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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-08-2525. This Article Full Text (PDF) All Versions of this Article: 2002-08-2525v1 101/6/2321    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 Ghosh, S. K Articles by Harrington, W. J Search for Related Content PubMed PubMed Citation Articles by Ghosh, S. K Articles by Harrington, W. J Social Bookmarking                   What's this? Submitted August 16, 2002 Accepted October 15, 2002 Potentiation of TRAIL-induced apoptosis in primary effusion lymphoma through azidothymidine-mediated inhibition of NF-B Subrata K Ghosh, Charles Wood, Lawrence H Boise, Abdul M Mian, Vadim V Deyev, Gerold Feuer, Ngoc L Toomey, Nicole C Shank, Lisa Cabral, Glen N Barber, and William J Harrington* Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center/Universityof Miami School of Medicine, Miami, FL, USA Department of Microbiology and Immunology, University of Nebraska at Lincoln, Lincoln, NE, USA Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center/Universityof Miami School of Medicine, Miami, FL, USA Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY, USA * Corresponding author; email: wharring{at}med.miami.edu. The survival of viral mediated lymphomas depends upon constitutive nuclear factor kappa B activity (NF-B). AIDS related Human Herpes Virus Type 8 (HHV-8) associated Primary Effusion Lymphoma (PEL) responds poorly to chemotherapy and is almost invariably fatal. We have previously demonstrated that the antiviral combination, interferon alpha (IFN-) and Azidothymidine (AZT), induces apoptosis in PEL cell lines. We therefore employed these agents as therapy for an AIDS patient with PEL. The patient had a dramatic response with complete resolution of his malignant effusion in 5 days. In PEL cells, the death receptor ligand TRAIL is markedly upregulated by IFN- however, signals transduced by death receptors may also activate an anti-apoptotic response mediated by NF-B. In both the primary tumor cells from our patient and PEL cell lines, AZT selectively blocked nuclear entry of the NF-B heterodimer p50 and p65, an effect not seen with other non-thymidine antiviral nucleosides. AZT monophosphate (AZTMP), the principal intracellular metabolite, inhibited phosphorylation and degradation of IB by the IB kinase complex (IKK). AZT and IFN- mediated apoptosis was blocked by expression and nuclear localization of an IB-resistant form of NF-B (the p50 subunit linked to the trans-activation domain of HSV VP16). The pro-apoptotic effect of AZT and IFN- in PEL occurs through the concomitant activation of TRAIL and blockade of NF-B and represents a novel anti-viral based therapy for a virally mediated tumor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. L. Calabro, P. Gasperini, I. M. Di Gangi, S. Indraccolo, M. Barbierato, A. Amadori, and L. Chieco-Bianchi Antineoplastic activity of lentiviral vectors expressing interferon-{alpha} in a preclinical model of primary effusion lymphoma Blood, May 7, 2009; 113(19): 4525 - 4533. [Abstract] [Full Text] [PDF] A. Carbone, E. Cesarman, M. Spina, A. Gloghini, and T. F. Schulz HIV-associated lymphomas and gamma-herpesviruses Blood, February 5, 2009; 113(6): 1213 - 1224. [Abstract] [Full Text] [PDF] D. A. Davis, K. E. Singer, I. P. Reynolds, M. Haque, and R. Yarchoan Hypoxia Enhances the Phosphorylation and Cytotoxicity of Ganciclovir and Zidovudine in Kaposi's Sarcoma-Associated Herpesvirus Infected Cells Cancer Res., July 15, 2007; 67(14): 7003 - 7010. [Abstract] [Full Text] [PDF] C. E. Petre, S.-H. Sin, and D. P. Dittmer Functional p53 Signaling in Kaposi's Sarcoma-Associated Herpesvirus Lymphomas: Implications for Therapy J. Virol., February 15, 2007; 81(4): 1912 - 1922. [Abstract] [Full Text] [PDF] A. Datta, M. Bellon, U. Sinha-Datta, A. Bazarbachi, Y. Lepelletier, D. Canioni, T. A. Waldmann, O. Hermine, and C. Nicot Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence Blood, August 1, 2006; 108(3): 1021 - 1029. [Abstract] [Full Text] [PDF] M. Kurokawa, S. K. Ghosh, J. C. Ramos, A. M. Mian, N. L. Toomey, L. Cabral, D. Whitby, G. N. Barber, D. P. Dittmer, and W. J. Harrington Jr Azidothymidine inhibits NF-{kappa}B and induces Epstein-Barr virus gene expression in Burkitt lymphoma Blood, July 1, 2005; 106(1): 235 - 240. [Abstract] [Full Text] [PDF]

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