Preclinical evaluation of an endoscopic electroporation system

Forde, Patrick F.; Sadadcharam, Mira; Bourke, Michael; Conway, Thomas A.; Guerin, Shane R.; Kruijf, Marcel de; O’Sullivan, Gerald C.; Impellizeri, Joseph A.; Clover, A. James P.; Soden, Declan M.

doi:10.1055/s-0042-101343

Cited by 16 publications

(8 citation statements)

References 11 publications

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“…The third large area of preclinical research is dealing with different types of electrodes that can be used in vitro, in vivo, or in humans, that is, grid, single needle, or endoscopic, [59][60][61][62][63][64] with different types (e.g., sine wave pulses, pulsed electromagnetic field, and high-frequency short bipolar pulses), and parameters of electric pulses (amplitude and frequency). [65][66][67][68][69] The overall aim of these studies is to provide new electrodes that will be able to reach/treat the tumors that are not accessible with the current electrodes that are on the market and to provide electrodes that will not induce pain, muscle contraction, and/or skin burns, that is, undesired side effects that are commonly reported in clinical studies on electrochemotherapy.…”

Section: Electrochemotherapy: New Electrodes and Numerical Modelingmentioning

confidence: 99%

Recent Advances in Electrochemotherapy

Čemažar

Serša

2019

Bioelectricity

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Electrochemotherapy is gaining recognition as an effective local therapy that uses systemically or intratumorally injected bleomycin or cisplatin with electroporation as a delivery system that brings drugs into the cells to exert their cytotoxic effects. Preclinical work is still ongoing, testing new drugs, seeking the best treatment combination with other treatment modalities, and exploring new sets of pulses for effective tissue electroporation. The applications of electrochemotherapy are being fully exploited in veterinary oncology, where electrochemotherapy, because of its simple execution, has a relatively good cost-benefit ratio and is used in the treatment of cutaneous tumors. In human oncology, electrochemotherapy is fully recognized as a local therapy for cutaneous tumors and metastases. Its effectiveness is being explored in combination with immunomodulatory drugs. However, the development of electrochemotherapy is directed into the treatment of deepseated tumors with a percutaneous approach. Because of the vast number of reports, this review discusses the articles published in the past 5 years.

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Section: Electrochemotherapy: New Electrodes and Numerical Modelingmentioning

confidence: 99%

Recent Advances in Electrochemotherapy

Čemažar

Serša

2019

Bioelectricity

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“…There are many perspectives of this potential novel anticancer treatment as electroporation-based treatments are increasingly used for treatment of cutaneous metastases (9,10,12) and under investigations for use in internal organs such as brain, liver, and bone metastases (40)(41)(42)(43). Treatment with electric pulses using other parameters than described in this study is also increasingly used, such as irreversible electroporation (44)(45)(46) and nanosecond pulse electric fields (47-49) where addition of calcium might also increase the effect and/or treatment area.…”

Section: Plasma Membrane Calcium Atpase Content In Vitromentioning

confidence: 99%

Normal and Malignant Cells Exhibit Differential Responses to Calcium Electroporation

et al. 2017

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Calcium electroporation may offer a simple general tool for anticancer therapy. Transient permeabilization of cancer cell membranes created by applying short, high-voltage pulses in tumors enables high calcium influxes that trigger cell death. In this study, we compared the relative sensitivity of different human tumor models and normal tissues to calcium electroporation. Plasma membrane Ca-ATPase (PMCA) protein expression was confirmed in all cancer cell lines and normal primary dermal fibroblasts studied. In all tumor types tested, calcium electroporation effectively induced necrosis, with a range of sensitivities observed (36%-88%) 2 days after treatment. Necrosis was induced using calcium concentrations of 100-500 mmol/L and injection volumes 20%-80% of tumor volume. Notably, only limited effects were seen in normal tissue. Calcium content increased >7-fold in tumor and skin tissue after calcium electroporation but decreased in skin tissue 4 hours after treatment to levels comparable with untreated controls, whereas calcium content endured at high levels in tumor tissue. Mechanistic experiments indicated that calcium influx was similar in fibroblasts and cancer cells. However, we observed decreased PMCA expression in cancer cells compared with fibroblasts, offering a potential explanation for the different calcium content in tumor cells versus normal tissues. Overall, our results suggest that calcium electroporation can elicit a rapid and selective necrosis of solid tumors, with limited deleterious effects on surrounding normal tissues..

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“…Electrochemotherapy is in clinical use for cutaneous tumors [10–16], and in development or clinical trials for tumors situated in e.g. bone [17], pancreas [18], brain [17], the colon/rectum [19], as well as head- and neck cancers [20]. Irreversible electroporation [21–23] is also used clinically, and with this technology permeabilization of the cell membrane is much more pronounced, so that tumor cells are extensively permeabilized, leading to cell death associated with loss of ionic homeostasis, and energy depletion.…”

Section: Introductionmentioning

confidence: 99%

Effect of calcium electroporation in combination with metformin in vivo and correlation between viability and intracellular ATP level after calcium electroporation in vitro

Frandsen

Gehl

2017

PLoS ONE

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BackgroundCalcium electroporation is a new experimental anti-cancer treatment where calcium is internalized into cells by application of short, high voltage pulses. Calcium electroporation has been shown to induce tumor necrosis associated with ATP depletion while the effect on normal fibroblasts was limited when investigated in a 3D in vitro spheroid model. We aimed to investigate the effect of calcium electroporation in combination with metformin, a drug that affects intracellular ATP level. We also aimed to study the relationship between the viability and intracellular ATP levels after calcium electroporation in vitro.MethodsIn this study, we investigated the effect of calcium electroporation with metformin on NMRI-Foxn1nu mice in vivo on tumor size, survival, and intracellular ATP. We further investigated viability and intracellular ATP level in vitro after calcium electroporation in two human cancer cell lines: Breast (MDA-MB231) and colon (HT29), and in normal human fibroblasts (HDF-n), as well as investigating viability in human bladder cancer cells (SW780) and human small cell lung cancer cells (H69) where we have previously published intracellular ATP levels.ResultsCalcium electroporation significantly reduced the size and ATP level of bladder cancer tumors treated in vivo but no increased effect of metformin combined with calcium electroporation was shown on neither tumor size, survival, nor ATP level. Calcium electroporation in vitro significantly decreased viability compared with calcium alone (p<0.0001 for calcium concentrations from 0.5 mM for H69, HDF-n, and MDA-MB231; p<0.0001 for calcium concentrations from 1 mM for HT29 and SW780). Intracellular ATP levels decreased significantly after calcium electroporation (p<0.05), however no correlation between intracellular ATP level and viability after treatment was observed.ConclusionCalcium electroporation caused reduced tumor size, increased survival, and acute ATP depletion in vivo. This effect was not augmented by metformin. Calcium electroporation is a possible novel anti-cancer treatment that has been shown to cause cell death associated with acute ATP depletion in vitro and in vivo.

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Preclinical evaluation of an endoscopic electroporation system

Abstract: Electroporation via the new device in combination with bleomycin offers a nonthermal tumor ablative approach, and presents clinicians with a new option for the management of gastrointestinal cancers.

Cited by 16 publications

References 11 publications

Recent Advances in Electrochemotherapy

Recent Advances in Electrochemotherapy

Normal and Malignant Cells Exhibit Differential Responses to Calcium Electroporation

Effect of calcium electroporation in combination with metformin in vivo and correlation between viability and intracellular ATP level after calcium electroporation in vitro

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