Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

Mercadal, Borja; Beitel-White, Natalie; Aycock, Kenneth N.; Castellví, Quim; Davalos, Rafael V.; Ivorra, Antoni

doi:10.1007/s10439-020-02462-8

Cited by 56 publications

(38 citation statements)

References 53 publications

(59 reference statements)

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“…It would be reasonable to hypothesize that different tissues and cell types, both healthy and malignant, have different responses to electroporation-based technologies and may require altering dosing, treatment parameters, or co-therapies to obtain optimal effects. In fact, a recent study on pancreatic cancer shows differences in cell death mechanisms initiated by IRE and HFIRE with similar parameters (104). Further investigation into these cell death mechanisms among electroporation-based technologies may help tailor these treatments for personalized medicine.…”

Section: Discussionmentioning

confidence: 94%

“…While directly near the electrodes may be temperature dependent, cell death becomes temperature independent in other regions based on minimum heating effects seen in vitro at comparable electric field magnitudes (7). Multiple studies argued that there may be more than one type of cell death mechanism at play, from necrotic cell death to apoptotic-like non-apoptotic cell death (17,(102)(103)(104). These responses could come from differing tissues being predisposed to specific types FIGURE 2 | Regions of cell death within a typical IRE treatment zone vary spatially.…”

Section: Irreversible Electroporation (Ire)mentioning

confidence: 99%

“…Cell death following H-FIRE is considered to be highly similar to IRE. However, pre-clinical studies show that H-FIRE may be eliciting immunologic cell death and pyroptosis in addition to apoptosis and necrosis (8,104). Intriguingly, the use of H-FIRE may allow tuning of cell death with calcium similar to calcium ECT.…”

Section: High-frequency Irreversible Electroporation (H-fire)mentioning

confidence: 99%

See 2 more Smart Citations

Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies

et al. 2020

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New therapeutic strategies and paradigms are direly needed for the treatment of cancer. While the surgical removal of tumors is favored in most cancer treatment plans, resection options are often limited based on tumor localization. Over the last two decades, multiple tumor ablation strategies have emerged as promising stand-alone or combination therapeutic options for patients. These strategies are often employed to treat tumors in areas where surgical resection is not possible or where chemotherapeutics have proven ineffective. The type of cell death induced by the ablation modality is a critical aspect of therapeutic success that can impact the efficacy of the treatment and systemic anti-tumor immune system responses. Electroporation-based ablation technologies include electrochemotherapy, irreversible electroporation, and other modalities that rely on pulsed electric fields to create pores in cell membranes. These pores can either be reversible or irreversible depending on the electric field parameters and can induce cell death either alone or in combination with a therapeutic agent. However, there have been many controversial findings among these technologies as to the cell death type initiated, from apoptosis to pyroptosis. As cell death mechanisms can impact treatment side effects and efficacy, we review the main types of cell death induced by electroporation-based treatments and summarize the impact of these mechanisms on treatment response. We also discuss potential reasons behind the variability of findings such as the similarities between cell death pathways, differences between cell-types, and the variation in electric field strength across the treatment area.

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Section: Discussionmentioning

confidence: 94%

Section: Irreversible Electroporation (Ire)mentioning

confidence: 99%

Section: High-frequency Irreversible Electroporation (H-fire)mentioning

confidence: 99%

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Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies

et al. 2020

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“…However, a non-thermal ablated lesion was caused without evident coagulation necrosis on gross inspection [19,20]. The cell viability, gross pathology, and histopathology show dynamic change post-EP, which varies in different tissues [21]. In general, the tissue damage process caused by EP ends within 24 h, then the repair procedure begins on days 3 to 7 post-EP and is completed within 28 days.…”

Section: Discussionmentioning

confidence: 99%

Physiological and Histopathological Effects of Electroporation Pulse on Stomach of Rats

Zhang

Han

et al. 2020

Preprint

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BackgroundElectroporation pulse (EP) is an emerging tissue ablation technique with widespread potential, including in the treatment of multiple cancer types. However, there is a lack of knowledge about its effect on the physiology and histopathology of stomachs. The aim of this study was to investigate biological effects of EP applied to stomachs of healthy rats on digestive function, serum marker levels, and gastric tissue structure.MethodsNinety male rats were divided into nine groups and examined up to 28 days post-treatment. A single burst of electroporation pulses (500 V, 99 pluses, 1 Hz, 100 μs) was delivered to the stomachs of the rats using a forceps electrode. Gastric emptying, small intestinal transit, and gastric secretion were measured to evaluate digestive function. Levels of serum markers were determined using ELISA. Haematoxylin–eosin, Masson trichrome, and immunofluorescence were performed for histopathological analysis.ResultsNo significant effect on gastric emptying or secretion were found post-EP, whereas the small intestinal transit decreased at 4 h and rapidly recovered to normal on 1-day post-EP. Further, levels of serum markers such as TNF-α and IL-1β changed temporarily in the acute term but soon returned to normal within 28 days. Moreover, histopathological analysis revealed that that the cell death in ablation area occurred immediately post-EP, and the gastric wall scaffold in the ablation region remained intact post-EP.ConclusionsThis study demonstrates the safety and efficacy of EP on the physiology and histopathology of the stomach and lays a foundation for the wider use of this technique in future studies.

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“…They demonstrated that the H-FIRE pulse waveforms at 4000 V/cm did not cause muscle contractions in a rat model, nor did they cause a significant temperature increase. Since then, much work has been done to further explore the use of H-FIRE with various pulse waveforms by computational [3,5], in vitro [6][7][8], ex vivo [9][10][11], and in vivo [12][13][14][15] studies. Sano et al [6] looked at the use of H-FIRE pulse waveforms with a sub-microsecond pulse width (i.e., 0.25-2-0.25 and 0.5-2-0.5) in a pancreatic tumor cell in vitro cell suspension model and showed this modality was effective at causing cell death.…”

Section: Introductionmentioning

confidence: 99%

An in vivo study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones

Zhang

Liu

Fang

et al. 2021

International Journal of Hyperthermia

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Purpose: To examine the ablation zone, muscle contractions, and temperature increases in both rabbit liver and kidney models in vivo for a custom-made high-frequency irreversible electroporation (H-FIRE) generator. Materials and Methods: A total of 18 New Zealand white rabbits were used to investigate five H-FIRE protocols (n ¼ 3 for each protocol) and an IRE protocol (n ¼ 3) for the performance of the designed H-FIRE device in both liver and kidney tissues. The ablation zone was determined by using histological analysis 72 h after treatment. The extent of muscle contractions and temperature change during the application of pulse energy were measured by a commercial accelerometer attached to animals and fiber optic temperature probe inserted into organs with IRE electrodes, respectively. Results: All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues. The area of ablation zone generated in H-FIRE pulse protocols (e.g., 0.3-1 ls, 2000 V, and 90-195 bursts) appears similar to that of IRE protocol (100 ls, 1000 V, and 90 pulses) in both liver and kidney tissues. No significant temperature increase was noticed except for the protocol with the highest pulse energy (e.g., 1 ls, 2000 V, and 180 bursts). Conclusion: Our work serves to complement the current H-FIRE pulse waveforms, which can be optimized to significantly improve the quality of ablation zone in terms of precision for liver and kidney tumors in clinical setting.

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Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

Cited by 56 publications

References 53 publications

Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies

Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies

Physiological and Histopathological Effects of Electroporation Pulse on Stomach of Rats

An in vivo study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones

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