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      Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy

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          Abstract

          Osteosarcoma is the most common primary bone tumor, and its first line of treatment presents a high failure rate. The 5-year survival for children and teenagers with osteosarcoma is 70% (if diagnosed before it has metastasized) or 20% (if spread at the time of diagnosis), stressing the need for novel therapies. Recently, cold atmospheric plasmas (ionized gases consisting of UV–Vis radiation, electromagnetic fields and a great variety of reactive species) and plasma-treated liquids have been shown to have the potential to selectively eliminate cancer cells in different tumors through an oxidative stress-dependent mechanism. In this work, we review the current state of the art in cold plasma therapy for osteosarcoma. Specifically, we emphasize the mechanisms unveiled thus far regarding the action of plasmas on osteosarcoma. Finally, we review current and potential future approaches, emphasizing the most critical challenges for the development of osteosarcoma therapies based on this emerging technique.

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          Cisplatin in cancer therapy: molecular mechanisms of action.

          Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects. Copyright © 2014 Elsevier B.V. All rights reserved.
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            Roles of the immune system in cancer: from tumor initiation to metastatic progression

            In this review, Gonzelez et al. provide an update of recent accomplishments, unifying concepts, and futures challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas. The presence of inflammatory immune cells in human tumors raises a fundamental question in oncology: How do cancer cells avoid the destruction by immune attack? In principle, tumor development can be controlled by cytotoxic innate and adaptive immune cells; however, as the tumor develops from neoplastic tissue to clinically detectable tumors, cancer cells evolve different mechanisms that mimic peripheral immune tolerance in order to avoid tumoricidal attack. Here, we provide an update of recent accomplishments, unifying concepts, and future challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas.
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              Increased reactive oxygen species (ROS) production has been detected in various cancers and has been shown to have several roles, for example, they can activate pro-tumourigenic signalling, enhance cell survival and proliferation, and drive DNA damage and genetic instability. Counterintuitively ROS can also promote anti-tumourigenic signalling, initiating oxidative stress-induced tumour cell death. Tumour cells express elevated levels of antioxidant proteins to detoxify elevated ROS levels, establish a redox balance, while maintaining pro-tumourigenic signalling and resistance to apoptosis. Tumour cells have an altered redox balance to that of their normal counterparts and this identifies ROS manipulation as a potential target for cancer therapies. This review discusses the generation and sources of ROS within tumour cells, the regulation of ROS by antioxidant defence systems, as well as the effect of elevated ROS production on their signalling targets in cancer. It also provides an insight into how pro- and anti-tumourigenic ROS signalling pathways could be manipulated in the treatment of cancer.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                23 February 2021
                February 2021
                : 10
                : 4
                : 893
                Affiliations
                [1 ]Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Escola d’Enginyeria Barcelona Est (EEBE), Universitat Politècnica de Catalunya (UPC), 08930 Barcelona, Spain; miguel.mateu@ 123456upc.edu (M.M.-S.); juan.tornin@ 123456upc.edu (J.T.); maria.pau.ginebra@ 123456upc.edu (M.-P.G.)
                [2 ]Barcelona Research Center in Multiscale Science and Engineering, UPC, 08930 Barcelona, Spain
                [3 ]Research Centre for Biomedical Engineering (CREB), UPC, 08034 Barcelona, Spain
                [4 ]Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08034 Barcelona, Spain
                Author notes
                [* ]Correspondence: cristina.canal@ 123456upc.edu ; Tel.: +34-934-017-810
                Author information
                https://orcid.org/0000-0001-5117-6071
                https://orcid.org/0000-0002-7676-3958
                https://orcid.org/0000-0002-4700-5621
                https://orcid.org/0000-0002-3039-7462
                Article
                jcm-10-00893
                10.3390/jcm10040893
                7926371
                33672274
                26357d83-e098-4fe0-a48c-82a7ebff8856
                © 2021 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
                : 25 January 2021
                : 15 February 2021
                Categories
                Review

                osteosarcoma,cold atmospheric plasma,plasma treated liquids,reactive oxygen and nitrogen species,oxidative stress,tumor microenvironment,cancer stem cells

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