Document Detail


Combination of hyperthermia and bortezomib results in additive killing in mantle cell lymphoma cells.
MedLine Citation:
PMID:  19670095     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The proteasome inhibitor bortezomib exhibits antitumor activity in many malignancies including mantle cell lymphoma (MCL). Unfortunately, many patients fail to respond to treatment or become refractory. Hyperthermia is an effective chemosensitizer that in combination with some chemotherapeutic agents has shown clinical activity in phase II and III studies. The aim of this study was to use MCL cell lines to investigate the potential benefit of combining clinically relevant doses of bortezomib with two different thermal doses (41.8 degrees C/120 min and 44 degrees C/30 min) that mimic the heterogeneity of the temperature distributions achieved within tumors during hyperthermia. Treated tumor cells were assessed for proliferation using the WST-1 assay and for apoptosis by annexin V staining, while heat shock protein (HSP) levels were determined following western blot analysis. Our results demonstrated that MCL cell lines that are sensitive to bortezomib are also thermosensitive and have low basal expression of hsp27, whereas the bortezomib-resistant MCL cell line strongly expresses hsp27 and is thermoresistant. Interestingly, pre-treatment of MCL cell lines with heat at the two different thermal doses, and the transient elevation of hsp27 and hsp70, do not impair their primary sensitivity to bortezomib. Finally, we show that the concurrent treatment of heat and bortezomib results in additive killing in MCL cell lines.In conclusion, these results suggest that the application of bortezomib, under thermal conditions, in mantle cell lymphoma cells may be beneficial and warrants further investigation.
Authors:
Valeria Milani; Monika Lorenz; Marc Weinkauf; Malte Rieken; Alessandro Pastore; Martin Dreyling; Rolf Issels
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group     Volume:  25     ISSN:  1464-5157     ISO Abbreviation:  Int J Hyperthermia     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-08-11     Completed Date:  2009-10-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8508395     Medline TA:  Int J Hyperthermia     Country:  England    
Other Details:
Languages:  eng     Pagination:  262-72     Citation Subset:  IM    
Affiliation:
Department of Medical Oncology, University Medical Center Grosshadern, 81377 Munich, Germany. valeria.milani@med.uni-muenchen.de
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Boronic Acids / therapeutic use*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Combined Modality Therapy
Humans
Hyperthermia, Induced*
Lymphoma, Mantle-Cell / drug therapy,  therapy*
Pyrazines / therapeutic use*
Chemical
Reg. No./Substance:
0/Boronic Acids; 0/Pyrazines; 0/bortezomib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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