Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma
ID:
状态:
发布时间July 20, 2010
, 更新时间 March 27, 2012
物种:
Mus musculus
摘要:
Primary effusion lymphoma is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposi’s sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients yet efforts to develop superior therapeutic approaches have been impeded by lack of animal models that more accurately mimic human disease. To address this issue we developed a direct xenograft model, UM-PEL-1, by transferring freshly-isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth. We utilized this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. Transcriptome analysis by genomic arrays revealed that bortezomib downregulated cell cycle progression, DNA replication, and Myc-target genes. The microarray analysis was conducted on mice bearing UM-PEL-1 xenografts after treatment for 24 hours with PBS or bortezomib. Both arms of the experiment had three mice and the RNA was pooled from the three treated mice for gene expression analysis.