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- ItemRadiofrequency Electromagnetic Fields Cause Non-Temperature-Induced Physical and Biological Effects in Cancer Cells(Basel : MDPI, 2022) Wust, Peter; Veltsista, Paraskevi D.; Oberacker, Eva; Yavvari, Prabhusrinivas; Walther, Wolfgang; Bengtsson, Olof; Sterner-Kock, Anja; Weinhart, Marie; Heyd, Florian; Grabowski, Patricia; Stintzing, Sebastian; Heinrich, Wolfgang; Stein, Ulrike; Ghadjar, PirusNon-temperature-induced effects of radiofrequency electromagnetic fields (RF) have been controversial for decades. Here, we established measurement techniques to prove their existence by investigating energy deposition in tumor cells under RF exposure and upon adding amplitude modulation (AM) (AMRF). Using a preclinical device LabEHY-200 with a novel in vitro applicator, we analyzed the power deposition and system parameters for five human colorectal cancer cell lines and measured the apoptosis rates in vitro and tumor growth inhibition in vivo in comparison to water bath heating. We showed enhanced anticancer effects of RF and AMRF in vitro and in vivo and verified the non-temperature-induced origin of the effects. Furthermore, apoptotic enhancement by AM was correlated with cell membrane stiffness. Our findings not only provide a strategy to significantly enhance non-temperature-induced anticancer cell effects in vitro and in vivo but also provide a perspective for a potentially more effective tumor therapy.
- ItemIn Vitro Examinations of Cell Death Induction and the Immune Phenotype of Cancer Cells Following Radiative-Based Hyperthermia with 915 MHz in Combination with Radiotherapy(Basel : MDPI, 2021) Hader, Michael; Streit, Simon; Rosin, Andreas; Gerdes, Thorsten; Wadepohl, Martin; Bekeschus, Sander; Fietkau, Rainer; Frey, Benjamin; Schlücker, Eberhard; Gekle, Stephan; Gaipl, Udo S.Multimodal tumor treatment settings consisting of radiotherapy and immunomodulating agents such as immune checkpoint inhibitors are more and more commonly applied in clinics. In this context, the immune phenotype of tumor cells has a major influence on the anti-tumor immune response as well as the composition of the tumor microenvironment. A promising approach to further boost anti-tumor immune responses is to add hyperthermia (HT), i.e., heating the tumor tissue between 39 °C to 45 °C for 60 min. One key technique is the use of radiative hyperthermia systems. However, knowledge is limited as to how the frequency of the used radiative systems affects the immune phenotype of the treated tumor cells. By using our self-designed in vitro hyperthermia system, we compared cell death induction and expression of immune checkpoint molecules (ICM) on the tumor cell surface of murine B16 melanoma and human MDA-MB-231 and MCF-7 breast cancer cells following HT treatment with clinically relevant microwaves at 915 MHz or 2.45 GHz alone, radiotherapy (RT; 2 × 5 Gy or 5 × 2 Gy) alone or in combination (RHT). At 44 °C, HT alone was the dominant cell death inductor with inactivation rates of around 70% for B16, 45% for MDA-MB-231 and 35% for MCF-7 at 915 MHz and 80%, 60% and 50% at 2.45 GHz, respectively. Additional RT resulted in 5-15% higher levels of dead cells. The expression of ICM on tumor cells showed time-, treatment-, cell line- and frequency-dependent effects and was highest for RHT. Computer simulations of an exemplary spherical cell revealed frequency-dependent local energy absorption. The frequency of hyperthermia systems is a newly identified parameter that could also affect the immune phenotype of tumor cells and consequently the immunogenicity of tumors.