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Oncothermia is a long-time applied method (since 1989) in oncology. Its clinical results excellently show its advantages, however the details of its mechanism are under investigation even today. The method is based on a self-selective process of energy concentration and targets the membrane of the malignant cell, using the temperature gradient and the beta-dispersion of the membrane proteins. To prove the theory we show the experimental evidences in vitro experiments where we showed the definite difference between the conventional heating and the oncothermia at the same temperature. In the next step, we studied some xenograft nude-mice models, verifying the temperature-dependent and non temperature dependent factors. In addition, the synergic effect with some chemotherapies were studied, having more efficacy of the oncothermia with drugs than the conventional heating. These experiments show the definite advantages of the oncothermia compared to its classical counterpart, acting on the same temperature. We have also proved the beneficial effect of oncothermia treatment in the veterinary practice Oncothermia is applied in numerous clinics and hospitals, and we would like to show some characteristic case-reports and also the clinical benefit on the survival time elongation of liver-, pancreas-, brain-, and lung-tumor-lesions.

The classical hyperthermia effect is based on well-focused energy absorption targeting the malignant tissue. The treatment temperature has been considered as the main technical parameter. There are discussions about the mechanism and control of the process because of some doubts about the micro-mechanisms. The main idea of the extracellular hyperthermia is to heat up the targeted tissue by means of electric field, keeping the energy absorption in the extracellular liquid. This produces a temperature gradient and connected heat flow through the cell membrane, which initializes numerous nonequilibrium thermal microprocesses to destroy the cell membrane. Furthermore, before the heat shock activates the intracellular heat shock protein (HSP) mechanisms, the cell membrane has been already compromised, therefore the HSP synthesis in the cells starts secondarily only after the membrane damage. The process could explain why the nonuniform and basically unsatisfactorily high temperature locoregional hyperthermia could be effective.

Aim: Heating by nanoparticles, which are located in the tissue to be treated, is a well-recognized method in hyperthermic oncology. Our objective is to investigate selective, nanoscopic heating without concentrating extra artificial nanoparticles. We have in silico calculation to study the heating of the transmembrane protein clusters (rafts) on cell-membrane. The transmembrane protein domains have significantly higher dielectric constant than their lipid neighborhood in the membrane. This difference causes a local gradient in the Specific Absorption Rate (SAR), which could be a factor of heating of the membranes locally, as well as exciting the receptors for various signal transduction in the cells. We suppose that this process determines the observed cellular effects of modulated electro-hyperthermia (mEHT, trade-name: oncothermia). Materials and Methods: In silico models with highly specialized software (Computer Simulation Technology (CST), Darmstadt, Germany) were performed visualizing the selectivity for the membrane domains. Local raft models were created to simulate the electromagnetic (EM) effect of a 13.56 MHz excitation between two perfect electrical conductor plates, simulating the equipotential conditions of the sides of the membrane in the vicinity of the raft. The simulations were performed with near-field (EQS) solver of CST. The electric field, current density, and electric loss density were monitored by the simulations. The applied material properties and parameters refer to the recent literature. Results: In silico models show ten times higher energy-absorption of the transmembrane domains than that of its lipid-membrane surrounding, and intra-and extracellular neighborhood. Depending on the size, orientation, and location of the membrane rafts, the value of SAR varies, but we use only two simplified models to see the absorption properties. Taking into account the characteristics of the EM field effects we showed that the selective energy-absorption increased further by the cell-cell interactions. The The heated protein-clusters (membrane rafts) are used the same way as the artificial nanoparticles, while these absorbers are natural parts of the biological system.

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