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Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors

The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields—TTFields) to...

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Autores principales: Branter, Joshua, Estevez-Cebrero, Maria, Diksin, Mohammed, Griffin, Michaela, Castellanos-Uribe, Marcos, May, Sean, Rahman, Ruman, Grundy, Richard, Basu, Surajit, Smith, Stuart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880247/
https://www.ncbi.nlm.nih.gov/pubmed/35216098
http://dx.doi.org/10.3390/ijms23041982
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author Branter, Joshua
Estevez-Cebrero, Maria
Diksin, Mohammed
Griffin, Michaela
Castellanos-Uribe, Marcos
May, Sean
Rahman, Ruman
Grundy, Richard
Basu, Surajit
Smith, Stuart
author_facet Branter, Joshua
Estevez-Cebrero, Maria
Diksin, Mohammed
Griffin, Michaela
Castellanos-Uribe, Marcos
May, Sean
Rahman, Ruman
Grundy, Richard
Basu, Surajit
Smith, Stuart
author_sort Branter, Joshua
collection PubMed
description The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields—TTFields) to the patient for the treatment of primary and recurrent Glioblastoma multiforme (GBM). Various mechanisms have been proposed to explain the effects of TTFields and other electrical therapies. Here, we present the first study of genome-wide expression of electrotherapy (delivered via TTFields or Deep Brain Stimulation (DBS)) on brain tumor cell lines. The effects of electric fields were assessed through gene expression arrays and combinational effects with chemotherapies. We observed that both DBS and TTFields significantly affected brain tumor cell line viability, with DBS promoting G0-phase accumulation and TTFields promoting G2-phase accumulation. Both treatments may be used to augment the efficacy of chemotherapy in vitro. Genome-wide expression assessment demonstrated significant overlap between the different electrical treatments, suggesting novel interactions with mitochondrial functioning and promoting endoplasmic reticulum stress. We demonstrate the in vitro efficacy of electric fields against adult and pediatric high-grade brain tumors and elucidate potential mechanisms of action for future study.
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spelling pubmed-88802472022-02-26 Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors Branter, Joshua Estevez-Cebrero, Maria Diksin, Mohammed Griffin, Michaela Castellanos-Uribe, Marcos May, Sean Rahman, Ruman Grundy, Richard Basu, Surajit Smith, Stuart Int J Mol Sci Article The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields—TTFields) to the patient for the treatment of primary and recurrent Glioblastoma multiforme (GBM). Various mechanisms have been proposed to explain the effects of TTFields and other electrical therapies. Here, we present the first study of genome-wide expression of electrotherapy (delivered via TTFields or Deep Brain Stimulation (DBS)) on brain tumor cell lines. The effects of electric fields were assessed through gene expression arrays and combinational effects with chemotherapies. We observed that both DBS and TTFields significantly affected brain tumor cell line viability, with DBS promoting G0-phase accumulation and TTFields promoting G2-phase accumulation. Both treatments may be used to augment the efficacy of chemotherapy in vitro. Genome-wide expression assessment demonstrated significant overlap between the different electrical treatments, suggesting novel interactions with mitochondrial functioning and promoting endoplasmic reticulum stress. We demonstrate the in vitro efficacy of electric fields against adult and pediatric high-grade brain tumors and elucidate potential mechanisms of action for future study. MDPI 2022-02-11 /pmc/articles/PMC8880247/ /pubmed/35216098 http://dx.doi.org/10.3390/ijms23041982 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Branter, Joshua
Estevez-Cebrero, Maria
Diksin, Mohammed
Griffin, Michaela
Castellanos-Uribe, Marcos
May, Sean
Rahman, Ruman
Grundy, Richard
Basu, Surajit
Smith, Stuart
Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors
title Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors
title_full Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors
title_fullStr Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors
title_full_unstemmed Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors
title_short Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors
title_sort genome-wide expression and anti-proliferative effects of electric field therapy on pediatric and adult brain tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880247/
https://www.ncbi.nlm.nih.gov/pubmed/35216098
http://dx.doi.org/10.3390/ijms23041982
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