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      Cold Atmospheric Plasma in the Treatment of Osteosarcoma

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          Abstract

          Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.” The current article summarizes the potential of CAP in the treatment of human OS and reviews the underlying molecular mode of action.

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          Most cited references87

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          Apoptosis, oncosis, and necrosis. An overview of cell death.

          The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.
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            Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy

            Background: Plasma is an ionised gas that is typically generated in high-temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. Methods: Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. Results: We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo. It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated. Conclusion: The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.
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              Plasma Chemistry

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                19 September 2017
                September 2017
                : 18
                : 9
                : 2004
                Affiliations
                [1 ]Department of Trauma, Reconstructive Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany; nadine.gelbrich@ 123456online.de (N.G.); matthias.napp@ 123456uni-greifswald.de (M.N.); traumato@ 123456uni-greifswald.de (A.E.)
                [2 ]Department of Trauma and Orthopaedic Surgery, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Warener Str. 7, 12683 Berlin, Germany
                [3 ]Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK plasmatis, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; sander.bekeschus@ 123456inp-greifswald.de
                [4 ]Department of Hygiene and Environmental Medicine, University Medicine Greifswald, Walther-Rathenau-Str. 49a, 17485 Greifswald, Germany; kramer@ 123456uni-greifswald.de
                [5 ]Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany; stopem@ 123456uni-greifswald.de
                Author notes
                [* ]Correspondence: denis.guembel@ 123456uni-greifswald.de ; Tel.: +49-3834-8622541
                Author information
                https://orcid.org/0000-0003-1330-2676
                https://orcid.org/0000-0002-8773-8862
                Article
                ijms-18-02004
                10.3390/ijms18092004
                5618653
                28925941
                fd3a641a-c891-4b7a-9f1b-17ba5155fb5f
                © 2017 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
                : 13 August 2017
                : 14 September 2017
                Categories
                Review

                Molecular biology
                apoptosis,cancer,cap,osteosarcoma,plasma medicine,plasma oncology
                Molecular biology
                apoptosis, cancer, cap, osteosarcoma, plasma medicine, plasma oncology

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