Document Detail


Lenalidomide synergizes with dexamethasone to induce growth arrest and apoptosis of mantle cell lymphoma cells in vitro and in vivo.
MedLine Citation:
PMID:  21047686     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Mantle cell lymphoma (MCL) frequently relapses after therapy and new therapeutic regimens are needed. Lenalidomide (LEN), a thalidomide analogue, displays direct cytotoxicity against MCL cells. This study was undertaken to evaluate the combined therapeutic effect of LEN and dexamethasone (DEX) on MCL. LEN synergized with DEX to induce the growth inhibition and apoptosis of both established MCL cells and freshly isolated MCL cells from refractory or relapsed MCL patients. The synergy was more significant in freshly isolated patients' MCL cells than established MCL cells. Cell cycle analysis showed that LEN enhanced DEX-induced G(0)/G(1) arrest. The effect of the LEN and DEX combination on apoptotic induction was mainly through mitochondrial signaling pathways, as demonstrated by phosphorylation of bcl-2 and up-regulation of proapoptotic proteins Bax, Bad and Bim, and the subsequent activation of caspase-9, caspase-3, and cleavage of PARP. Importantly, the combination of LEN and DEX delayed the tumor growth and improved the survival of MCL-bearing mice. The results support the use of the LEN and DEX combination as a new therapeutic regimen in clinical trials of MCL.
Authors:
Zhengzi Qian; Liang Zhang; Zhen Cai; Luhong Sun; Huaqing Wang; Qing Yi; Michael Wang
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Publication Detail:
Type:  Journal Article     Date:  2010-11-02
Journal Detail:
Title:  Leukemia research     Volume:  35     ISSN:  1873-5835     ISO Abbreviation:  Leuk. Res.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  380-6     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
Affiliation:
Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA; Department of Lymphoma, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
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