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    Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice
    (Weinheim : Wiley-VCH, 2021) Clemen, Ramona; Freund, Eric; Mrochen, Daniel; Miebach, Lea; Schmidt, Anke; Rauch, Bernhard H.; Lackmann, Jan‐Wilm; Martens, Ulrike; Wende, Kristian; Lalk, Michael; Delcea, Mihaela; Bröker, Barbara M.; Bekeschus, Sander
    Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova. T cells from Ova-specific OT-II but not from C57BL/6 or SKH-1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon-gamma production, a known anti-melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova-expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen-presenting cells when compared to their Ova-vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.
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    Plasma Medicine Technologies
    (Basel : MDPI, 2021) Kaushik, Nagendra Kumar; Bekeschus, Sander; Tanaka, Hiromasa; Lin, Abraham; Choi, Eun Ha
    This Special Issue, entitled “Plasma Medicine Technologies”, covers the latest remarkable developments in the field of plasma bioscience and medicine. Plasma medicine is an interdisciplinary field that combines the principles of plasma physics, material science, bioscience, and medicine, towards the development of therapeutic strategies. A study on plasma medicine has yielded the development of new treatment opportunities in medical and dental sciences. An important aspect of this issue is the presentation of research underlying new therapeutic methods that are useful in medicine, dentistry, sterilization, and, in the current scenario, that challenge perspectives in biomedical sciences. This issue is focused on basic research on the characterization of the bioplasma sources applicable to living cells, especially to the human body, and fundamental research on the mutual interactions between bioplasma and organic–inorganic liquids, and bio or nanomaterials.
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    Lack of Adverse Effects of Cold Physical Plasma-Treated Blood from Leukemia Patients: A Proof-of-Concept Study
    (Basel : MDPI, 2021) Golpour, Monireh; Alimohammadi, Mina; Mohseni, Alireza; Zaboli, Ehsan; Sohbatzadeh, Farshad; Bekeschus, Sander; Rafiei, Alireza
    Chronic lymphocytic leukemia (CLL) is the most common blood malignancy with multiple therapeutic challenges. Cold physical plasma has been considered a promising approach in cancer therapy in recent years. In this study, we aimed to evaluate the cytotoxic effect of cold plasma or plasma-treated solutions (PTS) on hematologic parameters in the whole blood of CLL patients. The mean red blood cell count, white blood cell (WBC) count, platelet and hemoglobin counts, and peripheral blood smear images did not significantly differ between treated and untreated samples in either CLL or healthy individuals. However, both direct plasma and indirect PTS treatment increased lipid peroxidation and RNS deposition in the whole blood of CLL patients and in healthy subjects. In addition, the metabolic activity of WBCs was decreased with 120 s of cold plasma or PTS treatment after 24 h and 48 h. However, cold plasma and PTS treatment did not affect the prothrombin time, partial thromboplastin time, nor hemolysis in either CLL patients or in healthy individuals. The present study identifies the components of cold plasma to reach the blood without disturbing the basic parameters important in hematology, confirming the idea that the effect of cold plasma may not be limited to solid tumors and possibly extends to hematological disorders. Further cellular and molecular studies are needed to determine which cells in CLL patients are targeted by cold plasma or PTS.
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    Antitumor Effects in Gas Plasma-Treated Patient-Derived Microtissues—An Adjuvant Therapy for Ulcerating Breast Cancer?
    (Basel : MDPI, 2021) Akbari, Zahra; Saadati, Fariba; Mahdikia, Hamed; Freund, Eric; Abbasvandi, Fereshteh; Shokri, Babak; Zali, Hakimeh; Bekeschus, Sander
    Despite global research and continuous improvement in therapy, cancer remains a challenging disease globally, substantiating the need for new treatment avenues. Medical gas plasma technology has emerged as a promising approach in oncology in the last years. Several investigations have provided evidence of an antitumor action in vitro and in vivo, including our recent work on plasma-mediated reduction of breast cancer in mice. However, studies of gas plasma exposure on patient-derived tumors with their distinct microenvironment (TME) are scarce. To this end, we here investigated patient-derived breast cancer tissue after gas plasma-treated ex vivo. The tissues were disjoint to pieces smaller than 100 µm, embedded in collagen, and incubated for several days. The viability of the breast cancer tissue clusters and their outgrowth into their gel microenvironment declined with plasma treatment. This was associated with caspase 3-dependent apoptotic cell death, paralleled by an increased expression of the anti-metastatic adhesion molecule epithelial (E)-cadherin. Multiplex chemokine/cytokine analysis revealed a marked decline in the release of the interleukins 6 and 8 (IL-6, IL-8) and monocyte-chemoattractant-protein 1 (MCP) known to promote a cancer-promoting milieu in the TME. In summary, we provide here, for the first time, evidence of a beneficial activity of gas plasma exposure on human patient-derived breast cancer tissue.
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    Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen
    (London : Nature Publishing Group, 2021) Miebach, Lea; Freund, Eric; Horn, Stefan; Niessner, Felix; Sagwal, Sanjeev Kumar; von Woedtke, Thomas; Emmert, Steffen; Weltmann, Klaus-Dieter; Clemen, Ramona; Schmidt, Anke; Gerling, Torsten; Bekeschus, Sander
    Recent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.