Understanding the role of calcium-mediated cell death in high-frequency irreversible electroporation. Wasson, E. M., Alinezhadbalalami, N., Brock, R. M., Allen, I. C., Verbridge, S. S., & Davalos, R. V. Bioelectrochemistry, 131:107369, 2020. 1878-562x Wasson, Elisa M Alinezhadbalalami, Nastaran Brock, Rebecca M Allen, Irving C Verbridge, Scott S Davalos, Rafael V P01 CA207206/CA/NCI NIH HHS/United States P30 CA012197/CA/NCI NIH HHS/United States R01 CA213423/CA/NCI NIH HHS/United States Journal Article Netherlands 2019/11/11 Bioelectrochemistry. 2020 Feb;131:107369. doi: 10.1016/j.bioelechem.2019.107369. Epub 2019 Sep 6.
doi  abstract   bibtex   
High-frequency irreversible electroporation (H-FIRE) is an emerging electroporation-based therapy used to ablate cancerous tissue. Treatment consists of delivering short, bipolar pulses (1-10μs) in a series of 80-100 bursts (1 burst/s, 100μs on-time). Reducing pulse duration leads to reduced treatment volumes compared to traditional IRE, therefore larger voltages must be applied to generate ablations comparable in size. We show that adjuvant calcium enhances ablation area in vitro for H-FIRE treatments of several pulse durations (1, 2, 5, 10μs). Furthermore, H-FIRE treatment using 10μs pulses delivered with 1mM CaCl(2) results in cell death thresholds (771±129V/cm) comparable to IRE thresholds without calcium (698±103V/cm). Quantifying the reversible electroporation threshold revealed that CaCl(2) enhances the permeabilization of cells compared to a NaCl control. Gene expression analysis determined that CaCl(2) upregulates expression of eIFB5 and 60S ribosomal subunit genes while downregulating NOX1/4, leading to increased signaling in pathways that may cause necroptosis. The opposite was found for control treatment without CaCl(2) suggesting cells experience an increase in pro survival signaling. Our study is the first to identify key genes and signaling pathways responsible for differences in cell response to H-FIRE treatment with and without calcium.
@article{RN142,
   author = {Wasson, E. M. and Alinezhadbalalami, N. and Brock, R. M. and Allen, I. C. and Verbridge, S. S. and Davalos, R. V.},
   title = {Understanding the role of calcium-mediated cell death in high-frequency irreversible electroporation},
   journal = {Bioelectrochemistry},
   volume = {131},
   pages = {107369},
   note = {1878-562x
Wasson, Elisa M
Alinezhadbalalami, Nastaran
Brock, Rebecca M
Allen, Irving C
Verbridge, Scott S
Davalos, Rafael V
P01 CA207206/CA/NCI NIH HHS/United States
P30 CA012197/CA/NCI NIH HHS/United States
R01 CA213423/CA/NCI NIH HHS/United States
Journal Article
Netherlands
2019/11/11
Bioelectrochemistry. 2020 Feb;131:107369. doi: 10.1016/j.bioelechem.2019.107369. Epub 2019 Sep 6.},
   abstract = {High-frequency irreversible electroporation (H-FIRE) is an emerging electroporation-based therapy used to ablate cancerous tissue. Treatment consists of delivering short, bipolar pulses (1-10μs) in a series of 80-100 bursts (1 burst/s, 100μs on-time). Reducing pulse duration leads to reduced treatment volumes compared to traditional IRE, therefore larger voltages must be applied to generate ablations comparable in size. We show that adjuvant calcium enhances ablation area in vitro for H-FIRE treatments of several pulse durations (1, 2, 5, 10μs). Furthermore, H-FIRE treatment using 10μs pulses delivered with 1mM CaCl(2) results in cell death thresholds (771±129V/cm) comparable to IRE thresholds without calcium (698±103V/cm). Quantifying the reversible electroporation threshold revealed that CaCl(2) enhances the permeabilization of cells compared to a NaCl control. Gene expression analysis determined that CaCl(2) upregulates expression of eIFB5 and 60S ribosomal subunit genes while downregulating NOX1/4, leading to increased signaling in pathways that may cause necroptosis. The opposite was found for control treatment without CaCl(2) suggesting cells experience an increase in pro survival signaling. Our study is the first to identify key genes and signaling pathways responsible for differences in cell response to H-FIRE treatment with and without calcium.},
   keywords = {Animals
Calcium Chloride/*pharmacology
Cell Death/*drug effects
Cell Line, Tumor
Electroporation/*methods
Humans
Hydrogels
NADPH Oxidases/metabolism
Reactive Oxygen Species/metabolism
Signal Transduction
Calcium
Cell death
Enhanced ablation
High-frequency irreversible electroporation (H-FIRE)
Irreversible electroporation (IRE)
Reversible electroporation},
   ISSN = {1567-5394 (Print)
1567-5394},
   DOI = {10.1016/j.bioelechem.2019.107369},
   year = {2020},
   type = {Journal Article}
}

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