Topic:Melanoma
Melanoma in horses is a type of skin tumor commonly observed in gray horses, although it can occur in horses of any color. These tumors are typically found in areas such as the under-tail region, perineum, and around the lips and eyes. While many melanomas remain benign, some can become malignant and metastasize to other parts of the body. The underlying causes of melanoma in horses are not fully understood, but genetic factors and coat color are known to influence their development. Diagnosis often involves clinical examination and, in some cases, biopsy or imaging techniques. This page compiles peer-reviewed research studies and scholarly articles that explore the prevalence, diagnosis, progression, and management of melanoma in equine populations.
Constitutive activation of the ERK pathway in melanoma and skin melanocytes in Grey horses. Constitutive activation of the ERK pathway, occurring in the vast majority of melanocytic neoplasms, has a pivotal role in melanoma development. Different mechanisms underlie this activation in different tumour settings. The Grey phenotype in horses, caused by a 4.6 kb duplication in intron 6 of Syntaxin 17 (STX17), is associated with a very high incidence of cutaneous melanoma, but the molecular mechanism behind the melanomagenesis remains unknown. Here, we investigated the involvement of the ERK pathway in melanoma development in Grey horses. Methods: Grey horse melanoma tumours, cell lines ...
A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy in tumor-bearing equidae. The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. Objective: To provide preliminary evidence of the efficacy of doxorubicin in tumor-bearing horses, explore drug pharmacokinetics profile, and estimate period of risk of exposure to drug residues. Methods: Twelve horses with 37 tumors. Methods: Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m(2) and 4 horses received 4 of 6 treatment cycles at 70 mg/m(2) . Clinical signs, tumor responses, and toxicoses...
Surgical Management of Penile and Preputial Neoplasms in Equine with Special Reference to Partial Phallectomy. Penile and preputial neoplasia in horses occurs infrequently and represents diagnostic and therapeutic challenges. The present study was carried out on a total number of 21 equids (14 stallions and 7 donkeys) suffered from different penile and preputial neoplasia. Diagnosis of neoplasms was based up on history of the case, clinical examination as well as histopathological evaluation. Animals with penile and preputial neoplasms were underwent local excision and partial phallectomy with a slightly modified version of the techniques described by William's. The diagnosed neoplasms were penile and ...
Establishment and characterization of a primary and a metastatic melanoma cell line from Grey horses. The Grey horse phenotype, caused by a 4.6 kb duplication in Syntaxin 17, is strongly associated with high incidence of melanoma. In contrast to most human melanomas with an early onset of metastasis, the Grey horse melanomas have an extended period of benign growth, after which 50% or more eventually undergo progression and may metastasize. In efforts to define changes occurring during Grey horse melanoma progression, we established an in vitro model comprised of two cell lines, HoMel-L1 and HoMel-A1, representing a primary and a metastatic stage of the melanoma, respectively. The cell lines ...
Coat color genotypes and risk and severity of melanoma in gray quarter horses. Both graying and melanoma formation in horses have recently been linked to a duplication in the STX17 gene. This duplication, as well as a mutation in the ASIP gene that increases MC1R pathway signaling, affects melanoma risk and severity in gray horses. Objective: To determine if melanoma susceptibility in gray Quarter Horses (QH) is lower than gray horses from other breeds because of decreased MC1R signaling resulting from a high incidence of the MC1R chestnut coat color allele in the QH population. Methods: A total of 335 gray QH with and without dermal melanomas. Methods: Blood or hair roo...
[Metastatic malignant melanoma with spinal cord compression and resulting recumbency ante partum in a mare. A case report]. The case report describes a narrowing of the spinal canal in the lumbar and sacroiliac regions with entailing acute recumbency in a nearterm 17-year-old Welsh B Pony mare. The reason for recumbency was metastases of a malignant melanoma in the spinal canal of the lumbo-sacral region, where the tumour had invaded the dura mater and applied severe pression on the spinal cord over a length of 10 cm. Clinical findings, laboratory diagnostics, pathological-anatomical and histopathological findings are presented.
Complex inheritance of melanoma and pigmentation of coat and skin in Grey horses. The dominant phenotype of greying with age in horses, caused by a 4.6-kb duplication in intron 6 of STX17, is associated with a high incidence of melanoma and vitiligo-like skin depigmentation. However, the progressive greying and the incidence of melanoma, vitiligo-like depigmentation, and amount of speckling in these horses do not follow a simple inheritance pattern. To understand their inheritance, we analysed the melanoma grade, grey level, vitiligo grade, and speckling grade of 1,119 Grey horses (7,146 measurements) measured in six countries over a 9-year period. We estimated narrow sense...
Cutaneous neoplastic lesions of equids in the central United States and Canada: 3,351 biopsy specimens from 3,272 equids (2000-2010). To identify epidemiological trends in cutaneous neoplasms affecting equids in central North America and compare them with previously reported trends. Methods: Retrospective case series. Methods: 3,351 cutaneous biopsy specimens from 3,272 equids with a neoplastic diagnosis. Methods: Diagnostic reports from 2 diagnostic laboratories (Colorado State University and Prairie Diagnostic Services Inc) were reviewed for frequency of specific lesions and epidemiological trends. Variables included in analyses (if known) were age, sex, breed, geographic location, date of diagnosis, location of neoplasm o...
EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology. Equine penile papillomas, in situ carcinomas, and invasive carcinomas are hypothesized to belong to a continuum of papillomavirus-induced diseases. The former ones clinically present as small grey papules, while the latter 2 lesions are more hyperplasic or alternatively ulcerated. To test the hypothesis that these lesions are papillomavirus-induced, samples of 24 horses with characteristic clinical and histologic findings of penile papillomas or in situ or invasive squamous cell carcinomas were collected. As controls, 11 horses with various lesions--namely, Balanoposthitis (6 cases), melanoma ...
Nonseptic diseases associated with the hoof complex: keratoma, white line disease, canker, and neoplasia. This article addresses nonseptic diseases associated with the hoof complex, namely keratoma, white line disease, canker, and neoplasia. Keratoma is an uncommon cause of lameness, which may be surgically removed. White line disease, a keratolytic process on the solar surface of the hoof, is treated with therapeutic farriery and resection of the hoof wall when appropriate. Equine canker is an infectious process that results in development of a chronic hypertrophy of the horn-producing tissues. Neoplasia involving the equine foot is rare, and melanoma is the most common type of neoplasm reported....
Copy number expansion of the STX17 duplication in melanoma tissue from Grey horses. Greying with age in horses is an autosomal dominant trait, associated with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We recently identified a 4.6 kb duplication in STX17 to be associated with the phenotype. The aims of this study were to investigate if the duplication in Grey horses shows copy number variation and to exclude that any other polymorphism is uniquely associated with the Grey mutation. Results: We found little evidence for copy number expansion of the duplicated sequence in blood DNA from Grey horses. In contrast, clear evidence for copy number expansio...
RACK1, a clue to the diagnosis of cutaneous melanomas in horses. Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses. Results: Using immunofluorescence, we report here that both MITF ...
[Diagnostic assessment of peritoneal fluid cytology in horses with abdominal neoplasia]. To evaluate the diagnostic value of peritoneal fluid (PF) cytology for clinical diagnosis of abdominal neoplasia in horses. Methods: Ten horses with histopathologically confirmed abdominal neoplasia, in which a PF analysis was performed, were included in this retrospective study. PF was analyzed for total protein concentration and a nucleated cell count was performed. Using cytological criteria of malignancy, the PF samples were evaluated regarding their probability of malignancy. Results: Cytologic classification of cells according to criteria of malignancy allowed a positive cytologic diagno...
In vivo induction of interferon gamma expression in grey horses with metastatic melanoma resulting from direct injection of plasmid DNA coding for equine interleukin 12. Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 µg naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples w...
[Molecular basis and applicability in equine color genetics]. Coat color can be used not only in identifying individuals and species, but also in diagnosing certain diseases. The coat color of horse mainly depends on the distribution and proportion of eumelanin and phaeomelanin, generated by melanocytes, which are regulated by the genes such as MC1R, ASIP, KIT, TYRP, and EDNRB. In addition, STX17, MATP, and PMEL17 also play a role in the formation of coat color of horse. In this review, the action mechanism of candidate genes for coat color and association of DNA sequence polymorphism of these candidate genes with color pattern phenotypes and melanoma we...
Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses. Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmi...
Equine periocular neoplasia: current concepts in aetiopathogenesis and emerging treatment modalities. Neoplastic adnexal disease represents one of the most frequently encountered and therapeutically challenging ophthalmic problems of horses. This paper reviews current concepts in equine periocular neoplasia. Specifically, a literature-based review of the aetiopathogenesis of the most common tumours to affect the equine eyelid (squamous cell carcinoma, sarcoid, melanoma and lymphosarcoma) is provided. Current and emerging treatment modalities, including photodynamic therapy, are reviewed.
Cisplatin: a review of toxicities and therapeutic applications. Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The antineoplastic activity occurs from DNA cross-links and adducts, in addition to the generation of superoxide radicals. Nephrotoxicity is the most well-known and potentially most clinically significant toxicity. Unfortunately, the mechanism for cisplatin nephrotoxicity has not been completely elucidated; however, many theories have been developed. Other toxicities include gastrointestinal, myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the most accepted way to prevent cisplatin nephrot...
Epibulbar melanoma in a foal. A case of epibulbar melanoma in a 6-month-old, gelded, chestnut Hanoverian foal is reported. The location and clinical appearance upon initial presentation led to the tentative diagnosis of staphyloma or a congenital mass of unknown origin. An attempt was made to surgically excise the mass under general anesthesia, but due to its infiltrative nature and intraoperative appearance, most, but not all was removed without compromising the integrity of the globe. Histopathological evaluation revealed a multinodular to packeted, poorly demarcated, unencapsulated, infiltrative exophytic melanocytic ne...
Isolation, establishment, and characterization of ex vivo equine melanoma cell cultures. Gray horses spontaneously develop metastatic melanomas that resemble human disease, and this is often accompanied with metastasis to other organs. Unlike in other species, the establishment of primary equine melanoma cultures that could be used to develop new therapeutic approaches has remained a major challenge. The purpose of the study was to develop a protocol for routine isolation and cultivation of primary equine melanocytes. Melanoma tissues were excised from 13 horses under local anesthesia, mainly from the perianal area. The melanoma cells were isolated from the melanoma tissue by seri...
Cyclooxygenase-2 expression in equine tumors. The enzyme cyclooxygenase-2 (COX-2) is expressed in some tumor and stromal tissues, and catalyzes production of prostaglandins with growth stimulatory, antiapoptotic, proangiogenic, and immunosuppressive properties. Pharmacologic inhibition of COX-2 is associated with antitumor activity in various human and canine malignancies. The purpose of this study was to assess COX-2 expression in a series of equine sarcoids, melanomas, and squamous-cell carcinomas (SCC). COX-2 expression was assessed in formalin-fixed paraffin-embedded tissues from 14 sarcoids, 11 melanomas, and 37 SCC that represent va...
A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse. In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gra...
Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Preputial and penile tumours are more common in horses than in other domestic animals, but no large surveys of male horses with tumours of the external genitalia are available. Objective: To present a retrospective analysis of male horses with neoplasms of the external genitalia. Methods: The penile and preputial tumours of 114 horses were evaluated. Data recorded included age, gelding or stallion and breed; type and site of lesion; involvement of regional lymph nodes; histopathology (including grading of squamous cell carcinoma); and results of radiographic examination of the thorax. Results:...
Long-term outcome associated with intratumoral chemotherapy with cisplatin for cutaneous tumors in equidae: 573 cases (1995-2004). To determine outcome associated with cutaneous tumors treated via intratumoral chemotherapy with cisplatin and identify risk factors affecting local tumor control and complications in equidae. Methods: Retrospective case series. Methods: 573 equidae with 630 cutaneous tumors. Methods: Medical records of horses, mules, donkeys, and ponies with cutaneous tumors treated via intratumoral chemotherapy with cisplatin were analyzed. Results: 549 horses, 13 mules, 8 donkeys, and 3 ponies with 630 histologically confirmed cutaneous tumors were included. Tumors included sarcoids (n = 409), squamous cell...
Use of cisplatin-containing biodegradable beads for treatment of cutaneous neoplasia in equidae: 59 cases (2000-2004). To determine outcome for equids with cutaneous neoplasms treated with cisplatin-containing biodegradable beads, alone or in conjunction with debulking. Methods: Retrospective case series. Methods: 56 horses, 1 zebra, 1 donkey, and 1 mule. Methods: Medical records were reviewed. Follow-up information was obtained through telephone conversations with owners and trainers of the animals. Results: 22 tumors were sarcoids, 6 were fibrosarcomas, 1 was a fibroma, 2 were peripheral nerve sheath tumors, 11 were squamous cell carcinomas, 14 were melanomas (13 gray horses and 1 bay horse), 1 was a lymphos...