Document Detail


Verapamil enhances the antitumoral efficacy of oncolytic adenoviruses.
MedLine Citation:
PMID:  20179683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The therapeutic potential of oncolytic adenoviruses is limited by the rate of adenovirus release. Based on the observation that several viruses induce cell death and progeny release by disrupting intracellular calcium homeostasis, we hypothesized that the alteration in intracellular calcium concentration induced by verapamil could improve the rate of virus release and spread, eventually enhancing the antitumoral activity of oncolytic adenoviruses. Our results indicate that verapamil substantially enhanced the release of adenovirus from a variety of cell types resulting in an improved cell-to-cell spread and cytotoxicity. Furthermore, the combination of the systemic administration of an oncolytic adenovirus (ICOVIR-5) with verapamil in vivo greatly improved its antitumoral activity in two different tumor xenograft models without affecting the selectivity of this virus. Overall, our findings indicate that verapamil provides a new, safe, and versatile way to improve the antitumoral potency of oncolytic adenoviruses in the clinical setting.
Authors:
Alena Gros; Cristina Puig; Sonia Guedan; Juan José Rojas; Ramon Alemany; Manel Cascallo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-23
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  18     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-03     Completed Date:  2010-07-30     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  903-11     Citation Subset:  IM    
Affiliation:
Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / drug effects,  genetics,  physiology*
Animals
Blotting, Western
Cell Line
Cell Line, Tumor
Genetic Vectors
Humans
Male
Mice
Mice, Inbred BALB C
Neoplasms / therapy
Oncolytic Virotherapy / methods*
Oncolytic Viruses / drug effects,  genetics,  physiology*
Verapamil / therapeutic use*
Virus Release / drug effects
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
52-53-9/Verapamil
Comments/Corrections

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


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