Synergetic Effect of Tumor Treating Fields and Zinc Oxide Nanoparticles on Cell Apoptosis and Genotoxicity of Three Different Human Cancer Cell Lines.

Cancer remains a leading cause of death worldwide, despite extraordinary progress. So, new cancer treatment modalities are needed. Tumor-treating fields (TTFs) use low-intensity, intermediate-frequency alternating electric fields with reported cancer anti-mitotic properties. Moreover, nanomedicine is a promising therapy option for cancer. Numerous cancer types have been treated with nanoparticles, but zinc oxide nanoparticles (ZnO NPs) exhibit biocompatibility. Here, we investigate the activity of TTFs, a sub-lethal dose of ZnO NPs, and their combination on hepatocellular carcinoma (HepG2), the colorectal cancer cell line (HT-29), and breast cancer cell lines (MCF-7). The lethal effect of different ZnO NPs concentrations was assessed by sulforhodamine B sodium salt assay (SRB). The cell death percent was determined by flow cytometer, the genotoxicity was evaluated by comet assay, and the total antioxidant capacity was chemically measured. Our results show that TTFs alone cause cell death of 14, 8, and 17% of HepG2, HT-29, and MCF-7, respectively; 10 µg/mL ZnO NPs was the sub-lethal dose according to SRB results. The combination between TTFs and sub-lethal ZnO NPs increased the cell death to 29, 20, and 33% for HepG2, HT-29, and MCF-7, respectively, without reactive oxygen species increase. Increasing NPs potency using TTFs can be a novel technique in many biomedical applications.

Low electric field parameters required to induce death of cancer cells.

Irreversible electroporation (IRE) is a novel technique that deals with killing undesirable cells, mainly cancer cells, directly without using any cytotoxic drugs. Commonly in this technique very high electric field up to 1000 V/cm is used but for very short exposure time (nanoseconds). Low electric fields (LEFs) are used before to internalize molecules and drugs inside the cells (electroendocytosis) but mainly not in killing the cells. The aim of this work is to determine the ability of using LEFs to kill cancer cells (Hela cells). The Physics idea is in making LEFs energy equivalent to IRE energy. Four IRE protocols were selected to represent very high, high, moderate and mild voltages IRE, then we make equivalent energy for each of these protocols using different LEFs' parameters of different amplitudes (7, 10, 14 and 20 V), different pulse numbers (40, 80, 160 and 320 pulses), different frequencies from 0.5 to 106.86 Hz and different pulse widths from 9.38 to 2000 ms. Each of the calculated LEF equivalent to IRE was applied on Hela cell line. The results show complete destruction of the cancer cells for all the tested exposure protocols. This damage was not due to thermal effect because the measured temperature was not changed before and after the exposure. The possible effect mechanism is discussed. It was concluded that the lethal effect on the cancer cells can be achieved using LEFs if the same energy equivalent to IRE is used. This work will help in using low-risk drug-free techniques in cancer treatment.

Revealing detrimental effects of various DC electrical energy conditions on different multidrug resistant bacteria: a comprehensive study.

The arbitrary discharge of contaminated wastes, especially that encompass multidrug resistant microbes (MDR), would broaden the circle of epidemic diseases such as COVID-19, which in turn deteriorate definitely the whole socioeconomics. Therefore, the employment of electrical stimulation techniques such as direct current (DC) with low energy considers being effective tool to impede spontaneous changes in microbial genetic makeup, which increases the prevalence of MDR phenomenon. Herein, the influence of different electric energies generated by DC electric field, volts and time on MDR-bacteria that are categorized among the highly ranked nosocomial pathogens, was scrutinized. Wherein, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Enterococcus faecalis were examined as paradigms of Gram-negative and Gram-positive pathogens. The results declared the significant superior antagonizing potency of electric energy in a dose-dependent modality rather than the applied volts or exposure time. Notably, the exposure of bacterial cultures to140 J inhibited the bacterial count by > 78% and the range of 47-73% for Gram-negative and Gram-positive, respectively. While the suppression in their metabolic activity assessed by > 75% and 41-68%, respectively; reflecting the capability of electrical energy to induce viable but non-culturable (VBNC) state. Similarly, the results of total protein, extracellular protein content and lactate dehydrogenase activity emphasized the cell wall deterioration and losing of cell membrane integrity. Additionally, the elevating in ROS upon DC-exposure participated in DNA fragmentation and plasmid decomposability by the range of 33-60%. Further, SEM micrographs depicted drastic morphological deformations after electrical treatment. Strikingly, DC-treatment impaired antibiotic resistance of the examined strains against several antibiotics by > 64.2%. Generally, our comparative detailed study revealed deleterious potentiality of different DC-protocols in defeating microbial pollution, which could be invested as efficient disinfectant alternative in various sectors such as milk sterilization and wastewater purification.

Mathematical and deep learning analysis based on tissue dielectric properties at low frequencies predict outcome in human breast cancer.

BACKGROUND: The early detection of human breast cancer represents a great chance of survival. Malignant tissues have more water content and higher electrolytes concentration while they have lower fat content than the normal. These cancer biochemical characters provide malignant tissue with high electric permittivity (ε´) and conductivity (σ). OBJECTIVE: To examine if the dielectric behavior of normal and malignant tissues at low frequencies (α dispersion) will lead to the threshold (separating) line between them and find the threshold values of capacitance and resistance. These data are used as input for deep learning neural networks, and the outcomes are normal or malignant. METHODS: ε´ and σ in the range of 50 Hz to 100 KHz for 15 human malignant tissues and their corresponding normal ones have been measured. The separating line equation between the two classes is found by mathematical calculations and verified via support vector machine (SVM). Normal range and the threshold value of both normal capacitance and resistance are calculated. RESULTS: Deep learning analysis has an accuracy of 91.7%, 85.7% sensitivity, and 100% specificity for instant and automatic prediction of the type of breast tissue, either normal or malignant. CONCLUSIONS: These data can be used in both cancer diagnosis and prognosis follow-up.

Effect of different low electric field conditions on the dielectric properties of Ehrlich tumor.

Studies of low electric fields (LEFs) effects on the permeability of the cell membrane are of great interest in molecular medicine. Electroendocytosis is a novel technique depends on using LEFs to incorporate macromolecules as anticancer drugs or genes into the cells. There are wide debates about the optimum electric conditions for electroendocytosis. In this article, Ehrlich tumor tissues were exposed to different LEFs voltages and frequencies in vitro. Dielectric properties before and after the exposure were determined. The results indicated that the exposed groups have significant high permittivity and conductivity compared to unexposed group, as well as having significant low impedance. The results indicated that dielectric measurements can be used to indicate the efficiency of electroendocytosis that as permittivity and conductivity of cell membranes increase, more molecules can passed into the cells. It was also indicated that, as the pulse amplitude increases, the LEFs influence increases, while changing pulse frequency has no obvious effect on dielectric properties of Ehrlich tumor.

Effects of aspirin on rheological properties of erythrocytes in vitro.

Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. Most studies on the mechanism of action of aspirin have concentrated on the effect of aspirin on platelets. In the present study we have tried to prove that there is another biophysical mechanism of aspirin, and that is through the effect of aspirin on erythrocytes. In this study ten blood samples were incubated with aspirin at different concentrations. The fractal dimension of erythrocytes subjected to shear rates from 5 s(-1) to 30 s(-1), in a cone and plate device designed and constructed in our lab, was calculated by processing the images of the erythrocyte. At each shear rate, the fractal dimensions of the erythrocytes were found to be strongly correlated with aspirin concentration. It is suggested that further studies using different biophysical methods must be carried out to detect the other mechanisms underlying the effect of aspirin on different blood cells.

Comparative study on the efficiency of using pulsed and direct current electrochemotherapy in treating ehrlich tumor.

The Electrochemotherapy (ECT) is an effective treatment of cutaneous and subcutaneous solid tumors. Electric field is applied to tumor nodules to enhance the delivery/distribution of a non-permeable or poorly permeable chemotherapeutic agent into the tumor cells thereby increasing local concentration of anticancer drugs. The aim of this study was to evaluate the effectiveness of using two types of electric fields in ECT, pulsed sine waves and direct current (DC) application in addition to intra-tumoral injection of bleomycin (BLM), a cytotoxic drug for treating Ehrlich tumor. The electric fields were delivered through six stainless steel needle electrodes inserted into the tumor. Tumor volume, tumor mass, percentage of fragmented DNA in the tumor tissue, relative spleen mass/total body mass, mortality rate, histological and ultrastructural examinations were investigated in each group. There were 40% complete response (CR) and 60% partial response (PR) in the group treated with DC as the electric field source of ECT, while 0% (CR) and only 25% (PR) were found in the group treated with pulsed sine wave ECT. We concluded that the utilization of low dose DC for ECT gives better results than the low voltage pulsed sine waves in treating Ehrlich tumor which may be due to the dual effects of electrochemical reactions evoked by DC application and the anti-cancer activity of BLM.