Search Results (6)

Equine melanocytic tumors are common and have an unusual benign behavior with low invasiveness and metastatic rates. However, tumoral mass growth is usually a concern that can have life-threatening consequences. COX-2 is related to oncogenesis, promoting neoplastic cell proliferation, invasion, and metastasis. The aim of this study was to evaluate the immunohistochemical expression of COX-2 in equine melanocytic tumors. Through extension and intensity of labeling, 39 melanocytomas and 38 melanomas were evaluated. Of the malignant tumors, 13.2% were negative and 63.2% presented a low COX-2 expression. Only 6 malignant tumors presented >50% of labeled cells, 18 malignant and 8 benign had an expression between 21 and 50%, 8 malignant and 3 benign tumors had an expression between 6 and 20%, 1 malignant tumor had an expression between 1 and 5%, and 5 malignant and 28 benign tumors had no expression. Malignant tumors showed higher COX-2 expression than did benign tumors, with statistically significant differences. The low levels of COX-2 may be one of the molecular reasons for the presence of expansive mass growth instead of the invasive pattern of other species, which is related to high COX-2 levels. Full article

Malignant melanomas (MMs) are the abnormal proliferation of melanocytes and are one of the lethal skin cancers in humans, equines, and canines. Accordingly, MMs in companion animals can serve as naturally occurring animal models, completing conventional cancer models. The common constitutive activation of the MAPK and PI3K pathways in MMs has been described in all three species. Targeting the related pathways is considered a potential option in comparative oncologic approaches. Herein, we present a cross-species comparative analysis exposing a set of ten melanoma cell lines (one human, three equine, and six canine) derived from primary tumors or metastasis to a pan-RAF and RAF dimer inhibitor (LY3009120). Cellular response (proliferation, biomass, metabolism, early and late apoptosis/necrosis, and morphology) and the presence of pathogenic single-nucleotide variants (SNVs) within the mutational hotspot genes BRAF exon 11 and 15, NRAS exon 2 and 3, KRAS exon 2, and KIT exon 11 were analyzed. This study showed that equine malignant melanoma (EMM) cells (MelDuWi) harbor the KRAS p.Q61H mutation, while canine malignant melanoma (CMM) cells (cRGO1 and cRGO1.2) carry NRAS p.G13R. Except for EMM metastasis cells eRGO6 (wild type of the above-mentioned hotspot genes), all melanoma cell lines exhibited a decrease in dose dependence after 48 and 72 h of exposure to LY3009120, independent of the mutation hotspot landscape. Furthermore, LY3009120 caused significant early apoptosis and late apoptosis/necrosis in all melanoma cell lines except for eRGO6. The anti-tumor effects of LY3009120 were observed in nine melanoma cell lines, indicating the potential feasibility of experimental trials with LY3009120. The present study reveals that the irradiation-resistant canine metastasis cells (cRGO1.2) harboring the NRAS p.G13R mutation are significantly LY3009120-sensitive, while the equine metastases-derived eRGO6 cells show significant resistance to LY3009120, which make them both valuable tools for studying resistance mechanisms in comparative oncology. Full article

Currently available treatments for equine melanocytic tumors have limitations, mainly due to mass localization and dimension, or the presence of metastases. Therefore, a search for new therapies is necessary. Programmed cell death-ligand 1 (PD-L1) is expressed by several tumors, blocking T cell-mediated elimination of the tumor cells by binding to programmed cell death protein 1 (PD-1). A novel therapeutic approach using PD-1/PD-L1 blockade in human melanoma resulted in tumor regression and prolonged tumor-free survival. This study aimed to evaluate the immunohistochemical expression of PD-L1 in equine melanocytic tumors. A total of 77 melanocytic tumors were classified as benign or malignant and evaluated by extension of labeling. A total of 59.7% of the tumors showed >50% of immunolabeled cells. Regarding malignant tumors, 24/38 tumors presented >50% of labeled cells, 13 tumors presented between 25–50% and one tumor presented <10%. Regarding benign tumors, 22/39 tumors presented >50% of labeled cells, nine tumors presented 25–50%, three tumors presented 10–25%, two tumors presented <10% and three tumors did not present expression. Our results suggest that PD-L1 blockade may be a potential target for immunotherapy in equine melanocytic tumors and that future clinical research trials into the clinical efficacy of the anti-PD-L1 antibody are necessary. Full article

Melanocytic tumors are an important neoplastic disease in human and veterinary medicine, presenting large differences regarding tumor behavior between species. In horses, these tumors present a prolonged benign behavior, with rare invasiveness and metastases. In humans and small animals, invasion and metastasis have been associated with an Epithelial-Mesenchymal Transition, where the loss of E-cadherin expression plays a key role in tumor progression. This process and the role of E-cadherin have not yet been evaluated in equine melanocytic tumors. This study aimed to assess the immunolabeling of E-cadherin in equine melanocytic tumors and relate this with clinicopathological variables. A total of 72 equine melanocytic tumors were classified as benign and malignant and evaluated by immunohistochemistry for E-cadherin expression. A different pattern of immunostaining was found, contrasting with other species. A total of 69.4% of tumors presented raised immunolabeling of E-cadherin, with 70.7% of melanomas remaining with high expression. The typical loss of immunostaining was not seen in malignant melanomas and no differences were found between benign and malignant melanomas regarding E-cadherin immunostaining. The high immunolabeling of E-cadherin may contribute to the low invasiveness of these tumors, and it is in accordance with the benign behavior of equine melanoma and with the genetic factors associated with its development. Full article

Adult grey horses have a high incidence of melanocytic tumors. This article narratively reviews the role of some genetic features related to melanoma formation in horses, such as STX17 mutation, ASIP or MITF alterations, and the link between the graying process and the development of these tumors. A clear system of clinical and pathological classification of melanocytic tumors in naevus, dermal melanoma, dermal melanomatosis and anaplastic malignant melanoma is provided. Clinical and laboratorial methods of diagnosing are listed, with fine needle aspiration and histopathology being the most relevant. Relevance is given to immunohistochemistry, describing potentially important diagnostic biomarkers such as RACK1 and PNL2. Different therapeutical options available for equine practitioners are mentioned, with surgery, chemotherapy and electroporation being the most common. This article also elucidatesnew fields of research, perspectives, and new therapeutic targets, such as CD47, PD-1 and COX-2 biomarkers. Full article

The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form. Full article