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    Gas Plasma Exposure of Glioblastoma Is Cytotoxic and Immunomodulatory in Patient-Derived GBM Tissue
    (Basel : MDPI, 2022) Bekeschus, Sander; Ispirjan, Mikael; Freund, Eric; Kinnen, Frederik; Moritz, Juliane; Saadati, Fariba; Eckroth, Jacqueline; Singer, Debora; Stope, Matthias B.; Wende, Kristian; Ritter, Christoph A.; Schroeder, Henry W. S.; Marx, Sascha
    Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies. Several experimental studies have suggested gas plasma technology, a partially ionized gas that generates a potent mixture of reactive oxygen species (ROS), as a future complement to the existing treatment arsenal. However, aspects such as immunomodulation, inflammatory consequences, and feasibility studies using GBM tissue have not been addressed so far. In vitro, gas plasma generated ROS that oxidized cells and led to a treatment time-dependent metabolic activity decline and G2 cell cycle arrest. In addition, peripheral blood-derived monocytes were co-cultured with glioblastoma cells, and immunomodulatory surface expression markers and cytokine release were screened. Gas plasma treatment of either cell type, for instance, decreased the expression of the M2-macrophage marker CD163 and the tolerogenic molecule SIGLEC1 (CD169). In patient-derived GBM tissue samples exposed to the plasma jet kINPen ex vivo, apoptosis was significantly increased. Quantitative chemokine/cytokine release screening revealed gas plasma exposure to significantly decrease 5 out of 11 tested chemokines and cytokines, namely IL-6, TGF-β, sTREM-2, b-NGF, and TNF-α involved in GBM apoptosis and immunomodulation. In summary, the immuno-modulatory and proapoptotic action shown in this study might be an important step forward to first clinical observational studies on the future discovery of gas plasma technology’s potential in neurosurgery and neuro-oncology especially in putative adjuvant or combinatory GBM treatment settings.
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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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    Protective role of sphingomyelin in eye lens cell membrane model against oxidative stress
    (Basel : MDPI, 2021) Ravandeh, Mehdi; Coliva, Giulia; Kahlert, Heike; Azinfar, Amir; Helm, Christiane A.; Fedorova, Maria; Wende, Kristian
    In the eye lens cell membrane, the lipid composition changes during the aging process: the proportion of sphingomyelins (SM) increases, that of phosphatidylcholines decreases. To investigate the protective role of the SMs in the lens cell membrane against oxidative damage, analytical techniques such as electrochemistry, high-resolution mass spectrometry (HR-MS), and atomic force microscopy (AFM) were applied. Supported lipid bilayers (SLB) were prepared to mimic the lens cell membrane with different fractions of PLPC/SM (PLPC: 1-palmitoyl-2-linoleoylsn-glycero-3-phosphocholine). The SLBs were treated with cold physical plasma. A protective effect of 30% and 44% in the presence of 25%, and 75% SM in the bilayer was observed, respectively. PLPC and SM oxidation products were determined via HR-MS for SLBs after plasma treatment. The yield of fragments gradually decreased as the SM ratio increased. Topographic images obtained by AFM of PLPC-bilayers showed SLB degradation and pore formation after plasma treatment, no degradation was observed in PLPC/SM bilayers. The results of all techniques confirm the protective role of SM in the membrane against oxidative damage and support the idea that the SM content in lens cell membrane is increased during aging in the absence of effective antioxidant systems to protect the eye from oxidative damage and to prolong lens transparency.
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    X-ray Ptychographic Imaging and Spectroscopic Studies of Plasma-Treated Plastic Films
    (Basel : MDPI, 2022) Ravandeh, Mehdi; Mehrjoo, Masoud; Kharitonov, Konstantin; Schäfer, Jan; Quade, Antje; Honnorat, Bruno; Ruiz-Lopez, Mabel; Keitel, Barbara; Kreis, Svea; Pan, Rui; Gang, Seung-gi; Wende, Kristian; Plönjes, Elke
    Polyethylene terephthalate (PET) is a thermoplastic polyester with numerous applications in industry. However, it requires surface modification on an industrial scale for printing and coating processes and plasma treatment is one of the most commonly used techniques to increase the hydrophilicity of the PET films. Systematic improvement of the surface modification by adaption of the plasma process can be aided by a comprehensive understanding of the surface morphology and chemistry. However, imaging large surface areas (tens of microns) with a resolution that allows understanding the surface quality and modification is challenging. As a proof-of-principle, plasma-treated PET films were used to demonstrate the capabilities of X-ray ptychography, currently under development at the soft X-ray free-electron laser FLASH at DESY, for imaging macroscopic samples. In combination with scanning electron microscopy (SEM), this new technique was used to study the effects of different plasma treatment processes on PET plastic films. The studies on the surface morphology were complemented by investigations of the surface chemistry using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). While both imaging techniques consistently showed an increase in roughness and change in morphology of the PET films after plasma treatment, X-ray ptychography can provide additional information on the three-dimensional morphology of the surface. At the same time, the chemical analysis shows an increase in the oxygen content and polarity of the surface without significant damage to the polymer, which is important for printing and coating processes.