Selective efficacy of depsipeptide in a xenograft model of Epstein-Barr virus-positive lymphoproliferative disorder
| Autor: | Bradley W. Blaser, Darshna Bhatt, Jim J. Xiao, Charles F. Eisenbeis, Srinivas Vourganti, Sameek Roychowdhury, Michael A. Caligiuri, Jason Chou, Mark R. Parthun, Robert A. Baiocchi, Ching-Shih Chen, Michael R. Grever, Chang Shi Chen, Amy K. Ferketich, Kenneth K. Chan, Aharon G. Freud |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Epstein-Barr Virus Infections Herpesvirus 4 Human medicine.drug_class Transplantation Heterologous Lymphoproliferative disorders Antineoplastic Agents Apoptosis Biology medicine.disease_cause Peptides Cyclic Romidepsin Viral Matrix Proteins Immunocompromised Host Mice hemic and lymphatic diseases Cell Line Tumor Depsipeptides medicine Animals Humans Enzyme Inhibitors Depsipeptide Histone deacetylase inhibitor NF-kappa B Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Flow Cytometry Epstein–Barr virus Burkitt Lymphoma Caspase Inhibitors Lymphoma Histone Deacetylase Inhibitors Disease Models Animal Oncology Proto-Oncogene Proteins c-bcl-2 Cancer research Burkitt's lymphoma Cell Division medicine.drug Thymidine |
| Zdroj: | Journal of the National Cancer Institute. 96(19) |
| ISSN: | 1460-2105 |
| Popis: | BACKGROUND Immune-compromised individuals are at increased risk for developing aggressive Epstein-Barr virus (EBV)-associated lymphoproliferative disorders after primary EBV infection or for reactivation of a preexisting latent EBV infection. We evaluated the effect of depsipeptide, a histone deacetylase inhibitor, on EBV-positive lymphoblastoid cell lines (LCLs) and Burkitt lymphoma cell lines in a mouse model and explored its mechanism of action in vitro. METHODS We studied EBV-transformed LCLs, which express a latent III (Lat-III) viral gene profile, as do some EBV-positive lymphoproliferative malignancies, and Burkitt lymphoma cell lines, which express a Lat-I viral gene profile. Cell lines were used to characterize depsipeptide-induced apoptosis, which was evaluated by flow cytometry. Flow cytometry, western blot analyses, and histone deacetylase inhibitors were used to investigate components of prodeath and survival pathways in vitro. We studied depsipeptide's effects on survival with a mouse xenograft model of EBV-positive human B-cell tumors (groups of 10 mice). All statistical tests were two-sided. RESULTS Depsipeptide (5 mg/m2 of body surface area) treatment was associated with statistically significantly improved survival of mice carrying Lat-III EBV-positive LCL tumors, compared with that of control-treated mice (day 30: for depsipeptide-treated mice, 90% survival, 95% confidence interval [CI] = 73.2% to 100%; for control-treated mice, 20% survival, 95% CI = 5.79% to 69.1%; P |
| Databáze: | OpenAIRE |
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