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    Plasma, cancer, immunity
    (Bristol : IOP Publ., 2022) Bekeschus, Sander; Clemen, Ramona
    Albeit heavily investigated for several decades already, the importance of the immune system in targeting cancer has received wide clinical attention only in recent years. This is partly because of long-standing rather traditional concepts on tumor biology on the one hand and the complexity of the immune system and its processes on the other. The viewpoint of evaluating existing and emerging approaches in oncology based on toxicity to tumors and the ability to engage antitumor-immunity is gaining ground across several disciplines. Along those lines, cold physical plasma was suggested as potential anticancer tool more than a decade ago, but solid evidence of the immune system playing a role in plasma cancer treatment only emerged in recent years. Moreover, plasma may support cancer immunotherapies in the future. Cancer immunotherapies are systemic treatments with biologicals that were reported to synergize with existing local physical modalities before, such as radiotherapy and photodynamic therapy. This review outlines key concepts in oncology, immunology, and tumor therapy, links them to plasma research, and discusses immuno-oncological consequences. Finally, promising future clinical applications are summarized. Synoptically, first scientific evidence supports an immuno-oncological dimension of plasma cancer treatment in selected instances, but robust clinical evidence is still lacking. More basic and clinical research is needed to determine the immuno-molecular mechanisms and detailed plasma application modalities to facilitate real patient benefit in the long term.
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    Therapeutic ROS and Immunity in Cancer-The TRIC-21 Meeting
    (Basel : MDPI, 2021) Bekeschus, Sander; Emmert, Steffen; Clemen, Ramona; Boeckmann, Lars
    The first Therapeutic ROS and Immunity in Cancer (TRIC) meeting was organized by the excellence research center ZIK plasmatis (with its previous Frontiers in Redox Biochemistry and Medicine (FiRBaM) and Young Professionals' Workshop in Plasma Medicine (YPWPM) workshop series in Northern Germany) and the excellence research program ONKOTHER-H (Rostock/Greifswald, Germany). The meeting showcased cutting-edge research and liberated discussions on the application of therapeutic ROS and immunology in cancer treatment, primarily focusing on gas plasma technology. The 2-day hybrid meeting took place in Greifswald and online from 15-16 July 2021, facilitating a wide range of participants totaling 66 scientists from 12 countries and 5 continents. The meeting aimed at bringing together researchers from a variety of disciplines, including chemists, biochemists, biologists, engineers, immunologists, physicists, and physicians for interdisciplinary discussions on using therapeutic ROS and medical gas plasma technology in cancer therapy with the four main sessions: "Plasma, Cancer, Immunity", "Plasma combination therapies", "Plasma risk assessment and patients studies", and "Plasma mechanisms and treated liquids in cancer". This conference report outlines the abstracts of attending scientists submitted to this meeting.
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    Plasma-Treated Solutions (PTS) in Cancer Therapy
    (Basel : MDPI, 2021) Tanaka, Hiromasa; Bekeschus, Sander; Yan, Dayun; Hori, Masaru; Keidar, Michael; Laroussi, Mounir
    Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to the toxic action of PTSs, suggesting a broad mechanism of action based on the tumor-toxic activity of ROS/RNS stored in these solutions. Moreover, it is indi-cated that the PTS has immuno-stimulatory properties. Two different routes of application are cur-rently envisaged in the clinical setting. One is direct injection into the bulk tumor, and the other is lavage in patients suffering from peritoneal carcinomatosis adjuvant to standard chemotherapy. While many promising results have been achieved so far, several obstacles, such as the standardized generation of large volumes of sterile PTS, remain to be addressed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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    The Anticancer Efficacy of Plasma-Oxidized Saline (POS) in the Ehrlich Ascites Carcinoma Model In Vitro and In Vivo
    (Basel : MDPI, 2021) Brito, Walison Augusto Silva; Freund, Eric; Nascimento, Thiago Daniel Henrique do; Pasqual-Melo, Gabriella; Sanches, Larissa Juliani; Dionísio, Joyce Hellen Ribeiro; Fumegali, William Capellari; Miebach, Lea; Cecchini, Alessandra Lourenço; Bekeschus, Sander
    Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to oxidize liquids. Saline is a clinically accepted liquid, and here we explored the suitability of plasma-oxidized saline (POS) as anticancer agent technology in vitro and in vivo using the Ehrlich Ascites Carcinoma (EAC) model. EAC mainly grows as a suspension in the peritoneal cavity of mice, making this model ideally suited to test POS as a putative agent against peritoneal carcinomatosis frequently observed with colon, pancreas, and ovarium metastasis. Five POS injections led to a reduction of the tumor burden in vivo as well as in a decline of EAC cell growth and an arrest in metabolic activity ex vivo. The treatment was accompanied by a decreased antioxidant capacity of Ehrlich tumor cells and increased lipid oxidation in the ascites supernatants, while no other side effects were observed. Oxaliplatin and hydrogen peroxide were used as controls and mediated better and worse outcomes, respectively, with the former but not the latter inducing profound changes in the inflammatory milieu among 13 different cytokines investigated in ascites fluid. Modulation of inflammation in the POS group was modest but significant. These results promote POS as a promising candidate for targeting peritoneal carcinomatosis and malignant ascites and suggest EAC to be a suitable and convenient model for analyzing innovative POS approaches and combination therapies.