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Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation

In this work, we have investigated the feasibility of sub-microsecond range irreversible electroporation (IRE) with and without calcium electroporation in vivo. As a model, BALB/C mice were used and bioluminescent SP2/0 myeloma tumor models were developed. Tumors were treated with two separate pulse...

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Autores principales: Novickij, Vitalij, Čėsna, Robertas, Perminaitė, Emilija, Zinkevičienė, Auksė, Characiejus, Dainius, Novickij, Jurij, Šatkauskas, Saulius, Ruzgys, Paulius, Girkontaitė, Irutė
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896087/
https://www.ncbi.nlm.nih.gov/pubmed/31717542
http://dx.doi.org/10.3390/cancers11111763
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author Novickij, Vitalij
Čėsna, Robertas
Perminaitė, Emilija
Zinkevičienė, Auksė
Characiejus, Dainius
Novickij, Jurij
Šatkauskas, Saulius
Ruzgys, Paulius
Girkontaitė, Irutė
author_facet Novickij, Vitalij
Čėsna, Robertas
Perminaitė, Emilija
Zinkevičienė, Auksė
Characiejus, Dainius
Novickij, Jurij
Šatkauskas, Saulius
Ruzgys, Paulius
Girkontaitė, Irutė
author_sort Novickij, Vitalij
collection PubMed
description In this work, we have investigated the feasibility of sub-microsecond range irreversible electroporation (IRE) with and without calcium electroporation in vivo. As a model, BALB/C mice were used and bioluminescent SP2/0 myeloma tumor models were developed. Tumors were treated with two separate pulsed electric field (PEF) pulsing protocols PEF1: 12 kV/cm × 200 ns × 500 (0.006 J/pulse) and PEF2: 12 kV/cm × 500 ns × 500 (0.015 J/pulse), which were delivered with and without Ca(2+) (168 mM) using parallel plate electrodes at a repetition frequency of 100 Hz. Both PEF1 and PEF2 treatments reduced tumor growth and prolonged the life span of the mice, however, the PEF2 protocol was more efficient. The delay in tumor renewal was the biggest when a combination of IRE with calcium electroporation was used, however, we did not obtain significant differences in the final mouse survival compared to PEF2 alone. Anti-tumor immune responses were also investigated after treatment with PEF2 and PEF2+Ca. In both cases the treated mice had enlarged spleens and increased spleen T cell numbers, lower percentages of suppressor cell subsets (conventional CD4(+)CD25(+) Treg, CD4(+)CD25(−)DX5(+) Tr1, CD8(+)DX5(+), CD4(+)CD28(−), CD8(+)CD28(−)), changed proportions of Tcm and Tef/Tem T cells in the spleen and increased amount of tumor cell specific antibodies in the sera. The treatment based on IRE was effective against primary tumors, destroyed the tumor microenvironment and induced an anti-tumor immune response, however, it was not sufficient for complete control of tumor metastasis.
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spelling pubmed-68960872019-12-23 Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation Novickij, Vitalij Čėsna, Robertas Perminaitė, Emilija Zinkevičienė, Auksė Characiejus, Dainius Novickij, Jurij Šatkauskas, Saulius Ruzgys, Paulius Girkontaitė, Irutė Cancers (Basel) Article In this work, we have investigated the feasibility of sub-microsecond range irreversible electroporation (IRE) with and without calcium electroporation in vivo. As a model, BALB/C mice were used and bioluminescent SP2/0 myeloma tumor models were developed. Tumors were treated with two separate pulsed electric field (PEF) pulsing protocols PEF1: 12 kV/cm × 200 ns × 500 (0.006 J/pulse) and PEF2: 12 kV/cm × 500 ns × 500 (0.015 J/pulse), which were delivered with and without Ca(2+) (168 mM) using parallel plate electrodes at a repetition frequency of 100 Hz. Both PEF1 and PEF2 treatments reduced tumor growth and prolonged the life span of the mice, however, the PEF2 protocol was more efficient. The delay in tumor renewal was the biggest when a combination of IRE with calcium electroporation was used, however, we did not obtain significant differences in the final mouse survival compared to PEF2 alone. Anti-tumor immune responses were also investigated after treatment with PEF2 and PEF2+Ca. In both cases the treated mice had enlarged spleens and increased spleen T cell numbers, lower percentages of suppressor cell subsets (conventional CD4(+)CD25(+) Treg, CD4(+)CD25(−)DX5(+) Tr1, CD8(+)DX5(+), CD4(+)CD28(−), CD8(+)CD28(−)), changed proportions of Tcm and Tef/Tem T cells in the spleen and increased amount of tumor cell specific antibodies in the sera. The treatment based on IRE was effective against primary tumors, destroyed the tumor microenvironment and induced an anti-tumor immune response, however, it was not sufficient for complete control of tumor metastasis. MDPI 2019-11-09 /pmc/articles/PMC6896087/ /pubmed/31717542 http://dx.doi.org/10.3390/cancers11111763 Text en © 2019 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
Novickij, Vitalij
Čėsna, Robertas
Perminaitė, Emilija
Zinkevičienė, Auksė
Characiejus, Dainius
Novickij, Jurij
Šatkauskas, Saulius
Ruzgys, Paulius
Girkontaitė, Irutė
Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation
title Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation
title_full Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation
title_fullStr Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation
title_full_unstemmed Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation
title_short Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation
title_sort antitumor response and immunomodulatory effects of sub-microsecond irreversible electroporation and its combination with calcium electroporation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896087/
https://www.ncbi.nlm.nih.gov/pubmed/31717542
http://dx.doi.org/10.3390/cancers11111763
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