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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-06-1874. This Article Full Text (PDF) All Versions of this Article: 2002-06-1874v1 101/2/703    most recent Alert me when this article is cited Alert me if a correction is posted 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 Social Bookmarking                   What's this? Submitted June 25, 2002 Accepted August 8, 2002 Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu Teru Hideshima, Masaharu Akiyama, Toshiaki Hayashi, Paul Richardson, Robert Schlossman, Dharminder Chauhan, and Kenneth C Anderson* Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA * Corresponding author; email: kenneth_anderson{at}dfci.harvard.edu. p38 mitogen-activated protein kinase (MAPK) is a member of the MAPK family which is activated by cytokines and growth factors, but its role in pathogenesis of multiple myeloma (MM) is unknown. In this study, we demonstrate that the specific p38 MAPK inhibitor VX-745 inhibits IL-6 and VEGF secretion in bone marrow stromal cells (BMSCs), without affecting their viability. TNF--induced IL-6 secretion in BMSCs is also inhibited by VX-745. Importantly, VX-745 inhibits both MM cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that it can inhibit paracrine MM cell growth in the BM milieu and overcome cell adhesion related drug resistance. These studies therefore identify p38 MAPK as a novel therapeutic target to overcome drug resistance and improve patient outcome in MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. K. Azab, J. M. Runnels, C. Pitsillides, A.-S. Moreau, F. Azab, X. Leleu, X. Jia, R. Wright, B. Ospina, A. L. Carlson, et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy Blood, April 30, 2009; 113(18): 4341 - 4351. [Abstract] [Full Text] [PDF] A. Purushothaman, L. Chen, Y. Yang, and R. D. 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