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Conductive Gas Plasma Treatment Augments Tumor Toxicity of Ringer’s Lactate Solutions in a Model of Peritoneal Carcinomatosis
Reactive species generated by medical gas plasma technology can be enriched in liquids for use in oncology targeting disseminated malignancies, such as metastatic colorectal cancer. Notwithstanding, reactive species quantities depend on the treatment mode, and we recently showed gas plasma exposure in conductive modes to be superior for cancer tissue treatment. However, evidence is lacking that such a conductive mode also equips gas plasma-treated liquids to confer augmented intraperitoneal anticancer activity. To this end, employing atmospheric pressure argon plasma jet kINPen-treated Ringer’s lactate (oxRilac) in a CT26-model of colorectal peritoneal carcinomatosis, we tested repeated intraabdominal injection of such remotely or conductively oxidized liquid for antitumor control and immunomodulation. Enhanced reactive species formation in conductive mode correlated with reduced tumor burden in vivo, emphasizing the advantage of conduction over the free mode for plasma-conditioned liquids. Interestingly, the infiltration of lymphocytes into the tumors was equally enhanced by both treatments. However, significantly lower levels of interleukin (IL)4 and IL13 and increased levels of IL2 argue for a shift in intratumoral T-helper cell subpopulations correlating with disease control. In conclusion, our data argue for using conductively over remotely prepared plasma-treated liquids for anticancer treatment.
Antioxidant Defense in Primary Murine Lung Cells following Short- and Long-Term Exposure to Plastic Particles
Polystyrene nano- and micro-sized plastic particles (NMP) are one of the common plastic materials produced that dramatically pollute the environment, water, and oceanic habitats worldwide. NMP are continuously absorbed by the body through a number of routes, especially via intestinal ingestion, dermal uptake, and inhalation into the lung. Several studies provided evidence of NMP provoking oxidative stress and affecting cellular responses. Yet, the NMP effects on primary lung cells have not been studied. To this end, we isolated and cultured murine lung cells and exposed them short-term or long-term to polystyrene 0.2–6.0 µm-sized NMP. We studied cellular consequences regarding oxidative stress, morphology, and secretion profiling. Visualization, distribution, and expression analyses confirmed lung cells accumulating NMP and showed several significant correlations with particle size. Moreover, we found substantial evidence of biological consequences of small-scale NMP uptake in lung cells. Besides alterations of cytokine secretion profiles resulting in inflammatory responses, indicators of oxidative stress were identified that were accompanied by Nrf2 and β-catenin signaling changes. Our results serve as an important basis to point out the potential hazards of plastic contaminations and uptake in lung cells.
Gas plasma-treated prostate cancer cells augment myeloid cell activity and cytotoxicity
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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.