Cold Atmospheric Plasma in the Treatment of Osteosarcoma

Gümbel, Denis; Bekeschus, Sander; Gelbrich, Nadine; Napp, Matthias; Ekkernkamp, Axel; Krämer, Axel; Stope, Matthias B.

doi:10.3390/ijms18092004

Cited by 52 publications

(45 citation statements)

References 115 publications

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“…From another point of view, up to now, cytotoxicity of CAPs or plasma-activated media in OS cell lines have been investigated only in adherent cell cultures [22,23,[29][30][31]36,37]. This kind of in vitro models provides limited clinically relevant information.…”

Section: Introductionmentioning

confidence: 99%

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Mateu-Sanz

Tornín

Brulin

et al. 2020

Cancers

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Osteosarcoma (OS) is the main primary bone cancer, presenting poor prognosis and difficult treatment. An innovative therapy may be found in cold plasmas, which show anti-cancer effects related to the generation of reactive oxygen and nitrogen species in liquids. In vitro models are based on the effects of plasma-treated culture media on cell cultures. However, effects of plasma-activated saline solutions with clinical application have not yet been explored in OS. The aim of this study is to obtain mechanistic insights on the action of plasma-activated Ringer’s saline (PAR) for OS therapy in cell and organotypic cultures. To that aim, cold atmospheric plasma jets were used to obtain PAR, which produced cytotoxic effects in human OS cells (SaOS-2, MG-63, and U2-OS), related to the increasing concentration of reactive oxygen and nitrogen species generated. Proof of selectivity was found in the sustained viability of hBM-MSCs with the same treatments. Organotypic cultures of murine OS confirmed the time-dependent cytotoxicity observed in 2D. Histological analysis showed a decrease in proliferating cells (lower Ki-67 expression). It is shown that the selectivity of PAR is highly dependent on the concentrations of reactive species, being the differential intracellular reactive oxygen species increase and DNA damage between OS cells and hBM-MSCs key mediators for cell apoptosis.

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Section: Introductionmentioning

confidence: 99%

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Mateu-Sanz

Tornín

Brulin

et al. 2020

Cancers

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“…Medical gas plasma technology recently gained attention due to its antitumor activity against many types of cancers [4][5][6]. Specifically, plasma was shown to inactivate, for instance, malignant melanoma [7], squamous cell carcinoma [5,8], lung cancer [9], colon cancer [10], pancreatic cancer [11], osteosarcoma [12], glioblastoma [13], and hepatocellular carcinoma [14]. The technology uses electrical discharge to partially ionize a neutral gas, and is designed in a way that it promotes biomedical effects in cells and tissues without thermal harm [15].…”

Section: Introductionmentioning

confidence: 99%

Gas Plasma-Treated Prostate Cancer Cells Augment Myeloid Cell Activity and Cytotoxicity

et al. 2020

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Despite recent improvements in cancer treatment, with many of them being related to foster antitumor immunity, tumor-related deaths continue to be high. Novel avenues are needed to complement existing therapeutic strategies in oncology. Medical gas plasma technology recently gained attention due to its antitumor activity. Gas plasmas act via the local deposition of a plethora of reactive oxygen species (ROS) that promote the oxidative cancer cell death. The immunological consequences of plasma-mediated tumor cell death are only poorly understood, however. To this end, we exposed two prostate cancer cell lines (LNCaP, PC3) to gas plasma in vitro, and investigated the immunomodulatory effects of the supernatants in as well as of direct co-culturing with two human myeloid cell lines (THP-1, HL-60). After identifying the cytotoxic action of the kINPen plasma jet, the supernatants of plasma-treated prostate cancer cells modulated myeloid cell-related mitochondrial ROS production and their metabolic activity, proliferation, surface marker expression, and cytokine release. Direct co-culture amplified differentiation-like surface marker expression in myeloid cells and promoted their antitumor-toxicity in the gas plasma over the untreated control conditions. The results suggest that gas plasma-derived ROS not only promote prostate cancer cell death but also augment myeloid cell activity and cytotoxicity.

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“…Argon was excited within the active plasma zone in the head of the kINPen, and excited argon species were subsequently driven out to the ambient air where they reacted with oxygen and nitrogen to form ROS and RNS. [ 67 ] One cycle of therapy lasted 1 week that included three individual single‐gas plasma applications, followed by 1 week without plasma therapy. For one single‐gas plasma application, the area of the ulcerated tumor was repeatedly exposed to the visible tip of plasma effluent for approximately 1 min/cm 2 .…”

Section: Medical Gas Plasma and Hnsccmentioning

confidence: 99%

Plasma medical oncology: Immunological interpretation of head and neck squamous cell carcinoma

Witzke

Seebauer

Jesse

et al. 2020

Plasma Processes & Polymers

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The prognosis of patients suffering from advanced-stage head and neck squamous cell carcinoma (HNSCC) remains poor. Medical gas plasma therapy receives growing attention as a novel anticancer modality. Our recent prospective observational study on HNSCC patients suffering from contaminated tumor ulcerations without lasting remission after first-line anticancer therapy showed remarkable efficacy of gas plasma treatment, with the ulcerated tumor surface decreasing by up to 80%. However, tumor growth relapsed, and this biphasic response may be a consequence of immunological and molecular changes in the tumor microenvironment that could be caused by (a) immunosuppression, (b) tumor cell adaption, (c) loss of microbe-induced immunostimulation, and/or (d) stromal cell adaption. These considerations may be vital for the design of clinical plasma trials in the future.

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Cold Atmospheric Plasma in the Treatment of Osteosarcoma

Cited by 52 publications

References 115 publications

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Gas Plasma-Treated Prostate Cancer Cells Augment Myeloid Cell Activity and Cytotoxicity

Plasma medical oncology: Immunological interpretation of head and neck squamous cell carcinoma

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