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    Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants
    (Basel : MDPI, 2018-10-27) Bekeschus, Sander; Freund, Eric; Wende, Kristian; Gandhirajan, Rajesh; Schmidt, Anke
    Increasing numbers of cancer deaths worldwide demand for new treatment avenues. Cold physical plasma is a partially ionized gas expelling a variety of reactive oxygen and nitrogen species, which can be harnesses therapeutically. Plasmas and plasma-treated liquids have antitumor properties in vitro and in vivo. Yet, global response signatures to plasma treatment have not yet been identified. To this end, we screened eight human cancer cell lines to investigate effects of low-dose, tumor-static plasma-treated medium (PTM) on cellular activity, immune-modulatory properties, and transcriptional levels of 22 redox-related genes. With PTM, a moderate reduction of metabolic activity and modest modulation of chemokine/cytokine pattern and markers of immunogenic cell death was observed. Strikingly, the Nuclear factor (erythroid-derived 2)-like 2 (nrf2) target heme oxygenase 1 (hmox1) was upregulated in all cell lines 4 h post PTM-treatment. nrf2 was not changed, but its baseline expression inversely and significantly correlated with hmox1 expression after exposure to PTM. Besides awarding hmox1 a central role with plasma-derived oxidants, we present a transcriptional redox map of 22 targets and chemokine/cytokine secretion map of 13 targets across eight different human tumor cell lines of four tumor entities at baseline activity that are useful for future studies in this field.
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    Medical gas plasma-stimulated wound healing: Evidence and mechanisms
    (Amsterdam [u.a.] : Elsevier, 2021) Bekeschus, Sander; von Woedtke, Thomas; Emmert, Steffen; Schmidt, Anke
    Defective wound healing poses a significant burden on patients and healthcare systems. In recent years, a novel reactive oxygen and nitrogen species (ROS/RNS) based therapy has received considerable attention among dermatologists for targeting chronic wounds. The multifaceted ROS/RNS are generated using gas plasma technology, a partially ionized gas operated at body temperature. This review integrates preclinical and clinical evidence into a set of working hypotheses mainly based on redox processes aiding in elucidating the mechanisms of action and optimizing gas plasmas for therapeutic purposes. These hypotheses include increased wound tissue oxygenation and vascularization, amplified apoptosis of senescent cells, redox signaling, and augmented microbial inactivation. Instead of a dominant role of a single effector, it is proposed that all mechanisms act in concert in gas plasma-stimulated healing, rationalizing the use of this technology in therapy-resistant wounds. Finally, addressable current challenges and future concepts are outlined, which may further promote the clinical utilization, efficacy, and safety of gas plasma technology in wound care in the future.