Electrochemotherapy is a combination of high electric field and anticancer drugs. The treatment basis is electroporation or electropermeabilization of the cell membrane. Electroporation is a threshold phenomenon and, for efficient treatment, an adequate local distribution of electric field within the treated tissue is important. When this local electric field is not enough, there is a regrown tumor cell; however, if it is stronger than necessary, permanent damage to the tissue occurs. In the treatment of dogs, electrochemotherapy is not yet an established treatment for mast cell tumor in veterinary medicine, although there are studies showing evidence of its effectiveness. In this study, we examined electrochemotherapy of dog mast cell tumor with numerical simulation of local electric field distribution. The experimental result was used to validate the numerical models. The effect of tumor position and tissue thickness (tumor in different parts of dog body) was investigated using plate electrodes. Our results demonstrated that the electrochemotherapy is efficient and flexible, and even when the tumor extends into the subcutis, the treatment with plate electrode eliminated the tumor cells. This result suggests that electrochemotherapy is a suitable method to treat mast cell tumors in dog.
An intense electric field can be applied to increase the membrane conductance G(m) and consequently, the conductivity of cell suspension. This phenomenon is called electroporation. This mechanism is used in a wide range of medical applications, genetic engineering, and therapies. Conductivity measurements of cell suspensions were carried out during application of electric fields from 40 to 165 kV/m. Experimental results were analyzed with two electroporation models: the asymptotic electroporation model was used to estimate G(m) at the beginning and at the end of electric field pulse, and the extended Kinosita electroporation model to increase G(m) linearly in time. The maximum G(m) was 1-7 × 10(4) S/m(2), and the critical angle (when the G(m) is insignificant) was 50°-65°. In addition, the sensitivity of electroporated membrane conductance to extracellular and cytoplasmatic conductivity and cell radius has been studied. This study showed that external conductivity and cell radius are important parameters affecting the pore-opening phenomenon. However, if the cell radius is larger than 7 μm in low conductivity medium, the cell dimensions are not so important.
The combination of chemotherapy drugs and high electric field treatment in local cancer is named electrochemotherapy. The European Standard Operation Procedure of Electrochemotherapy (ESOPE) provides guidelines for treatment of cutaneous and subcutaneous tumors. The electrochemotherapy of numerous tumors varying in sizes is more convenient using needle electrodes. However, ESOPE recommends that needle electrodes are applied to deeper tumors. The application of needle electrodes to treatment of superficial small tumors seems to be practical in electrochemotherapy. Plate electrodes and gel improve the electrochemotherapy efficacy. This technique provides electric field homogeneity in irregularly shaped tissue structures (bulk tumors). We propose an investigation of needle electrode and gel in electrochemotherapy of superficial tumors. In vivo experiment with squamous cell carcinoma (SCC) spontaneous nodules in dog was used to validate the mathematical tissue model. The numerical model considers the tissue conductivity dependent on local electric field. Our studies demonstrated that conductive gel is important for effective treatment of superficial tumors with needle electrodes. The needle electrodes and gel presented reduction of medium current, increased the tumor-free margin, and improved the practical application in relation to plate electrode.
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 (ECT) is a technique that combines chemotherapy with local application of specific electric pulses with the aim of increasing the permeability of the plasma membrane in a reversible way, improving the influx of chemotherapeutic drugs into the cytoplasm and potentiating their cytotoxic effects. This technique has broadened the range of possible treatments for oncological patients, either on its own or as adjuvant to surgical procedures. It is especially useful in tumors located in regions with only a small surgical safety margin, such as the limb extremities, skull, oral cavity, neck and perianal region, among others. ECT makes it feasible to perform procedures more conservatively, or even to perform otherwise infeasible procedures, by expanding the margins without removing healthy tissues. The objective of this paper is to provide a brief bibliographic review of the principles, applications and future possibilities of electrochemotherapy, helping to disseminate pertinent information about this relatively new technique for the treatment of cancer.
Electrochemotherapy is a new modality of local cancer treatment that increases the delivery of chemotherapy drugs into tumor cells by applying intense electric fields. This novel electrochemotherapy application was applied as an adjuvant to surgery and eliminated intranasal tumors in dog. The treatment challenges are the surgery limitations due to anatomy and residual tumor in the bone cavity. Most of the tumoral mass on nasal cavity was surgically removed. The internal nasal cavity was immersed in liquid and bleomycin before applying electric field. The solution was necessary to increase the superficial contact between plate electrodes and residual tumor. The numerical study demonstrated electrochemotherapy efficiency in different clinical situations. The proximity between electrodes and bone (<3 mm) and bone irregularities affect the electric field distribution on tumoral tissue. The tumoral tissue around bone protuberances tends to be eliminated. Electrochemotherapy with plate electrodes inside the cavity might not be effective. Different values of electric conductivity solution were studied; the ideal value was 0.5 S/m. The numerical and experimental results confirm the successful application of electrochemotherapy on dog nasal cavity.
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