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E1B-55 kDa-Defective Adenoviruses Activate p53 in Mesothelioma and Enhance Cytotoxicity of Anticancer Agents.
MedLine Citation:
PMID:  23154556     Owner:  NLM     Status:  Publisher    
INTRODUCTION:: Genetic characterization of malignant mesothelioma shows a homozygous deletion of the INK4A/ARF locus, which results in inactivation of the p53 pathways. METHODS:: We examined possible antitumor effects of adenoviruses with a deletion of the E1B-55kD gene (Ad-delE1B55) on mesothelioma and investigated combinatory actions with the first-line chemotherapeutic agents. RESULTS:: Ad-delE1B55 produced cytotoxicity on mesothelioma cells, which was associated with p53 phosphorylation, pRb dephosphorylation, and cleavage of caspases. Ad-delE1B55-infected cells displayed hyperploidy at the cell-cycle analysis and showed enlarged nuclear configurations. Combination of Ad-delE1B55 plus cisplatin or pemetrexed produced antitumor effects in vitro. Furthermore, Ad-delE1B55 and cisplatin showed combinatory effects in an orthotopic animal model. CONCLUSIONS:: Cell death caused by Ad-delE1B55 is attributable to cell-cycle arrest at M-phase checkpoint followed by activated apoptotic pathways, and combination of the first-line chemotherapeutic agents and the oncolytic adenovirus is a potential therapeutic for mesothelioma.
Makako Yamanaka; Yuji Tada; Kiyoko Kawamura; Quanhai Li; Shinya Okamoto; Kuan Chai; Sana Yokoi; Min Liang; Toshihiko Fukamachi; Hiroshi Kobayashi; Naoto Yamaguchi; Atsushi Kitamura; Hideaki Shimada; Kenzo Hiroshima; Yuichi Takiguchi; Koichiro Tatsumi; Masatoshi Tagawa
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Publication Detail:
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  7     ISSN:  1556-1380     ISO Abbreviation:  J Thorac Oncol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1850-1857     Citation Subset:  -    
Divisions of *Pathology and Cell Therapy and †Translational Genomics, Chiba Cancer Center Research Institute, Chiba, Japan; Departments of ‡Respirology, §Molecular Biology and Oncology, and ‖Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan; Departments of ¶Biochemistry and #Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan; **TOT Shanghai RD Center, Shanghai, China; ††Department of Surgery, School of Medicine, Toho University, Tokyo, Japan; and ‡‡Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
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