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Author: Bekeschus, Sander × Author: Wende, Kristian × Subject: ROS ×

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Now showing 1 - 4 of 4
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    Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
    (Amsterdam [u.a.] : Elsevier, 2022) Bekeschus, Sander; Liebelt, Grit; Menz, Jonas; Singer, Debora; Wende, Kristian; Schmidt, Anke
    Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) are well-described agents in physiology and pathology. Chronic inflammation causes incessant H2O2 generation associated with disease occurrences such as diabetes, autoimmunity, and cancer. In cancer, conditioning of the tumor microenvironment, e.g., hypoxia and ROS generation, has been associated with disease outcomes and therapeutic efficacy. Many reports have investigated the roles of the action of H2O2 across many cell lines and disease models. The genes predisposing tumor cell lines to H2O2-mediated demise are less deciphered, however. To this end, we performed in-house transcriptional profiling of 35 cell lines and simultaneously investigated each cell line's H2O2 inhibitory concentration (IC25) based on metabolic activity. More than 100-fold differences were observed between the most resistant and sensitive cell lines. Correlation and gene ontology pathway analysis identified a rigid association with genes intertwined in cell cycle progression and proliferation, as such functional categories dominated the top ten significant processes. The ten most substantially correlating genes (Spearman r > 0.70 or < -0.70) were validated using qPCR, showing complete congruency with microarray analysis findings. Western blotting confirmed the correlation of cell cycle-related proteins negatively correlating with H2O2 IC25. Top genes related to ROS production or antioxidant defense were only modest in correlation (Spearman r > 0.40 or < -0.40). In conclusion, our in-house transcriptomic correlation analysis revealed a set of cell cycle-associated genes associated with a priori resistance or sensitivity to H2O2-induced cellular demise with the detailed and causative roles of individual genes remaining unclear.
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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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    Pancreatic Cancer Cells Undergo Immunogenic Cell Death upon Exposure to Gas Plasma-Oxidized Ringers Lactate
    (Basel : MDPI, 2023) Miebach, Lea; Mohamed, Hager; Wende, Kristian; Miller, Vandana; Bekeschus, Sander
    Survival rates among patients with pancreatic cancer, the most lethal gastrointestinal cancer, have not improved compared to other malignancies. Early tumor dissemination and a supportive, cancer-promoting tumor microenvironment (TME) limit therapeutic options and consequently impede tumor remission, outlining an acute need for effective treatments. Gas plasma-oxidized liquid treatment showed promising preclinical results in other gastrointestinal and gynecological tumors by targeting the tumor redox state. Here, carrier solutions are enriched with reactive oxygen (ROS) and nitrogen (RNS) species that can cause oxidative distress in tumor cells, leading to a broad range of anti-tumor effects. Unfortunately, clinical relevance is often limited, as many studies have forgone the use of medical-grade solutions. This study investigated the efficacy of gas plasma-oxidized Ringer’s lactate (oxRilac), a physiological solution often used in clinical practice, on two pancreatic cancer cell lines to induce tumor toxicity and provoke immunogenicity. Tumor toxicity of the oxRilac solutions was further confirmed in three-dimensional tumor spheroids monitored over 72 h and in ovo using stereomicroscope imaging of excised GFP-expressing tumors. We demonstrated that cell death signaling was induced in a dose-dependent fashion in both cell lines and was paralleled by the increased surface expression of key markers of immunogenic cell death (ICD). Nuclear magnetic resonance (NMR) spectroscopy analysis suggested putative reaction pathways that may cause the non-ROS related effects. In summary, our study suggests gas plasma-deposited ROS in clinically relevant liquids as an additive option for treating pancreatic cancers via immune-stimulating and cytotoxic effects.
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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.