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End date: 2024 × Start date: 2020 × Publisher: Amsterdam [u.a.] : Elsevier × Subject: kINPen ×

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    xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells
    (Amsterdam [u.a.] : Elsevier, 2020) Bekeschus, Sander; Eisenmann, Sebastian; Sagwal, Sanjeev Kumar; Bodnar, Yana; Moritz, Juliane; Poschkamp, Broder; Stoffels, Ingo; Emmert, Steffen; Madesh, Muniswamy; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Gandhirajan, Rajesh Kumar
    Cold physical plasma is a partially ionized gas investigated as a new anticancer tool in selectively targeting cancer cells in monotherapy or in combination with therapeutic agents. Here, we investigated the intrinsic resistance mechanisms of tumor cells towards physical plasma treatment. When analyzing the dose-response relationship to cold plasma-derived oxidants in 11 human cancer cell lines, we identified four 'resistant' and seven 'sensitive' cell lines. We observed stable intracellular glutathione levels following plasma treatment only in the 'resistant' cell lines indicative of altered antioxidant mechanisms. Assessment of proteins involved in GSH metabolism revealed cystine-glutamate antiporter xCT (SLC7A11) to be significantly more abundant in the 'resistant' cell lines as compared to 'sensitive' cell lines. This decisive role of xCT was confirmed by pharmacological and genetic inhibition, followed by cold physical plasma treatment. Finally, microscopy analysis of ex vivo plasma-treated human melanoma punch biopsies suggested a correlation between apoptosis and basal xCT protein abundance. Taken together, our results demonstrate that xCT holds the potential as a biomarker predicting the sensitivity of tumor cells towards plasma treatment.
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    Medical gas plasma promotes blood coagulation via platelet activation
    (Amsterdam [u.a.] : Elsevier, 2021) Bekeschus, Sander; Poschkamp, Broder; van der Linde, Julia
    Major blood loss still is a risk factor during surgery. Electrocauterization often is used for necrotizing the tissue and thereby halts bleeding (hemostasis). However, the carbonized tissue is prone to falling off, putting patients at risk of severe side effects, such as dangerous internal bleeding many hours after surgery. We have developed a medical gas plasma jet technology as an alternative to electrocauterization and investigated its hemostatic (blood clotting) effects and mechanisms of action using whole human blood. The gas plasma efficiently coagulated anticoagulated donor blood, which resulted from the local lysis of red blood cells (hemolysis). Image cytometry further showed enhanced platelet aggregation. Gas plasmas release reactive oxygen species (ROS), but neither scavenging of long-lived ROS nor addition of chemically-generated ROS were able to abrogate or recapitulate the gas plasma effect, respectively. However, platelet activation was markedly impaired in platelet-rich plasma when compared to gas plasma-treated whole blood that moreover contained significant amounts of hemoglobin indicative of red blood cell lysis (hemolysis). Finally, incubation of whole blood with concentration-matched hemolysates phenocopied the gas plasmas-mediated platelet activation. These results will spur the translation of plasma systems for hemolysis into clinical practice.