Andras Szasz

Strong synergy of heat and modulated electromagnetic field in tumor cell killing

Background and Purpose:Hyperthermia is an emerging complementary method in radiooncology. Despite many positive studies and comprehensive reviews, the method is not widely accepted as a combination to radiotherapy. Modulated electrohyperthermia (mEHT; capacitive, electric field modulated, 13.56 MHz) has been used in clinical practice for almost 2 decades in Germany, Austria and Hungary. This in vivo study in nude mice xenograft tumors compares mEHT with “classic” radiative hyperthermia (radHT).Material and Methods:Nude mice were xenografted with HT29 human colorectal carcinoma cells. 28 mice in four groups with seven animals each and two tumors per animal (totally 56 tumors) were included in the present study: group 1 as untreated control; group 2 treated with radHT at 42 °C; group 3 treated with mEHT at identical 42 °C; group 4 treated with mEHT at 38 °C (by intensively cooling down the tumor). 24 h after treatment, animals were sacrificed and the tumor cross sections studied by precise morphological methods for the respective relative amount of “dead” tumor cells.Results:The effect of mEHT established a double effect as a synergy between the purely thermal (temperature-dependent) and nonthermal (not directly temperature-dependent) effects. The solely thermal enhancement ratio (TER) of cell killing was shown to be 2.9. The field enhancement ratio (FER) at a constant temperature of 42 °C was measured as 3.2. Their complex application significantly increased the therapeutic enhancement to 9.4.Conclusion:mEHT had a remarkable cancer cell-killing effect in a nude mice xenograft model.Hintergrund und Ziel:Die Hyperthermie ist eine aufstrebende ergänzende Therapie in der Radioonkologie. Trotz zahlreicher positiver Studien und umfassender Reviews ist diese Methode immer noch nicht als Kombination zur Radiotherapie anerkannt. Die modulierte Elektrohyperthermie (mEHT; kapazitiv mit moduliertem elektrischem Feld, 13,56 MHz) wird seit fast 2 Jahrzehnten in Deutschland, Österreich und Ungarn klinisch angewandt. Die vorliegende In-vivo-Studie vergleicht in einem Xenograft-Nacktmaus-Tumormodell die mEHT mit der „klassischen“ radiativen Hyperthermie (radHT).Material und Methodik:Nacktmäuse wurden mit humanen kolorektalen HT29-Tumorzellen xenotransplantiert. 28 Mäuse in vier Gruppen zu je sieben Tieren mit zwei Tumoren pro Tier (gesamt 56 Tumoren) wurden in diese Studie einbezogen: Gruppe 1 als unbehandelte Kontrollgruppe; Gruppe 2 behandelt mit radHT bei 42 °C; Gruppe 3 behandelt mit mEHT ebenfalls bei 42 °C; Gruppe 4 behandelt mit mEHT bei 38 °C (durch intensive Kühlung des Tumors). 24 h nach der Behandlung wurden die Tiere getötet und die Tumorquerschnitte morphologisch auf den jeweiligen Anteil „toter“ Tumorzellen untersucht.Ergebnisse:Die Behandlung mit mEHT zeigte eine doppelte Wirkung als Synergie zwischen dem ausschließlich thermalen (temperaturabhängigen) und dem nichtthermalen (nicht direkt temperaturabhängigen) Effekt. Folgende Faktoren wurden gemessen: die durch alleinige Hyperthermie bedingte Verstärkung der Zellzerstörung („thermal enhancement ratio“ [TER]) mit dem Faktor 2,9; der alleinige Feldverstärkungseffekt („field enhancement ratio“ [FER]) bei konstanter Temperatur von 42 °C mit dem Faktor 3,2; die Kombination beider Effekte mit einem signifikant erhöhten Faktor von 9,4.Schlussfolgerung:Die durch ein moduliertes elektrisches Feld (13,56 MHz) erzeugte mEHT hatte in einem Nacktmaus-Xenograft-Tumormodell einen ausgeprägten tumorzellabtötenden Effekt.

Oncothermia treatment of cancer: from the laboratory to clinic.

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.

An Energy Analysis of Extracellular Hyperthermia

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, thecell 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.

Hyperthermia today: Electric energy, a new opportunity in cancer treatment

Hyperthermia is an ancient, but nowadays rapidly developing treatment method in tumor-therapy. Its new paradigm applied in the electro-hyperthermia (oncothermia), which provides energy by means of electric-field and produces non-equilibrium thermal situation in the tissue. The temperature gradients formed in stationary conditions, destroy the membrane of the malignant cells and selectively eliminate the cancer tissue. The characteristic control parameter is the absorbed energy-dose, which is partly used to make the distortions, partly to increase the temperature of the target. This type of technique could be applied for some tumor sites, including brain, soft tissues, liver and abdominal masses, pancreatic cancer, head and neck tumors as well.

Nitriding of stainless steel in an rf plasma

Treatment of stainless steels in an rf‐powered nitrogen plasma achieves a much increased rate of nitriding, as well as higher hardness and corrosion resistance than traditional nitriding. Small amounts of adsorbed hydrogen are found to be necessary initially, and the process of nitriding is modeled on the basis of this hydrogen increasing the surface sticking coefficient for nitrogen, which is followed by nitrogen diffusion into bulk in the form of nitrogen‐vacancy (weakly bound) pairs. The detailed microstructural role of chromium in the process is also discussed.

Hyperthermia versus Oncothermia: Cellular Effects in Complementary Cancer Therapy

Hyperthermia means overheating of the living object completely or partly. Hyperthermia, the procedure of raising the temperature of a part of or the whole body above normal for a defined period of time, is applied alone or as an adjunctive with various established cancer treatment modalities such as radiotherapy and chemotherapy. However, hyperthermia is not generally accepted as conventional therapy. The problem is its controversial performance. The controversy is originated from the complications of the deep heating and the focusing of the heat effect. The idea of oncothermia solves the selective deep action on nearly cellular resolution. We would like to demonstrate the force and perspectives of oncothermia, as a highly specialized hyperthermia in clinical oncology. Our aim is to prove the ability of oncothermia to be a candidate to become a widely accepted modality of the standard cancer care. We would like to show the proofs and the challenges of the hyperthermia and oncothermia applications to provide the presently available data and summarize the knowledge in the topic. Like many early stage therapies, oncothermia lacks adequate treatment experience and long-range, comprehensive statistics that can help us optimize its use for all indications.

Dose concept of oncological hyperthermia: Heat-equation considering the cell destruction

We shall assume, of course, that the objective of hyperthermia is to destroy the malignant cells. Destruction definitely needs energy. Description and quality assurance of hyperthermia use the Pennes heat equation to describe the processes. However the energy balance of the Pennes-equation does not contain the hyperthermic cell-destruction energy, which is a mandatory factor of the process. We propose a generalization of the Pennes-equation, inducing the entire energy balance. The new paradigm could be a theoretical basis of the till now empirical dose-construction for oncological hyperthermia. The cell destruction is a non-equilibrium thermodynamical process, described by the equations of chemical reactions. The dynamic behavior (time dependence) has to be considered in this approach. We are going to define also a dose concept that can be objectively compared with other oncological methods. We show how such empirical dose as CEM43oC could be based theoretically as well.

Physical Background and Technical Realizations of Hyperthermia

Hyperthermia is a medical heat-treatment, widely used in various medical fields and has a well-recognized effect in oncology. It is an ancient treatment. However, when making hyperthermia we are limited by numerous biological, physical/technical and physiological problems. The word hyperthermia means increased temperature by heating of tumors. This relatively simple, physical-physiological method has a phoenix-like history with some bright successes and many deep disappointments. Why is this enigma? What do we have in hand? Answers lie in the applied techniques.

Chemical mechanisms in electroless deposition. A study on the role of hydrogen in layer formation

Abstract Mechanisms of formation of electroless NiP amorphous alloys have been studied with special emphasis on the role of hydrogen. It is proposed that hydrogen atoms produced during layer nucleation and growth are occlded by the deposit during the process of formation and that they have an important role in stabilizing the amorphous structure. The hydrogen may also play a part in the whole autocatalytic process. The hydrogen evolution is accompanied by incorporation of phosphorus, which to some extent takes over the role of the metalloid necessary to stabilize the amorphous structure. Airation of the electroless bath is found to decrease hydrogen liberation and to make the layers more uniform, but causes their thermal stability to decrease. Possible explanations for these effects are discussed.

Metal-Framed Spectacles and Implants and Specific Absorption Rate Among Adults and Children Using Mobile Phones at 900/1800/2100 MHz

The specific absorption rate (SAR) from mobile telephones at horizontal and vertical positions is investigated in human adult and child heads wearing metal-rim spectacles and having metallic implants. The SAR values calculated by Finite Difference Time Domain (FTDT) method are compared to the actual ANSI/IEEE standards and to the 900/1800/2100 MHz electromagnetic radiation limits according to EU standards. Our calculation shows a maximum of the cellular SAR in the child head, which in the case of metallic implant could be as much as 100% higher than in the adult head. The averaging on 1 and 10 g tissue-masses shows SAR generally under the limit of 519/1999/EC standards. However, in the case of 2100 MHz with vertical position of the phone for adults and of the 900 MHz for children with metallic implants the ANSI/IEEE limits are exceeded.