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 systemicIL-12electrogene therapy. The results of these studies show thatIL-12based 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.
Chronic kidney disease (CKD) is characterized by chronic inflammation, which mediates the progressive replacement of functional nephrons by fibrotic tissue. Hemogram-derived inflammatory markers are known to serve as markers of pathological conditions; however, their diagnostic value in feline CKD is still unknown. The aim of this retrospective study was to investigate selected hemogram-derived inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammatory index (SII)) in cats at different clinical stages of CKD. Eighty-eight client-owned cats with CKD and thirty-two healthy control cats were included. Cats with CKD were divided into two groups: early CKD (IRIS stage 1 and 2; 62 cats) and progressed CKD (IRIS stage 3 and 4; 26 cats). The values of inflammatory markers were compared between the two CKD groups and the control group. All investigated hemogram-derived inflammatory markers were significantly (p < 0.05) greater in cats with advanced CKD than in those in the other two groups. Additionally, we demonstrated a statistically significant weak to moderate correlation between serum urea, creatinine, selected hematologic and urinary parameters, and the investigated inflammatory markers in cats with CKD. Chronic inflammation can be easily and inexpensively assessed with hemogram-derived markers.
Feline infectious peritonitis (FIP), once considered fatal disease with a mortality rate approaching 100%, has experienced a new therapeutic breakthrough in recent years. The aim of our study was to evaluate selected clinicopathological parameters before and after GS- 445124-based treatment of FIP in cats, which could serve as potential candidates for predicting treatment success and monitoring treatment progress. Pre-treatment haematological parameters in 32 treated cats showed moderate leukocytosis, neutrophilia, lymphopenia and anaemia, which normalised post-treatment. Pre-treatment values of haemogram-derived inflammatory markers (ratio of neutrophils to lymphocytes, platelets to lymphocytes, lymphocytes to monocytes and the systemic immune-inflammatory index) differed significantly from those in the healthy cats and between patients with effusive and non-effusive disease (p < 0.05). Post-treatment, only the ratio of lymphocytes to monocytes remained higher; the other three markers were comparable to the control group. The biochemical results showed characteristic abnormalities (e.g. hyperproteinaemia, hypoalbuminemia, hypergammaglobulinemia, hyperbilirubinemia), which normalised with treatment. Lactate dehydrogenase activities did not differ significantly before and after treatment, except in cats with a relapse and one non-responder, which had markedly elevated values at the time of diagnosis. Analysis of archived blood samples using ELISA revealed significant differences in concentration of acute-phase protein haptoglobin (p = 0.004) and pro-inflammatory cytokine tumour necrosis factor-α (p = 0.028) before and after therapy. Therapy didn’t elicit any statistically significant changes in concentrations of ferritin, interleukin- 1β and interleukin- 6. Our findings demonstrate that successful treatment of FIP leads to highly significant changes in most clinicopathological parameters, including haemogram-derived inflammatory markers. The latter could offer a simple, inexpensive and readily available alternative to the more commonly used acute phase proteins for monitoring FIP treatment. Successful therapy leads to a significant decrease in haptoglobin and an increase in tumour necrosis factor-α. In our study, cats with an unfavourable outcome showed a marked increase in lactate dehydrogenase activity before therapy, suggesting that this parameter could be a promising prognostic factor in larger studies.
Squamous cell carcinoma (SCC) is the most common nonodontogenic oral tumor in cats. In the jaw, it usually presents as an ulceroproliferative lesion associated with enlargement of the affected bone. This report describes the case of a cat in which clinical and radiographic findings of a mandibular swelling were suggestive of an aggressive process, but the oral mucosa was unaffected. The results of histopathological and immunohistochemical examination of the samples obtained from the intraosseous lesion were consistent with SCC. The animal was euthanized 5 months after initial presentation as a result of the severe progression of the disease, and no other primary tumors were identified at necropsy. Based on the clinicopathological, microscopic, and immunohistochemical staining features, as well as the absence of a primary tumor at a distant site, we propose that the term, solid type primary intraosseous SCC (PIOSCC), be used to describe this neoplasia, as it shares similar features with human PIOSCC.
Electrochemotherapy (ECT) and/or gene electrotransfer of plasmid DNA encoding interleukin-12 (GET pIL-12) are effective treatments for canine cutaneous, subcutaneous, and maxillofacial tumors. Despite the clinical efficacy of the combined treatments of ECT and GET, data on parameters that might predict the outcome of the treatments are still lacking. This study aimed to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) results of subcutaneous tumors differ between tumors with complete response (CR) and tumors without complete response (non-CR) in dogs treated with ECT and GET pIL-12. Eight dogs with a total of 12 tumor nodules treated with ECT and GET pIL-12 were included. DCE-US examinations were performed in all animals before and immediately after therapy as well as 8 h and 1, 3, and 7 days later. Clinical follow-up examinations were performed 7 and 14 days, 1 and 6 months, and 1 year after treatment. Numerous significant differences in DCE-US parameters were noted between tumors with CR and non-CR tumors; perfusion and perfusion heterogeneity were lower in CR tumors than in non-CR tumors. Therefore, studies with larger numbers of patients are needed to investigate whether DCE-US results can be used to predict treatment outcomes and to make effective decisions about the need for repeated therapy or different treatment combinations in individual patients.