Changing electrode orientation improves the efficacy of electrochemotherapy of solid tumors in mice

Electrochemotherapy is a new and promising approach in treatment of tumors employing locally applied high voltage d.c. electric pulses in combination with chemotherapeutic drugs. Increased permeability of the plasma membrane, induced by electric pUlses, enables the chemotherapeutic drugs to enter into the cytosol, thus potentiating their anti-tumor effectiveness. In most of the studies published until now, trains of pulses were delivered via percutaneous parallel plate electrodes, so that the tumor was situated in between the electrodes. In our study the train of electric pulses was divided into two trains, the second one oriented perpendicularly to the first one. This changing of the electrode orientation resulted in improved anti-tumor efficacy of the electrochemotherapy: prolonged tumor growth delay and higher percentage of short and long term complete responses of the tumors. In this paper we also suggest a possible explanation for the observed effect, based on the knowledge of electric field distribution in the tissue and induced transmembrane potential.