Plasma-derived reactive species shape a differentiation profile in human monocytes

Background: Monocyte-derived macrophages are key regulators and producers of reactive oxygen and nitrogen species (ROS/RNS). Pre-clinical and clinical studies suggest that cold physical plasma may be beneficial in the treatment of inflammatory conditions via the release of ROS/RNS. However, it is unknown how plasma treatment affects monocytes and their differentiation profile. Methods: Naïve or phorbol-12-myristate-13-acetate (PMA)-pulsed THP-1 monocytes were exposed to cold physical plasma. The cells were analyzed regarding their metabolic activity as well as flow cytometry (analysis of viability, oxidation, surface marker expression and cytokine secretion) and high content imaging (quantitative analysis of morphology. Results: The plasma treatment affected THP-1 metabolisms, viability, and morphology. Furthermore, a significant modulation CD55, CD69, CD271 surface-expression and increase of inflammatory IL1β, IL6, IL8, and MCP1 secretion was observed upon plasma treatment. Distinct phenotypical changes in THP-1 cells arguing for a differentiation profile were validated in primary monocytes from donor blood. As a functional outcome, plasma-treated monocytes decreased the viability of co-cultured melanoma cells to a greater extent than their non-treated counterparts. Conclusions: Our results suggest plasma-derived ROS/RNS shaped a differentiation profile in human monocytes as evidenced by their increased inflammatory profile (surface marker and cytokines) as well as functional outcome (tumor toxicity). © 2019 by the authors

Cold argon plasma as adjuvant tumour therapy on progressive head and neck cancer: A preclinical study

Investigating cold argon plasma (CAP) for medical applications is a rapidly growing, innovative field of research. The controllable supply of reactive oxygen and nitrogen species through CAP has the potential for utilization in tumour treatment. Maxillofacial surgery is limited if tumours grow on vital structures such as the arteria carotis. Here CAP could be considered as an option for adjuvant intraoperative tumour therapy especially in the case of squamous cell carcinoma of the head and neck. Further preclinical research is necessary to investigate the efficacy of this technology for future clinical applications in cancer treatment. Initially, a variety of in vitro assays was performed on two cell lines that served as surrogate for the squamous cell carcinoma (SCC) and healthy tissue, respectively. Cell viability, motility and the activation of apoptosis in SCC cells (HNO97) was compared with those in normal HaCaT keratinocytes. In addition, induction of apoptosis in ex vivo CAP treated human tissue biopsies of patients with tumours of the head and neck was monitored and compared to healthy control tissue of the same patient. In response to CAP treatment, normal HaCaT keratinocytes differed significantly from their malignant counterpart HNO97 cells in cell motility only whereas cell viability remained similar. Moreover, CAP treatment of tumour tissue induced more apoptotic cells than in healthy tissue that was accompanied by elevated extracellular cytochrome c levels. This study promotes a future role of CAP as an adjuvant intraoperative tumour therapy option in the treatment of head and neck cancer. Moreover, patient-derived tissue explants complement in vitro examinations in a meaningful way to reflect an antitumoral role of CAP. © 2019 by the authors

Medical Gas Plasma Treatment in Head and Neck Cancer—Challenges and Opportunities

Despite progress in oncotherapy, cancer is still among the deadliest diseases in the Western world, emphasizing the demand for novel treatment avenues. Cold physical plasma has shown antitumor activity in experimental models of, e.g., glioblastoma, colorectal cancer, breast carcinoma, osteosarcoma, bladder cancer, and melanoma in vitro and in vivo. In addition, clinical case reports have demonstrated that physical plasma reduces the microbial contamination of severely infected tumor wounds and ulcerations, as is often seen with head and neck cancer patients. These antimicrobial and antitumor killing properties make physical plasma a promising tool for the treatment of head and neck cancer. Moreover, this type of cancer is easily accessible from the outside, facilitating the possibility of several rounds of topical gas plasma treatment of the same patient. Gas plasma treatment of head and neck cancer induces diverse effects via the deposition of a plethora of reactive oxygen and nitrogen species that mediate redox-biochemical processes, and ultimately, selective cancer cell death. The main advantage of medical gas plasma treatment in oncology is the lack of adverse events and significant side effects compared to other treatment modalities, such as surgical approaches, chemotherapeutics, and radiotherapy, making plasma treatment an attractive strategy for the adjuvant and palliative treatment of head and neck cancer. This review outlines the state of the art and progress in investigating physical plasma as a novel treatment modality in the therapy of head and neck squamous cell carcinoma

Medical Gas Plasma Treatment in Head and Neck Cancer—Challenges and Opportunities

Despite progress in oncotherapy, cancer is still among the deadliest diseases in the Western world, emphasizing the demand for novel treatment avenues. Cold physical plasma has shown antitumor activity in experimental models of, e.g., glioblastoma, colorectal cancer, breast carcinoma, osteosarcoma, bladder cancer, and melanoma in vitro and in vivo. In addition, clinical case reports have demonstrated that physical plasma reduces the microbial contamination of severely infected tumor wounds and ulcerations, as is often seen with head and neck cancer patients. These antimicrobial and antitumor killing properties make physical plasma a promising tool for the treatment of head and neck cancer. Moreover, this type of cancer is easily accessible from the outside, facilitating the possibility of several rounds of topical gas plasma treatment of the same patient. Gas plasma treatment of head and neck cancer induces diverse effects via the deposition of a plethora of reactive oxygen and nitrogen species that mediate redox-biochemical processes, and ultimately, selective cancer cell death. The main advantage of medical gas plasma treatment in oncology is the lack of adverse events and significant side effects compared to other treatment modalities, such as surgical approaches, chemotherapeutics, and radiotherapy, making plasma treatment an attractive strategy for the adjuvant and palliative treatment of head and neck cancer. This review outlines the state of the art and progress in investigating physical plasma as a novel treatment modality in the therapy of head and neck squamous cell carcinoma

Cold Atmospheric Pressure Plasma in Wound Healing and Cancer Treatment

Plasma medicine is gaining increasing attention and is moving from basic research into clinical practice. While areas of application are diverse, much research has been conducted assessing the use of cold atmospheric pressure plasma (CAP) in wound healing and cancer treatment—two applications with entirely different goals. In wound healing, a tissue-stimulating effect is intended, whereas cancer therapy aims at killing malignant cells. In this review, we provide an overview of the latest clinical and some preclinical research on the efficacy of CAP in wound healing and cancer therapy. Furthermore, we discuss the current understanding of molecular signaling mechanisms triggered by CAP that grant CAP its antiseptic and tissue regenerating or anti-proliferative and cell death-inducing properties. For the efficacy of CAP in wound healing, already substantial evidence from clinical studies is available, while evidence for therapeutic effects of CAP in oncology is mainly from in vitro and in vivo animal studies. Efforts to elucidate the mode of action of CAP suggest that different components, such as ultraviolet (UV) radiation, electromagnetic fields, and reactive species, may act synergistically, with reactive species being regarded as the major effector by modulating complex and concentration-dependent redox signaling pathways

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Molecular mechanisms of the efficacy of cold atmospheric pressure plasma (CAP) in cancer treatment

Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Development of a passive navigation principle for the MRI-guided retrograde drilling of osteochondral lesions of the lower limb

Das arthroskopische Débridement in Form minimal-invasiver Anbohrung des Nekroseareals der Osteochondrosis Dissecans stellt eine etablierte und weit verbreitete operative Methode dar. Die exakte Anbohrung setzt jedoch die intraoperativ eindeutige Identifizierung der Läsion durch Arthroskopie und/oder Fluoroskopie voraus. In frühen Stadien und bei intaktem Gelenkknorpel über der Defektzone ist eine zweifelsfreie Visualisierung der Osteonekrose nur durch hochauflösende Schnittbildgebung möglich. MRT-navigierte Operationstechniken stellen für Chirurgen und interventionell-tätige Radiologen ein interessantes und stetig wachsendes Anwendungsfeld dar. Im Rahmen dieser Studie soll ein passives Navigationsverfahren für MRT- kontrollierte Interventionen im Muskuloskelettalbereich vorgestellt und dessen Praktikabilität und Präzision am Beispiel der retrograden Anbohrung osteochondraler Läsionen des Talus und des Kniegelenkes evaluiert werden. Zur Etablierung einer auf MRT-Bildgebung basierenden Technik der retrograden Anbohrung wurde ein Navigationsverfahren entwickelt und an humanen Präparaten von Körperspendern evaluiert. Für diese Methode wurde ein Zielinstrument entworfen, welches die Eigenschaft des MRT als Schnittbildverfahren für die Navigation nutzt. An 16 anatomischen Fuß- und 6 Kniepräparaten wurde eine 4.5 mm große osteochondrale Läsion an der medialen Talusschulter bzw. beiden Femurkondylen präpariert und mit Hilfe der passiven Navigationsmethode MRT- fluoroskopisch angebohrt. Die Auswertung der Bohrergebnisse erfolgte unter Verwendung einer radiologischen Befundungssoftware an parallel zum Bohrkanal erhobenen MRT-Datensätzen. Gemessen wurde der Abstand vom Zentrum des Bohrkanals zum Zentrum der Läsion in zur Bohrachse orthogonal verlaufenden Ebenen. Zusätzlich wurden die benötigten Zeiten zum Planen und Durchführen der Navigation sowie des Bohrvorganges erhoben. Alle osteochondralen Läsionen konnten mit Hilfe der entwickelten passiven Navigationsmethode unter MRT- Echtzeitbildgebung mit einer Genauigkeit von 2.0 ± 0.9 mm am Talus und 1.6 ± 0.9 mm am Kniegelenk erreicht werden. Für die Bohrungen am Talus wurden 8.8 ±1.6 min und 14.1 ± 2.2 min an den Femurkondylen benötigt. Statt multipler Korrekturbohrungen war es möglich, das Ziel mit Hilfe der beschriebenen Navigationsmethode in einem Bohrdurchgang zu erreichen. Die Anbohrung osteochondraler Läsionen unter MRT-fluoroskopischer Bildgebung ist mit hoher Genauigkeit möglich. Das entwickelte passive Navigationskonzept auf Basis eines MRT-kompatiblen Zielinstrumentariums stellt bei der Behandlung der Osteochondrosis Dissecans eine Alternative zu herkömmlichen Methoden der Bildgebung und Navigation während des Eingriffes dar.Arthroscopic drilling is an effective and minimally invasive treatment. However, in early stages, the cartilage layer is intact, and the lesions may not be seen at arthroscopy. Of late, computer-assisted surgery has become a novel challenge for orthopedic surgeons. However, for orthopedic interventions magnetic resonance (MR) fluoroscopy is in its early stages of development. The objective of this study was the development of an innovative passive navigation concept, which is potentially applicable for many magnetic resonance image (MRI)-guided musculoskeletal interventions. The developed method was mainly evaluated in retrograde drilling of artifcial osteochondral lesions of the ankle and knee joint as an example of difficult navigation in drill placement due to poor visualization with X-ray and complex anatomy. To accomplish this objective, a passive navigation device was constructed and evaluated in 16 cadaveric ankle joint specimens and 6 cadaveric knee joint specimens. In each specimen, a cylindrical plug (4.5 mm in diameter) were drilled for simulation of an osteochondral lesion. Feasibility and accuracy of navigated drillings were evaluated. Drillings could be performed with an accuracy of 2.0 ± 0.9 mm (talus) and 1.6 ± 0.9 mm (knee). The time for the navigation and drilling procedures were 8.8 ±1.6 min (talus) and 14.1 ± 2.2 min (knee). Use of this interactive MR-assisted navigation method in combination with a passive aiming device allowed precise and rapid retrograde drilling of osteochondral lesions

Wie können öffentliche E-Ladestationen sozial fair positioniert werden? Eine Analyse der Aktivitätsmuster und potenziellen Ladevorgänge von Frauen, Personen mit niedrigem Einkommen und Über-65-Jährigen

Der Ausbau der Elektromobilität ist ein Weg hin zu einem umweltfreundlicheren Verkehrskonzept. Bei der Erweiterung der E-Ladeinfrastruktur sollte auf die Bedürfnisse von bereits benachteiligten Gruppen eingegangen werden, um Ungerechtigkeiten im zukünftigen Verkehrsmodell zu meiden. In dieser Arbeit wird das Ladeverhalten von Frauen, Personen mit geringem Einkomen und über-65-Jährigen als mögliche benachteiligte Gruppen untersucht. Grundlage dafür ist die Fragestellung, wo ein Laden innerhalb des Aktivitätenverlaufes und den damit verbundenen Aufenthaltsdauern möglich ist. Bei der Geschlechterbetrachtung zeigten sich deutliche Unterschiede in der Weglänge und dem Wegzweck. Auf Basis einer Kurzbefragung wurden zusätzlich die Stellplatzverfügbarkeit an Wohnort und Arbeitsplatz sowie die Bereitschaft zur Verlängerung des Aufenthalts an einem Ort, um Laden zu können, erhoben. Darauf aufbauend wurden zwei synthetische Ladeszenarien definiert, die sich durch verbesserte Fahrzeugtechnik und E-Ladeinfrastruktur unterscheiden um einerseits die Unterschiede für die benachteiligten Gruppen darstellen zu können, und andererseits die Robustheit der Aussagen auch für zukünftige Entwicklungen zu überprüfen. Das Aktivitätsmuster nach Geschlecht und Einkommen wird analysiert, um den idealen Ladevorgang räumlich, wie auch zeitlich in die jeweiligen Aktivitätsmuster einordnen zu können. Es zeigt sich, dass das Laden am privaten Stellplatz am Wohnort den Ladebarf am besten abdecken würde. Hier sind jedoch die betrachteten Gruppen benachteiligt und erhöhen so die Nachfrage an öffentlicher Ladeinfrastruktur in der Nähe von Einkaufsmöglichkeiten und Freizeitstandorten