Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues

Introduction: Medical gas plasma therapy has been successfully applied to several types of cancer in preclinical models. First palliative tumor patients suffering from advanced head and neck cancer benefited from this novel therapeutic modality. The gas plasma-induced biological effects of reactive...

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Main Authors: Nadine Gelbrich, Lea Miebach, Julia Berner, Eric Freund, Fariba Saadati, Anke Schmidt, Matthias Stope, Uwe Zimmermann, Martin Burchardt, Sander Bekeschus
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Journal of Advanced Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2090123222001667
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author Nadine Gelbrich
Lea Miebach
Julia Berner
Eric Freund
Fariba Saadati
Anke Schmidt
Matthias Stope
Uwe Zimmermann
Martin Burchardt
Sander Bekeschus
author_facet Nadine Gelbrich
Lea Miebach
Julia Berner
Eric Freund
Fariba Saadati
Anke Schmidt
Matthias Stope
Uwe Zimmermann
Martin Burchardt
Sander Bekeschus
author_sort Nadine Gelbrich
collection DOAJ
description Introduction: Medical gas plasma therapy has been successfully applied to several types of cancer in preclinical models. First palliative tumor patients suffering from advanced head and neck cancer benefited from this novel therapeutic modality. The gas plasma-induced biological effects of reactive oxygen and nitrogen species (ROS/RNS) generated in the plasma gas phase result in oxidation-induced lethal damage to tumor cells. Objectives: This study aimed to verify these anti-tumor effects of gas plasma exposure on urinary bladder cancer. Methods: 2D cell culture models, 3D tumor spheroids, 3D vascularized tumors grown on the chicken chorion-allantois-membrane (CAM) in ovo, and patient-derived primary cancer tissue gas plasma-treated ex vivo were used. Results: Gas plasma treatment led to oxidation, growth retardation, motility inhibition, and cell death in 2D and 3D tumor models. A marked decline in tumor growth was also observed in the tumors grown in ovo. In addition, results of gas plasma treatment on primary urothelial carcinoma tissues ex vivo highlighted the selective tumor-toxic effects as non-malignant tissue exposed to gas plasma was less affected. Whole-transcriptome gene expression analysis revealed downregulation of tumor-promoting fibroblast growth factor receptor 3 (FGFR3) accompanied by upregulation of apoptosis-inducing factor 2 (AIFm2), which plays a central role in caspase-independent cell death signaling. Conclusion: Gas plasma treatment induced cytotoxicity in patient-derived cancer tissue and slowed tumor growth in an organoid model of urinary bladder carcinoma, along with less severe effects in non-malignant tissues. Studies on the potential clinical benefits of this local and safe ROS therapy are awaited.
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spelling doaj.art-6b3afc09b8cc48da82adf668ec2ca0622023-04-28T08:55:18ZengElsevierJournal of Advanced Research2090-12322023-05-0147209223Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissuesNadine Gelbrich0Lea Miebach1Julia Berner2Eric Freund3Fariba Saadati4Anke Schmidt5Matthias Stope6Uwe Zimmermann7Martin Burchardt8Sander Bekeschus9Clinic and Policlinic for Urology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany; ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, GermanyZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; Clinic and Policlinic for General, Visceral, Thoracic, and Vascular Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; Clinic and Policlinic for Oral, Maxillofacial, and Plastic Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; Clinic and Policlinic for General, Visceral, Thoracic, and Vascular Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; Clinic and Policlinic of Dermatology and Venerology, Rostock University Medical Center, Stempelstr. 13, 18057 Rostock, GermanyZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, GermanyDepartment of Gynecology and Gynecological Oncology, University Hospital Bonn, 53127 Bonn, GermanyClinic and Policlinic for Urology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyClinic and Policlinic for Urology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; Corresponding author.Introduction: Medical gas plasma therapy has been successfully applied to several types of cancer in preclinical models. First palliative tumor patients suffering from advanced head and neck cancer benefited from this novel therapeutic modality. The gas plasma-induced biological effects of reactive oxygen and nitrogen species (ROS/RNS) generated in the plasma gas phase result in oxidation-induced lethal damage to tumor cells. Objectives: This study aimed to verify these anti-tumor effects of gas plasma exposure on urinary bladder cancer. Methods: 2D cell culture models, 3D tumor spheroids, 3D vascularized tumors grown on the chicken chorion-allantois-membrane (CAM) in ovo, and patient-derived primary cancer tissue gas plasma-treated ex vivo were used. Results: Gas plasma treatment led to oxidation, growth retardation, motility inhibition, and cell death in 2D and 3D tumor models. A marked decline in tumor growth was also observed in the tumors grown in ovo. In addition, results of gas plasma treatment on primary urothelial carcinoma tissues ex vivo highlighted the selective tumor-toxic effects as non-malignant tissue exposed to gas plasma was less affected. Whole-transcriptome gene expression analysis revealed downregulation of tumor-promoting fibroblast growth factor receptor 3 (FGFR3) accompanied by upregulation of apoptosis-inducing factor 2 (AIFm2), which plays a central role in caspase-independent cell death signaling. Conclusion: Gas plasma treatment induced cytotoxicity in patient-derived cancer tissue and slowed tumor growth in an organoid model of urinary bladder carcinoma, along with less severe effects in non-malignant tissues. Studies on the potential clinical benefits of this local and safe ROS therapy are awaited.http://www.sciencedirect.com/science/article/pii/S2090123222001667ApoptosisCancerCold physical plasmaOncologyReactive oxygen and nitrogen speciesUrology
spellingShingle Nadine Gelbrich
Lea Miebach
Julia Berner
Eric Freund
Fariba Saadati
Anke Schmidt
Matthias Stope
Uwe Zimmermann
Martin Burchardt
Sander Bekeschus
Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues
Journal of Advanced Research
Apoptosis
Cancer
Cold physical plasma
Oncology
Reactive oxygen and nitrogen species
Urology
title Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues
title_full Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues
title_fullStr Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues
title_full_unstemmed Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues
title_short Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues
title_sort medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient derived tumor tissues
topic Apoptosis
Cancer
Cold physical plasma
Oncology
Reactive oxygen and nitrogen species
Urology
url http://www.sciencedirect.com/science/article/pii/S2090123222001667
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