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Double E1B 19 kDa- and E1B 55 kDa-deleted oncolytic adenovirus in combination with radiotherapy elicits an enhanced anti-tumor effect

Authors
 J Kim  ;  P-H Kim  ;  JY Yoo  ;  A-R Yoon  ;  HJ Choi  ;  J Seong  ;  I-W Kim  ;  J-H Kim  ;  C-O Yun 
Citation
 GENE THERAPY, Vol.16(9) : 1111-1121, 2009 
Journal Title
 GENE THERAPY 
ISSN
 0969-7128 
Issue Date
2009
MeSH
Adenoviridae/genetics* ; Adenovirus E1B Proteins/genetics* ; Animals ; Apoptosis/genetics ; Combined Modality Therapy ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oncolytic Virotherapy/methods* ; Oncolytic Viruses/genetics* ; Uterine Cervical Neoplasms/pathology ; Uterine Cervical Neoplasms/radiotherapy ; Uterine Cervical Neoplasms/therapy* ; Xenograft Model Antitumor Assays
Keywords
oncolytic adenovirus ; radiation ; E1B 19 kDa ; apoptosis
Abstract
Radiation therapy, a mainstay for anti-tumor therapeutic regimens for a variety of tumor types, triggers tumor cell apoptotic pathways by either directly eliciting DNA damage or indirectly inducing the formation of oxygen radicals. In an effort to augment radiation therapy, we generated a double E1B 19 kDa- and E1B 55 kDa-deleted oncolytic adenovirus (Ad-DeltaE1B19/55). In combination with radiotherapy, greater cytotoxicity was observed for Ad-DeltaE1B19/55 than for the single E1B 55 kDa-deleted oncolytic Ad (Ad-DeltaE1B55). Consistent with this observation, higher levels of p53, phospho-p53, phospho-Chk1, phospho-Chk2, PI3K (phosphatidylinositol-3-kinase), phospho-AKT, cytochrome c, and cleavage of PARP (poly (ADP-ribose) polymerase) and caspase-3 were observed in cells treated with Ad-DeltaE1B19/55 compared with those treated with Ad-DeltaE1B55, indicating that the E1B 19 kDa present in Ad-DeltaE1B55 may partially block radiation-induced apoptosis. A significant therapeutic benefit was also observed in vivo when oncolytic Ads and radiation were combined. Tumors treated with Ad-DeltaE1B19/55 and radiation showed large areas of necrosis and apoptosis with the corresponding induction of p53. Finally, consistent with in vitro observations, the combination of Ad-DeltaE1B19/55 and radiation was more efficacious than the combination of Ad-DeltaE1B55 and radiation. Taken together, these results present a strong therapeutic rationale for combining radiation therapy with E1B 19 kDa-deleted oncolytic Ad.
Full Text
http://www.nature.com/gt/journal/v16/n9/full/gt200972a.html
DOI
10.1038/gt.2009.72
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Kim, Pyung Hwan(김평환)
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Yun, Chae Ok(윤채옥)
Choi, Hye Jin(최혜진) ORCID logo https://orcid.org/0000-0001-5917-1400
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104645
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