Electrochemotherapy for the treatment of cutaneous solid tumors in equids: A retrospective study.

Background: Electrochemotherapy (ECT) promotes the increased uptake of antitumor agents through the administration of permeabilizing electric pulses, thus enhancing chemotherapy effectiveness. Aim: Our study aimed to describe the tolerability and efficacy of ECT alone or in association with surgery to manage solid neoplasms in equids. Methods: Medical records of equids with a diagnosis of malignant tumors treated with ECT alone or in combination with surgery were retrospectively evaluated. Each equid received local treatment within the tumors or the tumors' bed with cisplatin at the dose of 0.5 mg/cm2. Trains of permeabilizing biphasic electric pulses were then applied under spinal or general anesthesia. Results: Sixteen equids were enrolled in this study. There were nine melanoma cases, four fibrosarcoma, and three squamous cell carcinoma. Of those 16 equids, 7 received ECT for treatment of intraoperative local disease, while in 9 cases, ECT was the only treatment modality. The seven equids treated with the combination of ECT and surgery still have no evidence of disease at different times ranging from 9 to 60 months. The remaining nine had the following responses: two complete remissions, five partial responses, one stable disease, and one progressive disease. The treatment was well-tolerated, and local side effects were minimal. No systemic effects were documented. Conclusion: This retrospective study suggests that ECT may be beneficial for equids with solid neoplasms and could be a useful addition to the current therapeutic options considering its low cost, limited toxicity, and ease of administration.

Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells.

We investigated the chemosensitizing effect of electroporation (EP), which, using electrical pulses, permeabilizes cancer cells to drugs. The study involved two human hypopharyngeal and tongue carcinoma cell lines. The surface and intracytoplasmic expression of P-gp were evaluated by flow cytometry, demonstrating that both lines were intrinsically resistant. After establishing the optimal dose of mitomycin C (MMC) to be used, in combination with EP, we showed, by both MTT assay and optical and electron scanning microscopy, the potentiating cytotoxic effect of EP with MMC compared to single treatments. Flow cytometry showed that the cytotoxicity of EP + MMC was due to the induction of apoptosis. In addition to verifying the release of cytochrome C in EP + MMC samples, we performed an expression analysis of caspase-3, caspase-9, Akt, pAkt, HMGB1, LC3I, LC3II, p62, Beclin1, and associated proteins with both apoptotic and autophagic phenomena. Our results were confirmed by two veterinary patients in whom the EP + MMC combination was used to control margins after the resection of corneal squamous carcinoma. In conclusion, we affirmed that the effect for which EP enhances MMC treatment is due to the inhibition of the autophagic process induced by the drug in favor of apoptosis.

Paraoxonase-1 activity evaluation as a diagnostic and prognostic marker in horses and foals.

BACKGROUND: In several species, paraoxonase-1 (PON-1) decreases during inflammation, because of the presence of oxidative stress; its measurement recently has been validated in horses, but its role as a clinical biomarker is unknown. OBJECTIVES: To evaluate sensitivity, specificity and likelihood ratio of PON-1 activity to identify systemic inflammatory response syndrome (SIRS)-positive horses or horses with a poor prognosis. ANIMALS: One hundred seventy-two blood samples from 58 sick horses from 3 different veterinary hospitals. METHODS: In a cross-sectional study, PON-1 activity was measured upon admission and at 24-hour intervals until discharge or death, and results were analyzed based on SIRS status and outcome. RESULTS: No statistically significant difference was found in median PON-1 activity between SIRS and non-SIRS cases or between survivors and non-survivors except for mares, in which PON-1 activity was significantly lower in SIRS-positive horses (P = .05). The sensitivity of PON-1 activity in identifying horses with SIRS or negative outcome was low (0.0%-46.2% depending on the examined group) but its specificity was high (87.0%-100.0%). However, when PON-1 is low, the likelihood of death is 2.40-3.89 times higher than the likelihood of survival. Repeated measurement of PON-1 after treatment does not predict outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: Evaluation of PON-1 activity in horses with inflammation might be advisable in the future, but only low activity at admission may be relevant in predicting SIRS or negative outcome.

Isolated limb perfusion electrochemotherapy for the treatment of an advanced squamous cell carcinoma of the hoof in a mare.

A twenty-year-old female saddle horse was referred for evaluation of a seven month, non-healing erosive lesion of the right hind hoof with proliferation and bleeding of the underlying soft tissues. This lesion had been twice surgically treated as a canker but rapidly recurred. Histological examination of the second excision revealed a well-differentiated squamous cell carcinoma. At presentation, the horse was mildly depressed, lame and partially non-weight-bearing on the right hind leg, which exhibited a 10 x 10 cm erosive and proliferative lesion remodeling the hoof. After completing staging procedures, the lesion was approached with surgery and intraoperative electrochemotherapy (ECT) administration of bleomycin in isolated limb perfusion. A second session of surgery and ECT was performed one month later, followed by three additional monthly sessions of ECT. During periodic recheck, the mare showed continuous improvement. One year after presentation, the mare was in complete remission and her gait markedly improved. ECT was well-tolerated and resulted in improved local control of a tumor in a challenging anatomical district.

Proton pump inhibitors for the treatment of cancer in companion animals.

The treatment of cancer presents a clinical challenge both in human and veterinary medicine. Chemotherapy protocols require the use of toxic drugs that are not always specific, do not selectively target cancerous cells thus resulting in many side effects. A recent therapeutic approach takes advantage of the altered acidity of the tumour microenvironment by using proton pump inhibitors (PPIs) to block the hydrogen transport out of the cell. The alteration of the extracellular pH kills tumour cells, reverses drug resistance, and reduces cancer metastasis. Human clinical trials have prompted to consider this as a viable and safe option for the treatment of cancer in companion animals. Preliminary animal studies suggest that the same positive outcome could be achievable. The purpose of this review is to support investigations into the use of PPIs for cancer treatment cancer in companion animals by considering the evidence available in both human and veterinary medicine.