1. p53 reactivation kills KSHV lymphomas efficiently in vitro and in vivo: new hope for treating aggressive viral lymphomas.
- Author
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Sarek G and Ojala PM
- Subjects
- Animals, Herpesvirus 8, Human growth & development, Humans, Lymphoma, AIDS-Related metabolism, Lymphoma, AIDS-Related pathology, Sarcoma, Kaposi metabolism, Sarcoma, Kaposi pathology, Signal Transduction physiology, Tumor Suppressor Protein p53 physiology, Herpesvirus 8, Human pathogenicity, Lymphoma, AIDS-Related therapy, Lymphoma, AIDS-Related virology, Sarcoma, Kaposi therapy, Sarcoma, Kaposi virology, Tumor Suppressor Protein p53 metabolism
- Abstract
KSHV infection is the causative agent in three different tumor types: Kaposi's sarcoma, a plasmablastic variant of multicentric Castelman's disease and an AIDS-related form of B cell lymphoproliferative disorder called primary effusion lymphoma (PEL). PEL manifests as an effusion malignancy in Kaposi's sarcoma patients with advanced AIDS, but also occurs in HIV-negative individuals. PEL is a very aggressive disease, and currently there are no efficient therapies for treating PEL. In our recent paper we report that p53 reactivation by a small molecule inhibitor of p53-MDM2 interaction, Nutlin-3a, induces selective and massive apoptosis in PEL cells, and has striking anti-tumor activity in a mouse xenograft PEL model. In the light of current treatment regimens for PEL, we discuss here the benefits of using reactivation of the p53 pathway as a novel principle for the treatment of this virally induced highly aggressive malignancy.
- Published
- 2007
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