###### Abstract  
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 intratumoral role of CAP. Keywords:cold argon plasma; head and neck squamous cell carcinoma; apoptosis; keratinocytes; plasma medicine +
Footnote †: journal: Applied  
therapy for most of the extra- and intraoral tumours is based on a radical surgery combined with stage-based neo-adjuvant and / or adjuvant chemotherapy or radiation. Yet to date, patients suffering from advanced head and neck cancer are still faced with a poor prognosis, if cancer cells are infiltrating sensitive anatomical structures such as the skull base, the ocular bulb or main arteries that cannot be resected safely (one example is given in Figure 1). To reduce chemotherapy side effects and improve clinical outcomes, additional intraoperative antitumor treatment tools are urgently needed to complement current therapies. Cold atmospheric pressure plasma (CAP) at temperatures within physiological ranges offers versatile options for biological and medical applications in general [2; 3; 4; 5] and recently was promoted to aid in cancer therapy [6; 7; 8; 9]. Plasma is often referred to as the fourth state of matter and is considered the most reactive one. Therapeutic effects are achieved in a single treatment modality due to the combined action of ultraviolet radiation, charged particles, reactive oxygen species (ROS), reactive nitrogen species (RNS) and electrical fields [2; 10]. First results on the compatibility and application of CAP were gained in the field of dermatology as well as in plastic and aesthetic medicine [11; 12; 13; 14; 15; 16; 17]. CAP applications can range from anti-inflammatory [18] and antimicrobial [19; 20] to tissue stimulatory [21] therapeutic effects. In addition, recently [PERSON] et al. and others have shown that CAP can inhibit tumour growth by ROS-mediated apoptosis [6; 22; 23]. Moreover, there are indications that CAP works selective for cancer cells by killing them more effectively than non-neoplastic cells [24; 25]. Consequently, the concept of using CAP in the manner of intra-operative neo-adjuvant tumour therapy is to treat remaining cancer cells after conventionally tumour bulk reduction by surgery as far as possible. Hence, CAP offers the potential for new adjuvant tumour therapies [6; 8].