TY - JOUR
T1 - Preclinical validation of electrochemotherapy as an effective treatment for brain tumors
AU - Agerholm-Larsen, Birgit
AU - Iversen, Helle K
AU - Ibsen, Per
AU - Moller, Jakob M
AU - Mahmood, Faisal
AU - Jensen, Kurt Svarre
AU - Gehl, Julie
AU - Møller, Jakob Møllenbach
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Electrochemotherapy represents a strategy to enhance chemotherapeutic drug uptake by delivering electrical pulses which exceed the dielectric strength of the cell membrane, causing transient formation of structures that enhance permeabilization. Here we show that brain tumors in a rat model can be eliminated by electrochemotherapy with a novel electrode device developed for use in the brain. By using this method, the cytotoxicity of bleomycin can be augmented more than 300-fold because of increased permeabilization and more direct passage of drug to the cytosol, enabling highly efficient local tumor treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment, we found that 9 of 13 rats (69%) receiving electrochemotherapy displayed a complete elimination of tumor, in contrast to control rats treated with bleomycin only, pulses only, or untreated where tumor progression occurred in each case. Necrosis induced by electrochemotherapy was restricted to the treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool to treat primary brain tumors and brain metastases.
AB - Electrochemotherapy represents a strategy to enhance chemotherapeutic drug uptake by delivering electrical pulses which exceed the dielectric strength of the cell membrane, causing transient formation of structures that enhance permeabilization. Here we show that brain tumors in a rat model can be eliminated by electrochemotherapy with a novel electrode device developed for use in the brain. By using this method, the cytotoxicity of bleomycin can be augmented more than 300-fold because of increased permeabilization and more direct passage of drug to the cytosol, enabling highly efficient local tumor treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment, we found that 9 of 13 rats (69%) receiving electrochemotherapy displayed a complete elimination of tumor, in contrast to control rats treated with bleomycin only, pulses only, or untreated where tumor progression occurred in each case. Necrosis induced by electrochemotherapy was restricted to the treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool to treat primary brain tumors and brain metastases.
U2 - 10.1158/0008-5472.can-11-0451
DO - 10.1158/0008-5472.can-11-0451
M3 - Journal article
C2 - 21507935
SN - 0008-5472
VL - 71
SP - 3753
EP - 3762
JO - Cancer Research
JF - Cancer Research
IS - 11
ER -