Oral Mucosa Model for Electrochemotherapy Treatment of Dog Mouth Cancer: Ex Vivo, In Silico, and In Vivo Experiments

Abstract

Electrochemotherapy (EQT) is a local cancer treatment well established to cutaneous and subcutaneous tumors. Electric fields are applied to biological tissue in order to improve membrane permeability for cytotoxic drugs. This phenomenon is called electroporation or electropermeabilization. Studies have reported that tissue conductivity is electric field dependent. Electroporation numerical models of biological tissues are essential in treatment planning. Tumors of the mouth are very common in dogs. Inadequate EQT treatment of oral tumor may be caused by significant anatomic variations between dogs and tumor position. Numerical models of oral mucosa and tumor allow the treatment planning and optimization of electrodes for each patient. In this work, oral mucosa conductivity during electroporation was characterized by measuring applied voltage and current of ex vivo rats. This electroporation model was used with a spontaneous canine oral melanoma. The model outcomes of oral tumor EQT is applied in different parts of the oral cavity including near bones and the hard palate. The numerical modeling for treatment planning will help the development of new electrodes and increase the EQT effectiveness.

Electrochemotherapy in the treatment of neoplasms in dogs and cats

“…Techniques to avoid interferences on cardiac electrical activity are also being developed. The planning of the electric field is critical to the effectiveness of ECT and must be correlated with the site of application due to the heterogeneity of tissue conductivities, which may result in an irregular distribution of the electric field, and care must be taken not to affect adjacent organs (Domenge et al 1996, Deodhar et al 2011, Mali et al 2008, Suzuki et al 2018. Electrochemotherapy is under development.…”

“…The waveforms used in electrochemotherapy are square-wave mono-or biphasic pulses. The most common electric parameters used in electrochemotherapy are 8 pulses, 100 µs length, 1-5 kHz frequency and 1000 V/cm (for needle parallel electrodes) or 1300 V/cm (plate electrodes) of electric field intensity 1 a , Pavlin et al 2009, Tozon et al 2016, Maglietti et al 2016, Pierini et al 2016, Suzuki et al 2018, Lowe et al 2017. For this technique, bleomycin and cisplatin are the main drugs used (Sersa et al 2008, Escoffre andRols 2012).…”

Electrochemotherapy Effectiveness Loss due to Electric Field Indentation between Needle Electrodes: A Numerical Study

“…Tissue electrical conductivity, as a function of the electric field, reaches a constant value, called σ max , inasmuch as the local electric field approaches E irrev ( Figure 2 ). The postelectroporation conductivity ( σ max ) values are usually estimated through mathematical modeling with data from ex vivo or in vivo experiments [ 7 , 20 ]. In this work, the tissues were characterized by using the values from Table 1 in ( 2 )–( 4 ).…”

“…The electric field distribution in biological tissues has been studied for decades, and recent in silico experiments have taken advantage of years of bioelectrical impedance analysis [ 6 , 7 ] and powerful processors. Through in silico experiments, several different scenarios can be run, which have allowed scientists and clinicians to understand and predict problems in treatment effectiveness.…”

Electroporation as the Immunotherapy Strategy for Cancer in Veterinary Medicine: State of the Art in Latin America

“…In particular, the group of Dr. Marshall made several publications on this topic [ 10 , 70 , 97 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. The use of ECT in veterinary medicine began in 2008 in Brazil by the group of Dr. Rangel [ 109 , 110 , 111 , 112 , 113 , 114 ], closely followed by the group of Dr. Marshall, from Argentina, in 2009. Although the treatment had been used in human medicine in Europe since 2006, there were no devices available in Latin America for human nor veterinary medicine at that time.…”