Kim Rouven Liedtke

Non-thermal plasma-treated solution demonstrates antitumor activity against pancreatic cancer cells in vitro and in vivo

Pancreatic cancer is associated with a high mortality rate. In advanced stage, patients often experience peritoneal carcinomatosis. Using a syngeneic murine pancreatic cancer cell tumor model, the effect of non-thermal plasma (NTP) on peritoneal metastatic lesions was studied. NTP generates reactive species of several kinds which have been proven to be of relevance in cancer. In vitro, exposure to both plasma and plasma-treated solution significantly decreased cell viability and proliferation of 6606PDA cancer cells, whereas mouse fibroblasts were less affected. Repeated intraperitoneal treatment of NTP-conditioned medium decreased tumor growth in vivo as determined by magnetic resonance imaging, leading to reduced tumor mass and improved median survival (61 vs 52 days; p < 0.024). Tumor nodes treated by NTP-conditioned medium demonstrated large areas of apoptosis with strongly inhibited cell proliferation. Contemporaneously, no systemic effects were found. Apoptosis was neither present in the liver nor in the gut. Also, the concentration of different cytokines in splenocytes or blood plasma as well as the distribution of various hematological parameters remained unchanged following treatment with NTP-conditioned medium. These results suggest an anticancer role of NTP-treated solutions with little to no systemic side effects being present, making NTP-treated solutions a potential complementary therapeutic option for advanced tumors.

Perspectives in General Surgery

Non-thermal plasma (NTP) offers promising opportunities to advance and refine surgical practice. The combination of stimulating tissue proliferation and decreasing bacterial load predestines NTP as add-on tool in wound treatment. Additionally, plasma-based modification of foreign materials, such as, vascular grafts or osteosynthesis materials improves their biocompatibility. Surgery in oncology is another auspicious field of application. Micrometastasis in the margins of excised tumors often cause tumor relapse. Due to selective induction of apoptosis in tumor cells, NTP treatment of wound margins after surgical bulk removal offers great potential minimize disease recurrence and improve patients’ outcome. However, compatibility with the special setting in an operating theatre is an issue not addressed yet with most plasma sources.

Cold Physical Plasma Selectively Elicits Apoptosis in Murine Pancreatic Cancer Cells In Vitro and In Ovo

Background/Aim: Poor prognosis of pancreatic cancer has remained almost unchanged in recent years. Cold physical plasma was suggested as an innovative anticancer strategy, but its selective killing activity of malignant over non-malignant cells has only partially been explored. The present study aimed at exploring the effect of cold physical plasma on cellular viability. Materials and Methods: Induction of cell death and apoptosis by cold physical plasma was investigated in murine PDA6606 pancreatic cancer cells and primary murine fibroblasts in vitro (2D and 3D cultures) and in ovo. Results: Plasma increased apoptosis in PDA6606 to a significantly higher extent compared to fibroblasts. Antioxidants abrogated these effects, suggesting a prime role of reactive oxygen species in plasma-induced apoptosis. Plasma increased apoptosis of 3D PDA6606 multicellular spheres grown in vitro and in ovo, to significantly higher rates compared to that of fibroblasts, with minimum in ovo inflammation or necrosis observed by hematoxylin and eosin staining (H&E). Conclusion: These data support the future intra-operative application of cold physical plasma for the treatment of microscopic residual tumor tissue after surgical resection.

Cold physical plasma treated buffered saline solution as effective agent against pancreatic cancer cells

BACKGROUND Cold physical plasma has been suggested as a new anticancer tool recently. However, direct use of plasma is limited to visible tumors and in some clinical situations, is not feasible. This includes repetitive treatment of peritoneal metastases, which commonly occur in advanced gastrointestinal cancer and in pancreatic cancer in particular. In case of diffuse intraperitoneal metastatic spread, Hyperthermic Intraperitoneal Intraoperative Chemotherapy (HIPEC) is used as a therapeutic approach. Plasma-treated solutions may combine non-toxic characteristics with the anticancer effects of HIPEC. Previous work has provided evidence for an anticancer efficacy of plasma-treated cell culture medium but the clinical relevance of such an approach is low due to its complex formulation and lack of medical accreditation. OBJECTIVE Plasma-treated Phosphate-Buffered Saline (PBS), which closely resembles medically certified solutions, was investigated for its cytotoxic effect on 2D monolayer murine pancreatic cancer cells in vitro. METHODS Toxicity studies of primary murine fibroblasts, PDA6606 murine pancreatic cancer cells, and COLO 357 human pancreatic cancer cells exposed to plasma-treated PBS were performed. RESULTS Plasma-treated PBS significantly decreased cancer cell metabolisms and proliferation whereas plasma-treated Dulbeccos Modified Eagle Medium had no effect. Moreover, tumor cell growth attenuation was significantly higher when compared to syngeneic primary murine fibroblasts. Both results were confirmed in a human pancreatic cancer cell line. Finally, plasma-treated PBS also decreased the size of pancreatic tumors in a three-dimensional manner, and induction of apoptosis was found to be responsible for all anticancer effects identified. CONCLUSION Plasma-treated PBS inhibited cell growth in 2D and 3D models of cancer. These results may help facilitate the development of new plasma-derived anticancer agent with clinical relevance in the future.

Kaltes Atmosphärendruckplasma im Einsatz in der Chirurgie

Kaltes Atmospharendruckplasma bietet vielfaltige Anwendungsmoglichkeiten in allen chirurgischen Fachdisziplinen. Dazu gehort u. a. die Therapie chronischer und infizierter Wunden. In der Tumorchirurgie kann kaltes Atmospharendruckplasma uber eine relativ selektive Induktion von Apoptose in Tumorzellen sowohl zur Steigerung der lokalen Radikalitat fuhren als auch in palliativen Konzepten eingesetzt werden. Weitere Moglichkeiten stellen die lokale Anwendung von kaltem Atmospharendruckplasma zur intraoperativen Blutstillung sowie zur Behandlung von Implantaten zur Verbesserung der Einheilung und als Protektion vor Infektionen dar. Dabei scheint die Anwendung nach bisherigem Kenntnisstand keine unerwunschten systemischen Wirkungen zu haben. Die Chirurgie als traditionell innovative Fachdisziplin kann in Zusammenarbeit mit Grundlagenforschern die Anwendung von kaltem Atmospharendruckplasma fur die zukunftige klinische Routineanwendung in einem breiten Anwendungsfeld vorantreiben.