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    Plasma treatment limits cutaneous squamous cell carcinoma development in vitro and in vivo
    (Basel : MDPI AG, 2020) Pasqual-Melo, Gabriella; Nascimento, Thiago; Sanches, Larissa Juliani; Blegniski, Fernanda Paschoal; Bianchi, Julya Karen; Sagwal, Sanjeev Kumar; Berner, Julia; Schmidt, Anke; Emmert, Steffen; Weltmann, Klaus-Dieter; Woedtke, Thomas von; Gandhirajan, Rajesh Kumar; Cecchini, Alessandra Lourenço; Bekeschus, Sander
    Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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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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    Small Molecules in the Treatment of Squamous Cell Carcinomas: Focus on Indirubins
    (Basel : MDPI, 2021) Schäfer, Mirijam; Semmler, Marie Luise; Bernhardt, Thoralf; Fischer, Tobias; Kakkassery, Vinodh; Ramer, Robert; Hein, Martin; Bekeschus, Sander; Langer, Peter; Hinz, Burkhard; Emmert, Steffen; Boeckmann, Lars
    Skin cancers are the most common malignancies in the world. Among the most frequent skin cancer entities, squamous cell carcinoma (SCC) ranks second (~20%) after basal cell carcinoma (~77%). In early stages, a complete surgical removal of the affected tissue is carried out as standard therapy. To treat advanced and metastatic cancers, targeted therapies with small molecule inhibitors are gaining increasing attention. Small molecules are a heterogeneous group of protein regulators, which are produced by chemical synthesis or fermentation. The majority of them belong to the group of receptor tyrosine kinase inhibitors (RTKIs), which specifically bind to certain RTKs and directly influence the respective signaling pathway. Knowledge of characteristic molecular alterations in certain cancer entities, such as SCC, can help identify tumor-specific substances for targeted therapies. Most frequently, altered genes in SCC include TP53, NOTCH, EGFR, and CCND1. For example, the gene CCND1, which codes for cyclin D1 protein, is upregulated in nearly half of SCC cases and promotes proliferation of affected cells. A treatment with the small molecule 5'-nitroindirubin-monoxime (INO) leads to inhibition of cyclin D1 and thus inhibition of proliferation. As a component of Danggui Longhui Wan, a traditional Chinese medicine, indirubins are used to treat chronic diseases and have been shown to inhibit inflammatory reactions. Indirubins are pharmacologically relevant small molecules with proapoptotic and antiproliferative activity. In this review, we discuss the current literature on indirubin-based small molecules in cancer treatment. A special focus is on the molecular biology of squamous cell carcinomas, their alterations, and how these are rendered susceptible to indirubin-based small molecule inhibitors. The potential molecular mechanisms of the efficacy of indirubins in killing SCC cells will be discussed as well.
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    Molecular mechanisms of the efficacy of cold atmospheric pressure plasma (CAP) in cancer treatment
    (Basel : MDPI AG, 2020) Semmler, Marie Luise; Bekeschus, Sander; Schäfer, Mirijam; Bernhardt, Thoralf; Fischer, Tobias; Witzke, Katharina; Seebauer, Christian; Rebl, Henrike; Grambow, Eberhard; Vollmar, Brigitte; Nebe, J. Barbara; Metelmann, Hans-Robert; Woedtke, Thomas von; Emmert, Steffen; Boeckmann, Lars
    Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.