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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6896087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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