] [PDF] A. Goel, S. K. Carlson, K. L. Classic, S. Greiner, S. Naik, A. T. Power, J. C. Bell, and S. J. Russell Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV({Delta}51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene Blood, October 1, 2007; 110(7): 2342 - 2350. [Abstract] [Full Text] [PDF]

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