Topic:Cancer
Cancer in horses encompasses a range of neoplastic diseases that affect various tissues and organs in equine species. These conditions involve the uncontrolled growth of abnormal cells, which can form tumors and potentially spread to other parts of the body. Common types of cancer in horses include sarcoids, squamous cell carcinoma, and melanoma, each with distinct characteristics and clinical presentations. Diagnosis often involves a combination of physical examination, imaging techniques, and histopathological analysis. Treatment options vary based on the type and stage of cancer and may include surgical intervention, chemotherapy, and radiation therapy. This page compiles peer-reviewed research studies and scholarly articles that explore the epidemiology, pathophysiology, diagnostic methods, and treatment strategies for cancer in horses.
Use of the Intratumoural Anticancer Drug Tigilanol Tiglate in Two Horses. Tigilanol tiglate is a novel small molecule approved as a veterinary pharmaceutical in Europe for intratumoural treatment of non-metastatic, non-resectable canine mast cell tumors. The drug has a "tumor agnostic" mode of action associated with induction of an acute inflammatory response at the treatment site, immune cell recruitment, and disruption of tumor vasculature. Consequently, tigilanol tiglate has potential in treating a range of tumor types in humans and companion animals. However, it is likely that species-specific dosing and concomitant medication protocols will be required, especia...
Concentration profiles and safety of topically applied betulinic acid and NVX-207 in eight healthy horses-A randomized, blinded, placebo-controlled, crossover pilot study. The naturally occurring betulinic acid (BA) and its derivative NVX-207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX-207 in equine skin and assess the compounds' local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX-207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven-d...
Prevalence and Prognostic Impact of Equus caballus Papillomavirus Type 2 Infection in Equine Squamous Cell Carcinomas in Western Canadian Horses. Equus caballus papillomavirus type-2 (EcPV-2) has been proposed as a causal factor in equine genital squamous cell carcinoma (SCC). This study had 2 objectives: first, calculate the frequency of papillomavirus (PV) and EcPV-2 infection in papillomas, carcinomas in situ (CIS), and SCCs in Western Canadian horses; and second, determine if EcPV-2 status of equine SCCs is associated with overall survival (OS). EcPV-2 status of 115 archived tissue samples, spanning 6 years, was determined using broad spectrum (MY09/11) and EcPV-2-specific polymerase chain reaction (PCR) assays, EcPV-2-E6/E7 chromog...
Molecular approaches to equine sarcoids. Sarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto-oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA diff...
Spontaneously occurring melanoma in animals and their relevance to human melanoma. In contrast to other cancer types, melanoma incidence has been increasing over the last 50 years, and while it still represents less than 5% of all cutaneous malignancies, melanoma accounts for the majority of skin cancer deaths, due to its propensity to metastasise. Whilst melanoma most commonly affects the skin, it can also arise in mucosal surfaces, the eye, and the brain. For new therapies to be developed, a better understanding of the genetic landscape, signalling pathways, and tumour-microenvironmental interactions is needed. This is where animal models are of critical importance. The ...
Equine penile squamous cell carcinoma: expression of biomarker proteins and EcPV2. Equine penile squamous cell carcinoma (EpSCC) is a relatively common cutaneous neoplasm with a poor prognosis. In this study, we aimed to determine the protein expression and colocalisation of FRA1, c-Myc, Cyclin D1, and MMP7 in normal (NT), tumour (T), hyperplastic epidermis and/or squamous papilloma (Hyp/Pap), poorly-differentiated (PDSCC), or well-differentiated (WDSCC) EpSCC using a tissue array approach. Further objectives were to correlate protein expression to (i) levels of inflammation, using a convolutional neural network (ii) equine papillomavirus 2 (EcPV2) infection, detected using ...
Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model. We have investigated Amblyomin-X-treated horse melanomas to better understand its mode of action through transcriptome analysis and the in vivo model. Amblyomin-X is a Kunitz-type homologous protein that selectively leads to the death of tumor cells via ER stress and apoptosis, currently under investigation as a new drug candidate for cancer treatment. Melanomas are immunogenic tumors, and a better understanding of the immune responses is warranted. Equine melanomas are spontaneous and not so aggressive as human melanomas are, as this study shows that the in vivo treatment of encapsulated hors...
Calcium Electroporation of Equine Sarcoids. Sarcoids are common equine skin tumors where the risk of recurrence after treatment is high, and better treatment options are warranted. Calcium electroporation is a novel anti-cancer treatment where lethally high calcium concentrations are introduced into the cells by electroporation, a method where short high-voltage pulses induce transient permeabilization of the cell membrane. This study investigated the safety and long-term response of calcium electroporation on sarcoids. Thirty-two sarcoids in eight horses were included. The study suggested that calcium electroporation is a safe and feas...
A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus-2 Infection. Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As papillomavirus-2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. I...
Scapula fracture secondary to metastatic pulmonary carcinoma in a horse: Clinical, sonographic, radiographic, computed tomographic, and pathologic findings. A 20-year-old Quarter horse gelding was referred for evaluation of an acute onset non-weight-bearing right forelimb lameness. Marked soft tissue swelling was apparent over the right scapula and shoulder region; no crepitus was palpable. A complete transverse fracture of the scapular neck was suspected based on ultrasonography and radiographs were obtained to confirm the presumptive diagnosis. A complete, oblique fracture of the right scapular neck with mild cranial and proximal displacement of the distal fragment was detected. Computed tomography of the upper right forelimb was performed post-...
Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro. Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro. Results: BA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibrob...
Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study. equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well known that delta bovine papillomaviruses are their causative agents. We have recently shown the presence in equine sarcoids of abnormal vessel structures, which could cause a hypoxic condition. The aim of this study was to analyze the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in a subset of BPV positive equine sarcoids and explore the relationship with vascular endothelial growth factor (VEGF) expression. Results: 80% of equine sarcoids showed strong cytoplasmic staining in >60% of neoplastic f...
Bleaching melanin in formalin-fixed and paraffin-embedded melanoma specimens using visible light: a pilot study. In fluorescence microscopy, light radiation can be used to bleach fluorescent molecules in formalin-fixed and paraffin-embedded (FFPE) samples, in order to increase the ratio between signal of interest and background autofluorescence. We tested if the same principle can be exploited in bright field microscopy to bleach pigmented melanoma FFPE sections together with cell morphology maintenance. After dewaxing and rehydration, serial FFPE sections of a feline diffuse iris melanoma, a canine dermal melanoma, a gray horse dermal melanoma and a swine cutaneous melanoma were irradiated with visible ...
Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions. There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. Th...
Cauda equina syndrome in an ovarian malignant-mixed müllerian tumor with leptomeningeal spread. Leptomeningeal metastasis is extremely rare in patients with ovarian cancer, but should be considered in patients presenting with neurologic deficits such as cauda equine syndrome. Given its poor prognosis and lack of data currently on management, additional studies are needed to optimize treatment regimens and improve outcomes.
Epitope Analysis of an Antihorse Podoplanin Monoclonal Antibody PMab-219. Podoplanin (PDPN), which is a mucin-type membrane glycoprotein, is expressed on lymphatic endothelial cells and epithelial cells of many organs. PDPN is also overexpressed in several malignant cancers, and its expression is associated with cancer progression and poor prognosis. Human PDPN possesses three platelet aggregation-stimulating (PLAG) domains and the PLAG-like domain (PLD), which binds to C-type lectin-like receptor-2 (CLEC-2). Previously, we reported a novel antihorse PDPN (horPDPN) monoclonal antibody (mAb), PMab-219, using Cell-Based Immunization and Screening (CBIS) method. PMab-2...
Additional Evidence for DDB2 T338M as a Genetic Risk Factor for Ocular Squamous Cell Carcinoma in Horses. Squamous cell carcinoma (SCC) is the most common periocular cancer in horses and the second most common tumor of the horse overall. A missense mutation in damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met) was previously found to be strongly associated with ocular SCC in Haflinger and Belgian horses, explaining 76% of cases across both breeds. To determine if this same variant in DDB2 contributes to risk for ocular SCC in the Arabian, Appaloosa, and Percheron breeds and to determine if the variant contributes to risk for oral or urogenital SCC, histologically confirmed SCC c...
Occupational Exposures in an Equestrian Centre to Respirable Dust and Respirable Crystalline Silica. Sand-based products are regularly used as footing material on indoor equestrian arenas, creating a potential occupational exposure risk for respirable crystalline silica (RCS) for equestrian workers training and exercising horses in these environments. The objective of this study was to evaluate an equestrian worker's personal RCS and respirable dust (RD) exposure. Sixteen personal full-shift RD measurements were collected from an equestrian worker and analysed for RD, quartz and cristobalite. Geometric mean exposures of 0.12 mg m and 0.02 mg m were calculated for RD and RCS concentrations, re...
Treatment of Infiltrative Superficial Tumors in Awake Standing Horses Using Novel High-Frequency Pulsed Electrical Fields. Irreversible electroporation is a proven ablation modality for local ablation of soft tissue tumors in animals and humans. However, the strong muscle contractions associated with the electrical impulses (duration, 50-100 μs) requires the use of general anesthesia and, in most situations, application of neuromuscular blockade. As such, this technology is not used in an outpatient setting for ablating common cutaneous tumors (e.g., squamous cell carcinoma or melanoma) in humans or animals. Recently, high-frequency irreversible electroporation (H-FIRE) technology has been developed to enable ele...
Malignant Mesothelioma of the Vaginal Tunic and Peritoneum in a Young Stallion. Mesothelioma is a rare malignancy in horses. This report describes a case in which marked hemoperitoneum, moderate anemia, and moderate dependent edema were the presenting clinical signs in a 2-year-old Standardbred stallion with mesothelioma of the vaginal tunic. On necropsy, approximately 40 L of dark red fluid distended the abdomen. A dark red mass infiltrated and effaced the right pampiniform plexus, and red nodular masses were present multifocally on the parietal and visceral peritoneal surfaces. Histopathologically, the masses were composed of malignant spindle cells with a sarcomatoid ...
Treatment Options for Melanoma of Gray Horses. All gray horses inherited a single gene mutation, STX17G, that unbalances melanocyte behavior to cause graying and propensities to develop vitiligo and melanoma. The coat color genes ASIPa and MC1RE add risk such that relative likelihood of melanoma based on pregraying coat color is black > bay > chestnut. Melanomas begin at about 4 years. Locoregional control of melanoma masses depends on surgical removal and/or intralesional chemotherapy (possibly with adjunctive hyperthermia or electroporation). Systemic treatment is not evidence based but immunomodulators (cimetidine, levamisole) and ...
Bisphosphonate use in the horse: what is good and what is not? Bisphosphonates (BPs) are a family of molecules characterized by two key properties: their ability to bind strongly to bone mineral and their inhibitory effects on mature osteoclasts and thus bone resorption. Chemically two groups of BPs are recognized, non-nitrogen-containing and nitrogen-containing BPs. Non-nitrogen-containing BPs incorporate into the energy pathways of the osteoclast, resulting in disrupted cellular energy metabolism leading to cytotoxic effects and osteoclast apoptosis. Nitrogen-containing BPs primarily inhibit cholesterol biosynthesis resulting in the disruption of intrac...
Calcium electroporation: The bioelectrochemical treatment of spontaneous equine skin tumors results in a local necrosis. Electrochemotherapy (ECT) is an anticancer bioelectrochemical therapy where electrical field pulses (electropermeabilization) increase intracellular concentration of antitumor drugs. The procedure is very effective against skin tumors. The restrictive regulations concerning anticancer drugs in veterinary medicine limit use of ECT. Electroporation with calcium (Electroporation Calcium Therapy)(ECaT) was proved to be effective in vivo on induced tumors in laboratory animals. This study evaluated the effects of ECaT in equine sarcoids (spontaneous skin tumors) on an animal cohort. Pulse parameter...
Methylation Marks of Blood Leukocytes of Native Hucul Mares Differentiated in Age. Horses are one of the longest-living species of farm animals. Advanced age is often associated with a decrease in body condition, dysfunction of immune system, and late-onset disorders. Due to this, the search for new solutions in the prevention and treatment of pathological conditions of the advanced age of horses is desirable. That is why the identification of aging-related changes in the horse genome is interesting in this respect. In the recent years, the research on aging includes studies of age-related epigenetic effects observed on the DNA methylation level. We applied reduced represent...
Standing Hand-Assisted Laparoscopic Diagnosis and Treatment of a Rare Case of Uterine Adenocarcinoma in an 18-Year-Old Mare. An 18-year-old French Trotter mare was presented to the Clinique Equine, Ecole Nationale Vétérinaire d'Alfort, for exploration of a 3-month-duration vaginal bleeding. A transrectal ultrasound examination identified a mass within the right uterine horn wall, which had been suspected during transrectal palpation. It was described as a firm heterogeneous intramural mass (7 × 12 cm) in the right uterine horn, located few centimeters cranially to the bifurcation. Hysteroscopy confirmed the ulcerated and irregular shape of the mass. A standing hand-assisted flank laparoscopy was performed to ca...
RNA-seq analysis in equine papillomavirus type 2-positive carcinomas identifies affected pathways and potential cancer markers as well as viral gene expression and splicing events. Equine papillomavirus type 2 (EcPV2) was discovered only recently, but it is found consistently in the context of genital squamous cell carcinomas (SCCs). Since neither cell cultures nor animal models exist, the characterization of this potential disease agent relies on the analysis of patient materials. To analyse the host and viral transcriptome in EcPV2-affected horses, genital tissue samples were collected from horses with EcPV2-positive lesions as well as from healthy EcPV2-negative horses. It was determined by RNA-seq analysis that there were 1957 differentially expressed (DE) host genes...
A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for ocular squamous cell carcinoma in Belgian horses. Belgian horses are commonly affected with ocular squamous cell carcinoma (SCC), the most common cancer of the equine eye. A missense mutation in damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) has been established as a recessive genetic risk factor for ocular SCC in the Haflinger breed. A sample of Belgian horses with unknown SCC phenotype was shown to possess this variant at a similar frequency to the Haflinger breed. Retrospective studies indicate that chestnut coat colour may predispose to the development of SCC. Objective: To determine if DDB2 c.1013C>T is a risk ...
Mediastinal Ectopic Thyroid Carcinoma and Concurrent Multinodular Pulmonary Fibrosis in a Horse. A 30-year-old Standardbred gelding was referred for chronic pleural effusion. Thoracic ultrasound revealed marked bilateral pleural effusion and a large heterogeneous mass within the cranial mediastinum, which extended from the right 5th to the 11th intercostal space. Subsequently, on thoracic radiographs, the cranial mediastinal mass was confirmed, and a nodular interstitial pattern was identified in the lungs. Because of progressive clinical deterioration of the patient, the owners elected humane euthanasia and necropsy was performed. The mediastinal mass was consistent with an ectopic thyro...
An unusual case of giant cell tumor of soft parts in an American Warmblood horse. Fine needle aspiration and tissue biopsy samples were taken from a subcutaneous mass in the cranial stifle region of a 10-yr-old horse. Key cytologic features included numerous mildly to moderately pleomorphic histiocytic cells admixed with mononuclear inflammatory cells, occasional fibroblasts, multinucleated cells, and hemosiderin-laden macrophages. Based on these features, cytologic differentials included granulomatous inflammation with reactive fibroplasia, histiocytic sarcoma, giant cell tumor of soft parts (GCTSPs), and giant cell tumor of bone. The tissue biopsy supported a diagnosis of...
Differentially expressed microRNAs, including a large microRNA cluster on chromosome 24, are associated with equine sarcoid and squamous cell carcinoma. The aim of this study was to investigate microRNA (miRNA) differential expression in the two most common equine skin tumours, equine sarcoid (ES) and squamous cell carcinoma (SCC), and its potential influence on the tumour microenvironment at post-transcriptional level. We investigated miRNA fingerprints in four subgroups: mild (ESM) and aggressive (ESA) ES and ocular SCC (oSCC) and genital SCC (gSCC). Three tumours and three control samples were included in each of the four subgroups. Following next generation sequencing, miRNA differential expression analysis using DESeq2 was carried out. Pa...