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Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice

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...

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Autores principales: Cheng, Pei-Hsin, Rao, Xiao-Mei, Wechman, Stephen L., Li, Xiao-Feng, McMasters, Kelly M., Zhou, Heshan Sam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609153/
https://www.ncbi.nlm.nih.gov/pubmed/26475304
http://dx.doi.org/10.1186/s12885-015-1731-x
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author Cheng, Pei-Hsin
Rao, Xiao-Mei
Wechman, Stephen L.
Li, Xiao-Feng
McMasters, Kelly M.
Zhou, Heshan Sam
author_facet Cheng, Pei-Hsin
Rao, Xiao-Mei
Wechman, Stephen L.
Li, Xiao-Feng
McMasters, Kelly M.
Zhou, Heshan Sam
author_sort Cheng, Pei-Hsin
collection PubMed
description 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: Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies. 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1731-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-46091532015-10-18 Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice Cheng, Pei-Hsin Rao, Xiao-Mei Wechman, Stephen L. Li, Xiao-Feng McMasters, Kelly M. Zhou, Heshan Sam BMC Cancer Research Article 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: Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies. 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1731-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-16 /pmc/articles/PMC4609153/ /pubmed/26475304 http://dx.doi.org/10.1186/s12885-015-1731-x Text en © Cheng et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Cheng, Pei-Hsin
Rao, Xiao-Mei
Wechman, Stephen L.
Li, Xiao-Feng
McMasters, Kelly M.
Zhou, Heshan Sam
Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice
title Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice
title_full Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice
title_fullStr Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice
title_full_unstemmed Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice
title_short Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice
title_sort oncolytic adenovirus targeting cyclin e overexpression repressed tumor growth in syngeneic immunocompetent mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609153/
https://www.ncbi.nlm.nih.gov/pubmed/26475304
http://dx.doi.org/10.1186/s12885-015-1731-x
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