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      Oxidative Effects during Irreversible Electroporation of Melanoma Cells—In Vitro Study

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          Abstract

          Irreversible electroporation (IRE) is today used as an alternative to surgery for the excision of cancer lesions. This study aimed to investigate the oxidative and cytotoxic effects the cells undergo during irreversible electroporation using IRE protocols. To do so, we used IRE-inducing pulsed electric fields (PEFs) (eight pulses of 0.1 ms duration and 2–4 kV/cm intensity) and compared their effects to those of PEFs of intensities below the electroporation threshold (eight pulses, 0.1 ms, 0.2–0.4 kV/cm) and the PEFs involving elongated pulses (eight pulses, 10 ms, 0.2–0.4 kV/cm). Next, to follow the morphology of the melanoma cell membranes after treatment with the PEFs, we analyzed the permeability and integrity of their membranes and analyzed the radical oxygen species (ROS) bursts and the membrane lipids’ oxidation. Our data showed that IRE-induced high cytotoxic effect is associated both with irreversible cell membrane disruption and ROS-associated oxidation, which is occurrent also in the low electric field range. It was shown that the viability of melanoma cells characterized by similar ROS content and lipid membrane oxidation after PEF treatment depends on the integrity of the membrane system. Namely, when the effects of the PEF on the membrane are reversible, aside from the high level of ROS and membrane oxidation, the cell does not undergo cell death.

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          Most cited references54

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          Melanoma treatment in review

          Melanoma represents the most aggressive and the deadliest form of skin cancer. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. The therapeutic strategy can include single agents or combined therapies, depending on the patient’s health, stage, and location of the tumor. The efficiency of these treatments can be decreased due to the development of diverse resistance mechanisms. New therapeutic targets have emerged from studies of the genetic profile of melanocytes and from the identification of molecular factors involved in the pathogenesis of the malignant transformation. In this review, we aim to survey therapies approved and under evaluation for melanoma treatment and relevant research on the molecular mechanisms underlying melanomagenesis.
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            Membrane Electroporation and Electropermeabilization: Mechanisms and Models

            Exposure of biological cells to high-voltage, short-duration electric pulses causes a transient increase in their plasma membrane permeability, allowing transmembrane transport of otherwise impermeant molecules. In recent years, large steps were made in the understanding of underlying events. Formation of aqueous pores in the lipid bilayer is now a widely recognized mechanism, but evidence is growing that changes to individual membrane lipids and proteins also contribute, substantiating the need for terminological distinction between electroporation and electropermeabilization. We first revisit experimental evidence for electrically induced membrane permeability, its correlation with transmembrane voltage, and continuum models of electropermeabilization that disregard the molecular-level structure and events. We then present insights from molecular-level modeling, particularly atomistic simulations that enhance understanding of pore formation, and evidence of chemical modifications of membrane lipids and functional modulation of membrane proteins affecting membrane permeability. Finally, we discuss the remaining challenges to our full understanding of electroporation and electropermeabilization.
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              Tumor ablation: common modalities and general practices.

              Tumor ablation is a minimally invasive technique that is commonly used in the treatment of tumors of the liver, kidney, bone, and lung. During tumor ablation, thermal energy is used to heat or cool tissue to cytotoxic levels (less than -40°C or more than 60°C). An additional technique is being developed that targets the permeability of the cell membrane and is ostensibly nonthermal. Within the classification of tumor ablation, there are several modalities used worldwide: radiofrequency, microwave, laser, high-intensity focused ultrasound, cryoablation, and irreversible electroporation. Each technique, although similar in purpose, has specific and optimal indications. This review serves to discuss general principles and technique, reviews each modality, and discusses modality selection. © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                31 December 2020
                January 2021
                : 26
                : 1
                : 154
                Affiliations
                [1 ]Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; Wojciech.Szlasa@ 123456outlook.com (W.S.); Aleksander.Kielbik@ 123456outlook.com (A.K.)
                [2 ]Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland; A.Szewczyk@ 123456umed.wroc.pl (A.S.); Nina.Rembialkowska@ 123456umed.wroc.pl (N.R.); Jolanta.Saczko@ 123456umed.wroc.pl (J.S.)
                [3 ]Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wroclaw, 50-328 Wroclaw, Poland
                [4 ]Faculty of Electronics, Vilnius Gediminas Technical University, 03227 Vilnius, Lithuania; Vitalij.Novickij@ 123456vgtu.lt
                [5 ]Université de Lorraine, CNRS, LPCT, F-54000 Nancy, France; Mounir.Tarek@ 123456univ-lorraine.fr
                Author notes
                [* ]Correspondence: Julita.Kulbacka@ 123456umed.wroc.pl ; Tel.: +48-71-784-06-88
                Author information
                https://orcid.org/0000-0002-5477-5771
                https://orcid.org/0000-0001-6828-6138
                https://orcid.org/0000-0001-9435-9409
                https://orcid.org/0000-0001-5273-5293
                https://orcid.org/0000-0001-8272-5440
                Article
                molecules-26-00154
                10.3390/molecules26010154
                7796376
                33396317
                6c840de4-be71-4c84-bef0-11ef896bfdc9
                © 2020 by the authors.

                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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 November 2020
                : 28 December 2020
                Categories
                Article

                ire,oxidative stress,melanoma,permeabilization,membrane alternations

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