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.
Equine sarcoid of the glans penis with bovine papillomavirus type 1 in a miniature horse (Falabella). A 23-year-old Falabella gelding kept in Tochigi, Japan, for more than 20 years presented with a recurrent mass of the glans penis that was first noticed about a year earlier. Partial phallectomy was performed with no adjunctive therapy for local regrowth of the mass. The horse was euthanized 3 months after surgery for urinary retention due to suspected regrowth. The resected mass affected the genital and urethral mucosa of the glans penis, and was diagnosed as equine sarcoid by histopathology and identification of bovine papillomavirus (BPV) DNA. Phylogenetic analysis of the BPV genome of the ...
Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation. Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription fac...
Expression of the Wilms’ tumour gene and its association with PPARβ/δ in healthy skin and melanoma of horses. The Wilms' tumour gene (WT1) has previously been described as an oncogene in several neoplasms of humans, including melanoma, and its expression increases cancer cell proliferation. Recent reports associate the expression of the PPARβ/δ gene (peroxisome proliferator-activated receptor beta/delta) with the downregulation of WT1 in human melanoma and murine melanoma cell lines. The aim of this work was to analyse the expression of WT1 and its association with PPARβ/δ in samples of healthy and melanoma-affected skin of horses by immunohistochemistry. WT1 protein expression was detected in hea...
Case Report of a Mare Diagnosed with a Metastatic Mammary Carcinoma after the Excision of a Recurrent Intraocular Neuroepithelial Tumor. A 24-year-old Irish Cob mare was presented with a peripheral iris mass, which was surgically resected and diagnosed as an undifferentiated neuroepithelial tumor. A few months later, a relapse occurred with histological features characterized by a more solid appearance and squamous differentiation. Subsequently, the mare was presented with rapidly spreading multiple subcutaneous masses and, at the onset of neurological signs, was humanely euthanized and subjected to a complete post mortem examination. The necropsy confirmed the presence of numerous widespread masses in the subcutaneous tissue, ...
Primary sinonasal malignant melanoma with systemic metastasis in a non-gray horse. A 27-y-old Anglo-Arabian gelding with bay coat color was presented with a swelling of the left maxillary region. Fenestration on the left maxilla revealed that the left maxillary sinus was filled with black-red tissue. A portion of the tissue was excised and diagnosed histologically as malignant melanoma. Genotyping of the STX17 gene for gray coat color revealed that the horse did not have the "gray" factor. The horse was euthanized ~3 mo after first presentation. During autopsy, a black-to-gray mass extended from the left nasal cavity to the surrounding paranasal sinus and invaded the hard ...
Epithelial to Mesenchymal Transition (EMT) in a Laryngeal Squamous Cell Carcinoma of a Horse: Future Perspectives. Squamous cell carcinoma (SCC) is one of the most frequent tumors of skin and muco-cutaneous junctions in the horse. Equine papillomavirus type 2 (EcPV2) has been detected in equine SCC of the oral tract and genitals, and recently also in the larynx. As human squamous cell carcinoma of the larynx (SCCL), it is strongly etiologically associated with high-risk papillomavirus (h-HPV) infection. This study focuses on tumor cells behavior in a naturally occurring tumor that can undergo the so-called epithelial to mesenchymal transition (EMT). A SCCL in a horse was investigated by immunohistochemistr...
Immunohistochemical Analysis of Programmed Death-Ligand 1 Expression in Equine Sarcoids. The aim of the study was to assess the expression of the immune checkpoint inhibitor programmed death-ligand 1 (PD-L1) in equine sarcoids (ES). Programmed death-ligand 1 is expressed by various cancer cells to block T cell-mediated elimination of tumor cells. Antibodies targeting human PD-L1 were tested by immunohistochemistry for their cross-reactivity with equine PD-L1 using formalin-fixed, paraffin-embedded tissues. Our results do not support an important role of PD-L1-mediated immune evasion in ES disease and hence do not offer a rationale for anti-PD-1/PD-L1-based immunotherapy against ES...
Two different clinical forms of squamous cell carcinoma (SCC) in the perineum and vulva of two mares. Genital malignant neoplasms in mares are relatively rare. The treatment involve surgical removal of the tumour masses, chemotherapy or both. Methods: Two elderly warmblood mares, aged 16 and 20 were presented in University Clinic with the lumpy lesions at the region of perineum and left labia. Surgical removals of tumour masses were performed on standing animals. Removed tissues were subjected to histopathological examination which confirmed SCC. Conclusions: Clinical and ultrasound examination of reproductive organs in both mares showed no inflammatory or neoplastic changes. Both mares healed...
Computed Tomographic and Histopathological Characteristics of 13 Equine and 10 Feline Oral and Sinonasal Squamous Cell Carcinomas. Squamous cell carcinoma (SCC) is the most common equine sinonasal and feline oral tumour. This study aimed to describe the computed tomographic and histopathological characteristics of equine and feline SCC. Thirteen horses and 10 cats that had been histopathologically diagnosed with oral or sinonasal SCC and had undergone computed tomography (CT) of the head were retrospectively included in the study. CT characteristics of the mass and involved structures were noted. Histological examinations were evaluated according to a human malignancy grading system for oral SCC, which considered four gra...
PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. Programmed death-1 (PD-1) is an immunoinhibitory receptor expressed on lymphocytes. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. In our previous studies, we have developed anti-bovine PD-L1 monoclonal antibodies (mAbs) and reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. Furthermore, we found that blocking antibodies that target PD-1 and PD-L1 restore T-cell functions and cou...
A novel DDB2 mutation causes defective recognition of UV-induced DNA damages and prevalent equine squamous cell carcinoma. Squamous cell carcinoma (SCC) occurs frequently in the human Xeroderma Pigmentosum (XP) syndrome and is characterized by deficient UV-damage repair. SCC is the most common equine ocular cancer and the only associated genetic risk factor is a UV-damage repair protein. Specifically, a missense mutation in horse DDB2 (T338M) was strongly associated with both limbal SCC and third eyelid SCC in three breeds of horses (Halflinger, Belgian, and Rocky Mountain Horses) and was hypothesized to impair binding to UV-damaged DNA. Here, we investigate DDB2-T338M mutant's capacity to recognize UV lesions in ...
Outcome of external beam radiotherapy for treatment of noncutaneous tumors of the head in horses: 32 cases (1999-2015). The long-term outcomes of external beam radiotherapy for treatment of noncutaneous tumors of the head in horses is unknown. Objective: To report the long-term outcomes for treatment of noncutaneous tumors of the head of horses, and report short and long-term clinical adverse effects. Methods: Thirty-two horses treated in 2 referral hospitals. Methods: In this retrospective study, medical records of horses receiving radiation therapy for noncutaneous tumors between 1999 and 2015 were reviewed. Signalment, tumor type, treatment protocol, tumor control duration, and survival were recorded. Kaplan...
Circulating melanin-containing cells and neutrophils with phagocytized melanin granules in a horse with disseminated melanoma. An 18-year-old, grey, Thoroughbred Cross gelding was referred to the Cummings School of Veterinary Medicine at Tufts University following a 3-week history of low-grade fever of unknown origin, distal limb swelling, and weight loss. Clinical examination identified a few black, round, smooth nodules along the ventral aspect of the proximal tail. Transabdominal ultrasound showed a markedly enlarged heterogenous spleen, hyperechoic liver nodules, and evidence of peritonitis with fibrin deposition. A mature neutrophilia was noted on complete blood count with variable numbers of phagocytized granule...
In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer. Equine sarcoid (ES) is the most prevalent skin tumor in equids worldwide. Additionally, aging grey horses frequently suffer from equine malignant melanoma (EMM). Current local therapies targeting these skin tumors remain challenging. Therefore, more feasible topical treatment options should be considered. In order to develop a topical therapy against ES and EMM, betulinyl-bis-sulfamate and NVX-207, derivatives of the naturally occurring betulin and betulinic acid, respectively, were evaluated for their antiproliferative (crystal violet staining assay), cytotoxic (MTS assay) and apoptotic (Anne...
The oncogenic pathways of papillomaviruses. Papillomaviruses are oncogenic DNA viruses and induce hyperplastic benign lesions of both cutaneous and mucosal tissues in their various hosts, including many domestic and wild animals as well as humans. There are some Papillomavirus genotypes that can infect hosts different from their own, such as BPV 1 and BPV 2 originated from cattle, which can also infect horses and are responsible for fibroblastic tumours in horses. This review article summarizes the origin and evolution of papillomaviruses as an etiological agent in the historical process. The main focus in this review is the evaluation ...
Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment. Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas , CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirme...
Bisphosphonates in veterinary medicine: The new horizon for use. Bisphosphonates (BPs) are characterized by their ability to bind strongly to bone mineral and inhibit bone resorption. However, BPs exert a wide range of pharmacological activities beyond the inhibition of bone resorption, including the inhibition of cancer cell metastases and angiogenesis and the inhibition of proliferation and apoptosis in vitro. Additionally, the inhibition of matrix metalloproteinase activity, altered cytokine and growth factor expression, as well as reductions in parameters of pain have also been reported. In humans, clinical BP use has transformed the treatment of post-m...
Surgical excision of a malignant metastatic melanoma located in a skeletal muscle of the lateral thorax of a horse. A 20-year-old grey Warmblood gelding that had history of dermal melanomatosis. To report surgical treatment of a 6-cm large malignant metastatic melanoma located in the cutaneous trunci muscle of the left lateral thorax of a horse. A 20-year-old grey Warmblood gelding was referred for evaluation of a large, rapidly growing, thoracic mass. Clinical examination revealed an ovoid, firm, non-painful, movable mass, approximately 6 cm in diameter, located in the cutaneous trunci muscle of the left lateral thorax. Multiple melanocytic nodules were also found at the perianal region and ventral tail. ...
An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species. Ultra-conserved non-coding elements (UCNEs) are genomic sequences that exhibit > 95% sequence identity between humans, mammals, birds, reptiles, and fish. Recent findings reported their functional role in cancer. The aim of this study was to evaluate the DNA methylation modifications of UNCEs in squamous cell carcinoma (SCC) from different mammal species. Fifty SCCs from 26 humans, 17 cats, 3 dogs, 1 horse, 1 bovine, 1 badger, and 1 porcupine were investigated. Fourteen feline stomatitis and normal samples from 36 healthy human donors, 7 cats, 5 dogs, 5 horses, 2 bovines and 1 badger were c...
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...