Abstract | BACKGROUND: Clinical trials have indicated that preclinical results obtained with human tumor xenografts in mouse models may overstate the potential of adenovirus (Ad)-mediated oncolytic therapies. We have previously demonstrated that the replication of human Ads depends on cyclin E dysregulation or overexpression in cancer cells. ED-1 cell derived from mouse lung adenocarcinomas triggered by transgenic overexpression of human cyclin E may be applied to investigate the antitumor efficacy of oncolytic Ads. METHODS: RESULTS: Murine ED-1 cells were permissive for human Ad replication and Ad-cycE repressed ED-1 tumor growth in immunocompetent FVB mice. ED-1 cells destroyed by oncolytic Ads in tumors were encircled in capsule-like structures, while cells outside the capsules were not infected and survived the treatment. CONCLUSION: Ad-cycE can target cyclin E overexpression in cancer cells and repress tumor growth in syngeneic mouse models. The capsule structures formed after Ad intratumoral injection may prevent viral particles from spreading to the entire tumor.
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Authors | Pei-Hsin Cheng, Xiao-Mei Rao, Stephen L Wechman, Xiao-Feng Li, Kelly M McMasters, Heshan Sam Zhou |
Journal | BMC cancer
(BMC Cancer)
Vol. 15
Pg. 716
(Oct 16 2015)
ISSN: 1471-2407 [Electronic] England |
PMID | 26475304
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adenocarcinoma
(genetics, therapy)
- Adenoviridae
(genetics)
- Animals
- Cell Line, Tumor
- Cell Proliferation
(genetics)
- Cyclin E
(biosynthesis, genetics)
- Disease Models, Animal
- Gene Expression Regulation, Neoplastic
- Humans
- Isografts
- Lung Neoplasms
(genetics, therapy)
- Mice
- Oncolytic Virotherapy
- Oncolytic Viruses
- Xenograft Model Antitumor Assays
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