scholarly journals High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity

EBioMedicine ◽  
2019 ◽  
Vol 44 ◽  
pp. 112-125 ◽  
Author(s):  
Veronica M. Ringel-Scaia ◽  
Natalie Beitel-White ◽  
Melvin F. Lorenzo ◽  
Rebecca M. Brock ◽  
Kathleen E. Huie ◽  
...  
2021 ◽  
pp. 108001
Author(s):  
Kelsey R. Murphy ◽  
Kenneth N. Aycock ◽  
Alayna N. Hay ◽  
John H. Rossmeisl ◽  
Rafael V. Davalos ◽  
...  

2020 ◽  
Author(s):  
Rebecca M. Brock ◽  
Natalie Beitel-White ◽  
Melvin F. Lorenzo ◽  
Veronica M. Ringel-Scaia ◽  
Sheryl Coutermarsh-Ott ◽  
...  

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 277-277
Author(s):  
Imran A Siddiqui ◽  
Russell C. Kirks ◽  
Erin H Baker ◽  
Eduardo Latouche ◽  
Matt Dewitt ◽  
...  

277 Background: Irreversible electroporation unlike ablation is excellent in inducing cell death via apoptosis. It, however, has disadvantages of electrical conduction via cardiac and nervous tissue. This results in requiring cardiac monitoring and general anesthesia and paralytics while performing electroporation. We hypothesized a novel high-frequency IRE (H-FIRE) system employing ultra-short bipolar pulses would obviate the need for cardiac synchronization and paralytics while maintaining measurable effect on cell death. Methods: Female swine (55-65Kg) were used. Two H-FIRE electrodes were inserted into the liver (1.5-cm spacing). In the absence of paralytics H-FIRE pulses were delivered (2250V, 2-5-2 pulse configuration) at different on times (100 vs. 200μs) or number of pulses (100 vs. 300). Next electrodes were placed across major hepatic vascular structures and H-FIRE performed. At conclusion tissue was resected and analyzed histologically. Results: 24 H-FIREs were performed (mean ablation time 275 secs). No EKG abnormalities or changes in vital signs were measured during H-FIRE procedures. In 1/24 H-FIREs minor twitching of the rectus abdominis was recorded coinciding with pulse delivery. Histologically, tissues had effective electroporation as evidenced by cell death and caspase activity. Blinded scoring was performed for necrosis and apoptosis. Areas of cell death were predictable. No significant vascular damage or coagulated/thermally-desiccated blood was detected within major vessels following H-FIRE. Conclusions: H-FIRE is a novel way of liver electroporation. It produces predictable cell apoptosis without the requirement of paralytics and alteration of electrocardiographic signals as compared to traditional electroporation, while preserving underlying vascular integrity. Its application in cancer cell death needs to be further studied, but it has a potential for clinical use in targeting tumors with minimal morbidity and associated cardiac and neurologic side effects.


2009 ◽  
Vol 8 (4) ◽  
pp. 289-306 ◽  
Author(s):  
Axel T. Esser ◽  
Kyle C. Smith ◽  
T. R. Gowrishankar ◽  
James C. Weaver

Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism inducing apoptosis, we use a multicellular system model (spatial scale 100 μm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.


2020 ◽  
Vol 131 ◽  
pp. 107369 ◽  
Author(s):  
Elisa M. Wasson ◽  
Nastaran Alinezhadbalalami ◽  
Rebecca M. Brock ◽  
Irving C. Allen ◽  
Scott S. Verbridge ◽  
...  

2017 ◽  
Vol 24 (3) ◽  
pp. 276-283 ◽  
Author(s):  
Imran A. Siddiqui ◽  
Russell C. Kirks ◽  
Eduardo L. Latouche ◽  
Matthew R. DeWitt ◽  
Jacob H. Swet ◽  
...  

Irreversible electroporation (IRE) is a nonthermal ablation modality employed to induce in situ tissue-cell death. This study sought to evaluate the efficacy of a novel high-frequency IRE (H-FIRE) system to perform hepatic ablations across, or adjacent to, critical vascular and biliary structures. Using ultrasound guidance H-FIRE electrodes were placed across, or adjacent to, portal pedicels, hepatic veins, or the gall bladder in a porcine model. H-FIRE pulses were delivered (2250 V, 2-5-2 pulse configuration) in the absence of cardiac synchronization or intraoperative paralytics. Six hours after H-FIRE the liver was resected and analyzed. Nine ablations were performed in 3 separate experimental groups (major vessels straddled by electrodes, electrodes placed adjacent to major vessels, electrodes placed adjacent to gall bladder). Average ablation time was 290 ± 63 seconds. No electrocardiogram abnormalities or changes in vital signs were observed during H-FIRE. At necropsy, no vascular damage, coagulated-thermally desiccated blood vessels, or perforated biliary structures were noted. Histologically, H-FIRE demonstrated effective tissue ablation and uniform induction of apoptotic cell death in the parenchyma independent of vascular or biliary structure location. Detailed microscopic analysis revealed minor endothelial damage within areas subjected to H-FIRE, particularly in regions proximal to electrode insertion. These data indicate H-FIRE is a novel means to perform rapid, reproducible IRE in liver tissue while preserving gross vascular/biliary architecture. These characteristics raise the potential for long-term survival studies to test the viability of this technology toward clinical use to target tumors not amenable to thermal ablation or resection.


Author(s):  
Christopher B. Arena ◽  
Michael B. Sano ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos

Electroporation is a non-linear biophysical mechanism in which the application of an external pulsed electric field leads to an increase in the permeability of cellular membranes. The extent of electroporation is attributed to the induced buildup of charge across the membrane, and consequently, transmembrane potential (TMP). Increasing the TMP has been described to produce various permeabilizing effects, wherein the formation of hydrophilic, aqueous pores becomes energetically favorable [1]. If the pulse parameters are tuned such that the membrane defects are only temporary, and the cell remains viable, the process is termed reversible electroporation. As a cancer therapy, reversible electroporation has been employed to increase the cellular uptake of chemotherapeutic drugs. Irreversible electroporation (IRE) results when membrane defects are permanent, leading to cell death. Recently, IRE has been recognized as an independent means to destroy tumors without the use of adjuvant drugs and prior to the onset of thermal injury [2].


PLoS ONE ◽  
2007 ◽  
Vol 2 (11) ◽  
pp. e1135 ◽  
Author(s):  
Bassim Al-Sakere ◽  
Franck André ◽  
Claire Bernat ◽  
Elisabeth Connault ◽  
Paule Opolon ◽  
...  

2013 ◽  
Vol 37 (1) ◽  
pp. 140-146 ◽  
Author(s):  
Alban Denys ◽  
Yann Lachenal ◽  
Rafael Duran ◽  
Madeleine Chollet-Rivier ◽  
Pierre Bize

Sign in / Sign up

Export Citation Format

Share Document