TY - JOUR
T1 - Definition of novel electrochemotherapy parameters and validation of their in vitro and in vivo effectiveness
AU - Spugnini, Enrico P.
AU - Melillo, Alessandro
AU - Quagliuolo, Lucio
AU - Boccellino, Mariarosaria
AU - Vincenzi, Bruno
AU - Pasquali, Paola
AU - Baldi, Alfonso
PY - 2014
Y1 - 2014
N2 - Electrochemotherapy (ECT) is a cancer therapy that conjugates the administration of a chemotherapy agent to the delivery of permeabilizing pulses released singularly or as bursts. This approach results in higher number of anticancer molecules delivered to their biological targets, but is also associated to undesirable side effects such as pain and muscular contractions. A new electroporator delivering train of eight biphasic pulses at the voltage of 1,300V/cm lasting 50+50μsec each, with a frequency of 1Hz, and with 10-μsec interpulse intervals (total treatment time: 870μsec/cm2 of treated area) was tested in vitro on the human lung cancer cell line A549 and in vivo, both in mice xenografts and privately owned rabbits with spontaneous tumors. The tumor cell line was treated with electroporation using the new parameters, that showed improved drug efficacy in causing cell death. Mice with chemoresistant xenografts were treated as well with either the new parameters and with a previous protocol, confirming the higher tolerability and efficacy of the novel parameters. Finally, a cohort of six pet rabbits with advanced skin neoplasms were enrolled in a compassionate trial using the new parameters in adjuvant fashion. In terms of efficacy, none of the rabbits experienced tumor recurrence, showing minimal discomfort during the ECT sessions. The data described, demonstrate that the new permeabilizing protocol adopting biphasic electric pulses displays a significant higher efficacy compared to previous ECT treatments and substantial reduction of the associated morbidity.
AB - Electrochemotherapy (ECT) is a cancer therapy that conjugates the administration of a chemotherapy agent to the delivery of permeabilizing pulses released singularly or as bursts. This approach results in higher number of anticancer molecules delivered to their biological targets, but is also associated to undesirable side effects such as pain and muscular contractions. A new electroporator delivering train of eight biphasic pulses at the voltage of 1,300V/cm lasting 50+50μsec each, with a frequency of 1Hz, and with 10-μsec interpulse intervals (total treatment time: 870μsec/cm2 of treated area) was tested in vitro on the human lung cancer cell line A549 and in vivo, both in mice xenografts and privately owned rabbits with spontaneous tumors. The tumor cell line was treated with electroporation using the new parameters, that showed improved drug efficacy in causing cell death. Mice with chemoresistant xenografts were treated as well with either the new parameters and with a previous protocol, confirming the higher tolerability and efficacy of the novel parameters. Finally, a cohort of six pet rabbits with advanced skin neoplasms were enrolled in a compassionate trial using the new parameters in adjuvant fashion. In terms of efficacy, none of the rabbits experienced tumor recurrence, showing minimal discomfort during the ECT sessions. The data described, demonstrate that the new permeabilizing protocol adopting biphasic electric pulses displays a significant higher efficacy compared to previous ECT treatments and substantial reduction of the associated morbidity.
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U2 - 10.1002/jcp.24548
DO - 10.1002/jcp.24548
M3 - Article
C2 - 24403005
AN - SCOPUS:84901236115
VL - 229
SP - 1177
EP - 1181
JO - Journal of cellular and comparative physiology
JF - Journal of cellular and comparative physiology
SN - 0021-9541
IS - 9
ER -