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Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the...

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Autores principales: Bosnjak, Masa, Jesenko, Tanja, Kamensek, Urska, Sersa, Gregor, Lavrencak, Jaka, Heller, Loree, Cemazar, Maja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836069/
https://www.ncbi.nlm.nih.gov/pubmed/29382170
http://dx.doi.org/10.3390/cancers10020037
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author Bosnjak, Masa
Jesenko, Tanja
Kamensek, Urska
Sersa, Gregor
Lavrencak, Jaka
Heller, Loree
Cemazar, Maja
author_facet Bosnjak, Masa
Jesenko, Tanja
Kamensek, Urska
Sersa, Gregor
Lavrencak, Jaka
Heller, Loree
Cemazar, Maja
author_sort Bosnjak, Masa
collection PubMed
description Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were determined. GET of all three plasmids caused significant growth delay in melanoma tumors; nevertheless, the effect of pVAX1 was significantly greater than pControl. While DNA sensors in vivo were not upregulated significantly, cytokines IFN β and TNF α were upregulated after GET of pVAX1. In vitro, the mRNAs of some cytosolic DNA sensors were overexpressed after GET; however, with no significant difference among the three plasmids. In summary, although differences in antitumor effects were observed among control plasmids in vivo, no differences in cellular responses to plasmid GET were detected in tumor cells in vitro. Thus, the tumor microenvironment as well as some plasmid properties are most probably responsible for the antitumor effectiveness.
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spelling pubmed-58360692018-03-07 Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma Bosnjak, Masa Jesenko, Tanja Kamensek, Urska Sersa, Gregor Lavrencak, Jaka Heller, Loree Cemazar, Maja Cancers (Basel) Article Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were determined. GET of all three plasmids caused significant growth delay in melanoma tumors; nevertheless, the effect of pVAX1 was significantly greater than pControl. While DNA sensors in vivo were not upregulated significantly, cytokines IFN β and TNF α were upregulated after GET of pVAX1. In vitro, the mRNAs of some cytosolic DNA sensors were overexpressed after GET; however, with no significant difference among the three plasmids. In summary, although differences in antitumor effects were observed among control plasmids in vivo, no differences in cellular responses to plasmid GET were detected in tumor cells in vitro. Thus, the tumor microenvironment as well as some plasmid properties are most probably responsible for the antitumor effectiveness. MDPI 2018-01-29 /pmc/articles/PMC5836069/ /pubmed/29382170 http://dx.doi.org/10.3390/cancers10020037 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bosnjak, Masa
Jesenko, Tanja
Kamensek, Urska
Sersa, Gregor
Lavrencak, Jaka
Heller, Loree
Cemazar, Maja
Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma
title Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma
title_full Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma
title_fullStr Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma
title_full_unstemmed Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma
title_short Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma
title_sort electrotransfer of different control plasmids elicits different antitumor effectiveness in b16.f10 melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836069/
https://www.ncbi.nlm.nih.gov/pubmed/29382170
http://dx.doi.org/10.3390/cancers10020037
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