Effects of electrochemotherapy with cisplatin and peritumoral IL-12 gene electrotransfer on canine mast cell tumors: A histopathologic and immunohistochemical study

The study was aimed to characterize tumor response after combined treatment employing electrochemotherapy with IL-12 gene electrotransfer in dogs with spontaneous mast cell tumors (MCT). Eleven dogs with eleven MCTs were included in the study. Histological changes were investigated in biopsy specimens collected before the treatment (T0), and 4 (T1) and 8 weeks (T2) later. Cellular infiltrates were characterized immunohistochemically by using anti CD3, CD20, Foxp3 (Treg), CD68 and anti MHC-class II antibodies. Proliferation and anti-apoptotic activity of neoplastic cells were assessed using anti Ki-67 and Bcl-2 antibodies. Angiogenetic processes were investigated immunohistochemically by using anti Factor VIII and anti CD31 antibodies and micro vessel density quantification. Histopathological examination of samples at T0 confirmed the diagnosis and the presence of scanty infiltrates consisted mainly of T-lymphocytes and macrophages. At T1 and T2 neoplastic cells were drastically reduced in 7/11 cases, small clusters of neoplastic cells were detected in 3/11 cases and 1/11 cases neoplastic cells were still evident. Proliferation activity of neoplastic cells was significantly reduced at T1 and T2 and expression of anti-apoptotic protein at T1. Microvessel density was drastically reduced in all samples after treatment. The number of T-lymphocytes increased at T1, although not significant, while Treg were significant higher at T1 and macrophages at T2. The combined electrochemotherapy and IL-12 gene electrotransfer effectively induced a cellular response against neoplastic cells characterized mainly by the recruitment of T-lymphocytes and macrophages and a fibrotic proliferation with reduction of microvessels

Efficacy and safety of electrochemotherapy combined with peritumoral IL-12 gene electrotransfer of canine mast cell tumours

Electrochemotherapy combined with peritumoral interleukin-12 (IL-12) gene electrotransfer was used for treatment of mast cell tumours in 18 client-owned dogs. Local tumour control, recurrence rate, as well as safety of combined therapy were evaluated. One month after the therapy, no side effects were recorded and good local tumour control was observed with high complete responses rate which even increased during the observation period to 72%. IL-12 gene electrotransfer resulted in 78% of patients with detectable serum IFN- and/or IL-12 levels. In the treated tumours vascular changes as well as minimal T-lymphocytes infiltration was observed. After 1week, the plasmid DNA was not detected intra- or peritumorally and no horizontal gene transfer was observed. In summary, our study demonstrates high antitumour efficacy of electrochemotherapy combined with IL-12 electrotransfer, which also prevented recurrences or distant metastases, as well as its safety and feasibility in treatment of canine mast cell tumours

Adjuvant electrochemotherapy in veterinary patients: a model for the planning of future therapies in humans

The treatment of soft tissue tumors needs the coordinated adoption of surgery with radiation therapy and eventually, chemotherapy. The radiation therapy (delivered with a linear accelerator) can be preoperative, intraoperative, or postoperative. In selected patients adjuvant brachytherapy can be adopted. The goal of these associations is to achieve tumor control while maximally preserving the normal tissues from side effects. Unfortunately, the occurrence of local and distant complications is still elevated. Electrochemotherapy is a novel technique that combines the administration of anticancer agents to the application of permeabilizing pulses in order to increase the uptake of antitumor molecules. While its use in humans is still confined to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, in veterinary oncology this approach is rapidly becoming a primary treatment. This review summarizes the recent progresses in preclinical oncology and their possible transfer to humans

<it>IL-12</it> based gene therapy in veterinary medicine

<p>Abstract</p> <p>The use of large animals as an experimental model for novel treatment techniques has many advantages over the use of laboratory animals, so veterinary medicine is becoming an increasingly important translational bridge between preclinical studies and human medicine. The results of preclinical studies show that gene therapy with therapeutic gene encoding interleukin-12 (IL-12) displays pronounced antitumor effects in various tumor models. A number of different studies employing this therapeutic plasmid, delivered by either viral or non-viral methods, have also been undertaken in veterinary oncology. In cats, adenoviral delivery into soft tissue sarcomas has been employed. In horses, naked plasmid DNA has been delivered by direct intratumoral injection into nodules of metastatic melanoma. In dogs, various types of tumors have been treated with either local or systemic <it>IL-12</it> electrogene therapy. The results of these studies show that <it>IL-12</it> based gene therapy elicits a good antitumor effect on spontaneously occurring tumors in large animals, while being safe and well tolerated by the animals. Hopefully, such results will lead to further investigation of this therapy in veterinary medicine and successful translation into human clinical trials.</p

Metronomic chemotherapy for palliative treatment of malignant oral tumors in dogs

The aim of this study was to evaluate the efficacy of metronomic chemotherapy in the palliative treatment of various malignant oral tumors in dogs. Our focus was to determine the effect of treatment on local disease control and to assess the tolerability and safety of the treatment in dogs with various oral malignancies. Metronomic chemotherapy with cyclophosphamide was used to treat 12 dogs and was combined with non-steroidal anti-inflammatory drugs in 6/12 (50%) of dogs. A clinical benefit was observed in 6/12 (50%) patients 1 month and in 4/12 (33%) 3 months after treatment initiation. The median survival time of the dogs was 155 days (range 21–529 days). At the end of the observation period, the disease had progressed in 10/12 (83.3%) of the patients. Sterile hemorrhagic cystitis was the most commonly reported side effect of treatment, occurring in 4/12 (33.3%) dogs. The results of our study suggest that metronomic chemotherapy with cyclophosphamide can be, in a subset of dogs, beneficial in the palliation of malignant oral tumors