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Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo

Leukemia volume 17, pages 41–44 (2003)Cite this article

Abstract

We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beige-nude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct anti-tumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms.

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Acknowledgements

This work was supported by the Deutsche Krebshilfe, Bonn, Germany (SL), National Institutes of Health Grants RO-1 50947 and PO-1 78378, and the Doris Duke Distinguished Clinical Research Scientist Award (KCA).

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Authors and Affiliations

  1. Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, Boston, MA, USA

    S Lentzsch, R LeBlanc, K Podar, F Davies, B Lin, T Hideshima, L Catley & K C Anderson

  2. Celgene Corporation, Warren, NJ, USA

    D I Stirling

  3. University Medical Center, Charite, Humboldt University, Robert-Roessle-Klinik, Berlin, Germany

    S Lentzsch

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  1. S Lentzsch
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  2. R LeBlanc
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Lentzsch, S., LeBlanc, R., Podar, K. et al. Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia 17, 41–44 (2003). https://doi.org/10.1038/sj.leu.2402745

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  • DOI: https://doi.org/10.1038/sj.leu.2402745

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