Reversible electropermeabilization (RE) is an ultrastructural phenomenon that transiently increases the permeability of the cell membrane upon application of electrical pulses. The technique was described in 1972 by Neumann and Rosenheck and is currently used in a variety of applications, from medicine to food processing. In oncology, RE is applied for the intracellular transport of chemotherapeutic drugs as well as the delivery of genetic material in gene therapies and vaccinations. This review summarizes the physical changes of the membrane, the particularities of bleomycin, and the immunological aspects involved in electrochemotherapy and gene electrotransfer, two important EP-based cancer therapies in human and veterinary oncology.
Recent preclinical and clinical studies have used viral vectors in gene therapy research, especially nonreplicating adenovirus encoding strategic therapeutic genes for cancer treatment. Adenoviruses were the first DNA viruses to go into therapeutic development, mainly due to well-known biological features: stability in vivo, ease of manufacture, and efficient gene delivery to dividing and nondividing cells. However, there are some limitations for gene therapy using adenoviral vectors, such as nonspecific transduction of normal cells and liver sequestration and neutralization by antibodies, especially when administered systemically. On the other hand, adenoviral vectors are amenable to strategies for the modification of their biological structures, including genetic manipulation of viral proteins, pseudotyping, and conjugation with polymers or biological membranes. Such modifications provide greater specificity to the target cell and better safety in systemic administration; thus, a reduction of antiviral host responses would favor the use of adenoviral vectors in cancer immunotherapy. In this review, we describe the structural and molecular features of nonreplicating adenoviral vectors, the current limitations to their use, and strategies to modify adenoviral tropism, highlighting the approaches that may allow for the systemic administration of gene therapy.
1 May 2019 in Austral journal of veterinary sciences
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.
Melanocytoma and malignant melanoma are the most typical eye tumors in dogs and cats. Due to the presence of melanin, the general appearance is often highly pigmented in a nodular formation with well-defined borders. Electrochemotherapy (ECT) is a therapy combining reversible electroporation and anti-neoplastic drugs to enhance their cytotoxic effects through increasing cellular uptake by the electroporated tumor cells. In this article, the use of adjuvant ECT for the treatment of canine ocular melanoma is reported. The presurgical exams (blood count, renal and liver functions, echocardiogram, and electrocardiogram) were within the normal range, as were the chest radiography and abdominal ultrasound without signs of metastases. On the day of the surgery, an excisional biopsy of the tumor was performed without safety margins by keratectomy associated with conjunctivectomy and adjuvant ECT in the surgical site and peri-tumoral region. The animal was followed for approximately 7 months and remained without evidence of tumor recurrence. A complete resolution of corneal opacification was also observed. To our knowledge, this is the first report of the use of ECT in an ocular neoplasm. From a comparative oncology perspective, this report opens the way for future therapeutic approaches in superficial ocular cancers in veterinary and human medicine.(c) 2023 Urmia University. All rights reserved.
O presente relato visa descrever os achados macroscópicos e histopatológicos de um canino com mielolipoma em glândula adrenal esquerda. Tumores de glândula adrenal são neoplasias frequentes em cães, porém mielolipomas são geralmente encontrados em bovinos ou primatas sendo infrequente em outras espécies. Um cadáver de um canino, sem raça definida, com diagnóstico clínico de doença renal aguda foi encaminhado ao Laboratório de Patologia para a realização da necropsia. Na abertura da cavidade abdominal foi encontrada uma massa crânio-medial ao rim esquerdo que circundava o hilo renal. O rim esquerdo apresentava leve aumento de volume. A massa foi diagnosticada microscopicamente como Mielolipoma e no rim esquerdo foram encontradas alterações que sugeriam isquemia renal. O diagnóstico de mielolipoma de adrenal foi considerado um achado incidental de necropsia, sendo a causa da morte deste canino uma doença renal bilateral de origem não determinada. Porém, apesar deste tumor não estar relacionado ao óbito do animal lesões compatíveis com isquemia no rim esquerdo foram encontradas, demonstrando, que tumores benignos de adrenal, como o mielolipoma, podem gerar lesões por compressão no rim.
O presente relato visa descrever os achados macroscópicos e histopatológicos de um canino com mielolipoma em glândula adrenal esquerda. Tumores de glândula adrenal são neoplasias frequentes em cães, porém mielolipomas são geralmente encontrados em bovinos ou primatas sendo infrequente em outras espécies. Um cadáver de um canino, sem raça definida, com diagnóstico clínico de doença renal aguda foi encaminhado ao Laboratório de Patologia para a realização da necropsia. Na abertura da cavidade abdominal foi encontrada uma massa crânio-medial ao rim esquerdo que circundava o hilo renal. O rim esquerdo apresentava leve aumento de volume. A massa foi diagnosticada microscopicamente como Mielolipoma e no rim esquerdo foram encontradas alterações que sugeriam isquemia renal. O diagnóstico de mielolipoma de adrenal foi considerado um achado incidental de necropsia, sendo a causa da morte deste canino uma doença renal bilateral de origem não determinada. Porém, apesar deste tumor não estar relacionado ao óbito do animal lesões compatíveis com isquemia no rim esquerdo foram encontradas, demonstrando, que tumores benignos de adrenal, como o mielolipoma, podem gerar lesões por compressão no rim.