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

Ausgeprägte Synergie zwischen Hyperthermie und moduliertem elektromagnetischem Feld bei der Abtötung von Tumorzellen

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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.

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Authors and Affiliations

  1. 1„Frederic Joliot Curie” National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary

    Gabor Andocs & Lajos Balogh

  2. Department of Pharmacology and Toxicology, Faculty of Veterinary Science, St. István University, Budapest, Hungary

    Gabor Andocs

  3. Clinic of Radiooncology, Klinikum Nuremberg, Nuremberg, Germany

    Helmut Renner

  4. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

    Laszlo Fonyad

  5. Department of Pathology, Faculty of Veterinary Science, St. István University, Budapest, Hungary

    Csaba Jakab

  6. Biotechnics Department, Faculty of Engineering, St. István University, Gödöllő, Hungary

    Andras Szasz

  7. Hitzlisbergstraße 24a, 6006, Luzern, Switzerland

    Helmut Renner

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  1. Gabor Andocs
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  2. Helmut Renner
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Correspondence to Helmut Renner.

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Andocs, G., Renner, H., Balogh, L. et al. Strong synergy of heat and modulated electromagnetic field in tumor cell killing. Strahlenther Onkol 185, 120–126 (2009). https://doi.org/10.1007/s00066-009-1903-1

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  • DOI: https://doi.org/10.1007/s00066-009-1903-1

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