Antitumour effectiveness of hyperthermia is potentiated by local application of electric pulses to LPB tumours in mice.
BACKGROUND
The aim of our study was to determine whether local application of electric pulses to tumours, which induce transient reduction of tumour perfusion, could potentiate the antitumour effectiveness of hyperthermia.


METHODS
The antitumour effectiveness of local application of electric pulses (1300 V/cm, 100 micros, 1 Hz) and 910 MHz local hyperthermia at 43.5 degrees C, alone or in combination, was determined on LPB tumours in C57Bl/6 mice by measurement of tumour growth delay, changes in tumour perfusion using the Patent blue technique and extent of tumour necrosis.


RESULTS
When hyperthermia was performed immediately after application of electric pulses, at a time of maximally reduced tumour perfusion, greater than additive antitumour effectiveness was observed, resulting in 14.5 +/- 3.1 days growth delay of tumours that regrew and 43% complete responses. Single treatment, application of electric pulses or hyperthermia had minor or no effect on tumour growth. When hyperthermia was performed 24 hours after application of electric pulses, at a point when tumour perfusion was restored, the effect of both treatments was additive, resulting in 4.1 +/- 1.1 days growth delay and no cures.


CONCLUSIONS
The probable mechanisms for the observed, more than additive, interaction when hyperthermia was performed immediately after application of electric pulses are the potentiation of thermic cytotoxicity, due to the reduced tumour perfusion induced by application of electric pulses and prolonged tumour perfusion reduction after combined treatment leading to additional cell kill, due to the protracted ischemia.
Institute of Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia.
Katarina Barbara
KB
Karner
Hotimir
H
Lesnicar
Maja
M
Cemazar
Gregor
G
Sersa
D000818:Animals; D003131:Combined Modality Therapy; D018274:Electroporation / Q000379:methods*; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology / Q000628:therapy*; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion; D011897:Random Allocation; D012513:Sarcoma, Experimental / Q000473:pathology / Q000628:therapy*