Journal articles: 'Canine oral melanoma'

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Bergman, Philip J. "Canine Oral Melanoma." Clinical Techniques in Small Animal Practice 22, no. 2 (May 2007): 55–60. http://dx.doi.org/10.1053/j.ctsap.2007.03.004.

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Behra, Biswadeep, S. Vairamuthu, Natesan Pazhanivel, Periyasamy Jalantha, and Ganne Venkata Sudhakar Rao. "Histological and Immunohistochemical Features of Pulmonary Metastatic Oral Melanoma in a Labrador dog." Indian Journal of Veterinary Sciences & Biotechnology 18, no. 5 (November 7, 2022): 119–22. http://dx.doi.org/10.48165/ijvsbt.18.5.24.

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Melanoma is a malignant tumour that originates from melanocytes. It has been reported in human beings as well as in many domesticated animal species (Reddy et al., 1998), and wild terrestrial and marine animals. Melanomas are the most commonly diagnosed malignant tumours in the oral cavity of canines (Goldschmidt, 1985; Faramade et al., 2017). Gingiva is the most common site for canine oral malignant melanoma (OMM) but other parts like palatine, labile or buccal mucosa also act as the sites of origin (Delverdier et al., 1991). It is generally an aggressive tumour, often locally invasive, and frequently metastasizes to regional lymph nodes and lungs but metastasis to other organs like the brain, heart, spleen, and liver is not common (Goldschmidt and Hendrick, 2002). Canine OMM accounts for about 7% of all malignant tumours of canine, 11.5% to 17.1% of all oral tumours (Mikiewicz et al., 2019), and 33% to 35.8% of all malignant oral tumours (Sarowitz et al., 2017). OMM is reported in old age group animals mainly ranging from 7 to 14 years age (Esplin, 2008). Most common breeds affected by OMM include Cocker Spaniels, Golden Retrievers, Dachshunds, mixed-breed dogs (Gillard et al., 2014) but histologically well-differentiated melanocytic neoplasms (HWDMN) also reported in Golden Retrievers, Labrador, Doberman Pinscher, Irish Setters, Cocker Spaniels, Beagles, etc. (Esplin, 2008). The diagnosis of melanoma is difficult mainly in tumors without appreciable melanin. Histological appearance resembles carcinoma, lymphoma, sarcoma, and osteogenic tumours. Therefore, immunohistochemistry with numerous melanoma specific markers is mostly used for confirmatory diagnosis in human and veterinary pathology (Wick, 2008). This case report is on the occurrence of oral melanoma with pulmonary metastasis in a Labrador dog.

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Conrad, David, Alexandra Kehl, Christoph Beitzinger, Thomas Metzler, Katja Steiger, Nicole Pfarr, Konrad Fischer, Robert Klopfleisch, and Heike Aupperle-Lellbach. "Molecular Genetic Investigation of Digital Melanoma in Dogs." Veterinary Sciences 9, no. 2 (January 30, 2022): 56. http://dx.doi.org/10.3390/vetsci9020056.

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Canine digital melanoma, in contrast to canine oral melanoma, is still largely unexplored at the molecular genetic level. The aim of this study was to detect mutant genes in digital melanoma. Paraffin-embedded samples from 86 canine digital melanomas were examined for the BRAF V595E variant by digital droplet PCR (ddPCR), and for exon 11 mutations in c-kit. Furthermore, exons 2 and 3 of KRAS and NRAS were analysed by Sanger sequencing. Copy number variations (CNV) of KITLG in genomic DNA were analysed from nine dogs. The BRAF V595E variant was absent and in c-kit, a single nucleotide polymorphism was found in 16/70 tumours (23%). The number of copies of KITLG varied between 4 and 6. KRAS exon 2 codons 12 and 13 were mutated in 22/86 (25.6%) of the melanomas examined. Other mutually exclusive RAS mutations were found within the hotspot loci, i.e., KRAS exon 3 codon 61: 2/55 (3.6%); NRAS exon 2 codons 12 and 13: 2/83 (2.4%); and NRAS exon 3 codon 61: 9/86 (10.5%). However, no correlation could be established between histological malignancy criteria, survival times and the presence of RAS mutations. In summary, canine digital melanoma differs from molecular genetic data of canine oral melanoma and human melanoma, especially regarding the proportion of RAS mutations.

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Palma, Stefano Di, Ashleigh McConnell, Sara Verganti, and Mike Starkey. "Review on Canine Oral Melanoma: An Undervalued Authentic Genetic Model of Human Oral Melanoma?" Veterinary Pathology 58, no. 5 (March 9, 2021): 881–89. http://dx.doi.org/10.1177/0300985821996658.

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Oral melanoma (OM) is a highly aggressive tumor of the oral cavity in humans and dogs. Here we review the phenotypic similarities between the disease in these 2 species as the basis for the view that canine OM is a good model for the corresponding human disease. Utility of the “canine model” has likely been hindered by a paucity of information about the extent of the molecular genetic similarities between human and canine OMs. Current knowledge of the somatic alterations that underpin human tumorigenesis and metastatic progression is relatively limited, primarily due to the rarity of the disease in humans and consequent lack of opportunity for large-scale molecular analysis. The molecular genetic comparisons between human and canine OMs that have been completed indicate some overlap between the somatic mutation profiles of canine OMs and a subset of human OMs. However, further comparative studies featuring, in particular, larger numbers of human OMs are required to provide substantive evidence that canine OMs share mechanisms of tumorigenesis with at least a subset of human OMs. Future molecular genetic investigations of both human and canine OMs should investigate how primary tumors develop a metastatic gene expression signature and the genetic and epigenetic alterations specific to metastatic sites. Such studies may identify genetic alterations and pathways specific to the metastatic disease which could be targetable by new drugs.

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Shimoyama, Y., Y. Akihara, D. Kirat, H. Iwano, K. Hirayama, Y. Kagawa, T. Ohmachi, et al. "Expression of Monocarboxylate Transporter 1 in Oral and Ocular Canine Melanocytic Tumors." Veterinary Pathology 44, no. 4 (July 2007): 449–57. http://dx.doi.org/10.1354/vp.44-4-449.

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Solid tumors are composed of a heterogeneous population of cells surviving in various concentrations of oxygen. In a hypoxic environment, tumor cells generally up-regulate glycolysis and, therefore, generate more lactate that must be expelled from the cell through proton transporters to prevent intracellular acidosis. Monocarboxylate transporter 1 (MCT1) is a major proton transporter in mammalian cells that transports monocarboxylates, such as lactate and pyruvate, together with a proton across the plasma membrane. Melanocytic neoplasia occurs frequently in dogs, but the prognosis is highly site-dependent. In this study, 50 oral canine melanomas, which were subdivided into 3 histologic subtypes, and 17 ocular canine melanocytic neoplasms (14 melanocytomas and 3 melanomas) were used to examine and compare MCT1 expression. Immunohistochemistry using a polyclonal chicken anti-rat MCT1 antibody showed that most oral melanoma exhibited cell membrane staining, although there were no significant differences observed among the 3 histologic subtypes. In contrast, the majority of ocular melanocytic tumors were not immunoreactive. Additionally, we documented the presence of a 45-kDa band in cell membrane protein Western blots, and sequencing of a reverse transcriptase polymerase chain reaction band of expected size confirmed its identity as a partial canine MCT1 transcript in 3 oral tumors. Increased MCT1 expression in oral melanomas compared with ocular melanocytic tumors may reflect the very different biology between these tumors in dogs. These results are the first to document canine MCT1 expression in canine tumors and suggest that increased MCT1 expression may provide a potential therapeutic target for oral melanoma.

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Prouteau and André. "Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison." Genes 10, no. 7 (June 30, 2019): 501. http://dx.doi.org/10.3390/genes10070501.

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Despite recent genetic advances and numerous ongoing therapeutic trials, malignant melanoma remains fatal, and prognostic factors as well as more efficient treatments are needed. The development of such research strongly depends on the availability of appropriate models recapitulating all the features of human melanoma. The concept of comparative oncology, with the use of spontaneous canine models has recently acquired a unique value as a translational model. Canine malignant melanomas are naturally occurring cancers presenting striking homologies with human melanomas. As for many other cancers, dogs present surprising breed predispositions and higher frequency of certain subtypes per breed. Oral melanomas, which are much more frequent and highly severe in dogs and cutaneous melanomas with severe digital forms or uveal subtypes are subtypes presenting relevant homologies with their human counterparts, thus constituting close models for these human melanoma subtypes. This review addresses how canine and human melanoma subtypes compare based on their epidemiological, clinical, histological, and genetic characteristics, and how comparative oncology approaches can provide insights into rare and poorly characterized melanoma subtypes in humans that are frequent and breed-specific in dogs. We propose canine malignant melanomas as models for rare non-UV-induced human melanomas, especially mucosal melanomas. Naturally affected dogs offer the opportunity to decipher the genetics at both germline and somatic levels and to explore therapeutic options, with the dog entering preclinical trials as human patients, benefiting both dogs and humans.

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De Andrade, Gisele Braziliano, Alanderson Rodrigues Da Silva, João Bosco Vilela Campos, Joyce Katiuccia Medeiros Ramos Carvalho, Rosalina Marina Infiesta Zulim, Luciano Pereira De Barros, Cristiano Marcelo Espinola Carvalho, and Heitor Miraglia Herreira. "Canine Oral Osteocartilaginous Malignant Amelanotic Melanoma with Pulmonary Metastasis." Acta Scientiae Veterinariae 46 (July 29, 2018): 8. http://dx.doi.org/10.22456/1679-9216.87456.

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Background: Melanomas are typically malignant neoplasms commonly observed in the oral cavity of dogs. The classical presentation of melanomas with characteristic melanin pigmentation is easy to diagnose; however, in some cases, the lack of melanin production in the amelanotic oral tumors cause a delay in establishing the precocious diagnosis and consequent treatment. The aim of this report was to evaluate the histopathological and immunohistochemical aspects of an oral amelanotic melanoma with osteocartilaginous formation and metastasis in a dog, in a temporal way.Case: A 10-year-old male German Shepherd dog, presenting mouth bleeding with an amelanotic melanoma located between the upper incisors was received at the Veterinary Hospital of the Catholic University Dom Bosco (UCDB), Campo Grande, MS, Brazil. The animal was clinically evaluated and radiography was performed. The tumor was surgically removed and a sample was collected for histopathological examination that revealed spindloid and some epithelioid morphological cell types surrounded by a fibromatous matrix with moderate amounts of fibrovascular stroma. Approximately 1 month after surgical removal, recovery of the tumor was observed, and a second clinical analysis and collection of sample were performed. These procedures were repeated three times showing the same histopathological characteristics added by myxoid, chondroid, fibromatous tissue, and small groups of chondrocytes as well as central areas of irregular mineralized spicules. X-ray examination revealed proliferative and lytic bone infiltration in the jaw. Immunohistochemical analysis for melanocytic differentiation markers was performed showing positivity to Melan-A, tyrosinase and HMB-45 immunoreactivity, while no S100 reactivity was detected. After 11 months of the first biopsy, pleural effusion and radiopaque disseminated nodules of 1cm in the lungs were detected by X-ray. The animal died and necropsy was conducted. Multiple masses were observed in the lung and at the parietal pleura, suggesting lung metastasis by the positivity for Melan-A.Discussion: The dog was first diagnosed with fibromatous epulis based on the observation of fibroblastic tissue and spindle cells with intense vascularization associated to the site of the tumor and its macroscopic aspect. In the subsequent follow-ups the tumor displayed malignant characteristics observed by recurrence after each surgery, as the tumor returned even larger, aggressive, and infiltrative. From the second biopsy, the histopathological analysis showed the undifferentiated character of epithelioid neoplastic cells, demonstrated by the increase of cartilage and osteoid tissue and the mineral deposit. The phenomenon of the tumor stroma to form cartilage and bone is highlighted here because myxoid change and cartilage formation were frequently observed at the site where amelanotic spindle cells were actively proliferating. It is possible that neoplastic melanocytic cells themselves were involved in the development of the osteocartilaginous areas. Although no cytoplasmic melanin pigmentation was found in the tumor fragments, specific melanocytic markers for melanoma detected neoplastic melanocytes and unmelanized melanosomes. The positive reaction for Melan-A, HMB-45, and tyrosinase in the epithelioid, spindle, and cartilaginous cell groups of the neoplasia indicated amelanotic melanoma with osteocartilaginous differentiation. The negative HMB-45, S100, and tyrosinase expression in lung metastasis may be due to the fact that melanomas express aberrant markers and are also known to display occasional loss of their classic immunophenotype. Amelanotic melanoma can be underdiagnosed due to rapid progression of the tumor allied to the dedifferentiation ability of melanocytes. Thus, the follow up study of cell morphology and immunohistochemical analysis for melanogenic factors can be important determinants in diagnosis.

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Tellado, Matías Nicolás, Felipe Horacio Maglietti, Sebastián Diego Michinski, Guillermo Ricardo Marshall, and Emanuela Signori. "Electrochemotherapy in treatment of canine oral malignant melanoma and factors influencing treatment outcome." Radiology and Oncology 54, no. 1 (March 7, 2020): 68–78. http://dx.doi.org/10.2478/raon-2020-0014.

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AbstractBackgroundOral malignant melanoma is the most common, but aggressive oral cancer in dogs with poor prognosis. Electrochemotherapy (ECT) has therapeutic potential in such tumors as effective local treatment. Therefore, the aim of this prospective clinical study was to evaluate treatment effectiveness of ECT in as first line treatment for canine oral malignant melanoma, and search for factors influencing treatment outcome.MethodsSixty-seven canines with primary oral malignant melanoma, non-candidates for first-line therapy, were enrolled. All dogs received ECT and follow-up exams for the span of two years.ResultsBased on RECIST criteria, the objective response rate was 100%, 89.5%, 57.7%, and 36.4%, in stage I, II, III and IV, respectively. Only patients in stage I, II and III with partial or complete response improved their quality of life. The median time to progression was 11, 7, 4 and 4 months, and median survival time after the treatment was 16.5, 9.0, 7.5 and 4.5 months, for patients in stage I, II, III and IV, respectively. Significantly better was local response in stage I and II disease (p = 0.0013), without the bone involvement (p = 0.043)ConclusionsElectrochemotherapy is effective local treatment of oral canine malignant melanoma when no alternative treatment is available. Better response is expected in stage I and II patients with tumors without bone involvement.

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Almela, Ramón, and Agustina Ansón. "A Review of Immunotherapeutic Strategies in Canine Malignant Melanoma." Veterinary Sciences 6, no. 1 (February 12, 2019): 15. http://dx.doi.org/10.3390/vetsci6010015.

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In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. Classical clinical management remains challenging; thus, novel and more efficacious treatment strategies are needed. Evidence-based medicine supports the role of the immune system to treat neoplastic diseases. Besides, immunotherapy offers the possibility of a precise medicinal approach to treat cancer. In recent years, multiple immunotherapeutic strategies have been developed, and are now recognized as a pillar of treatment. In addition, dogs represent a good model for translational medicine purposes. This review will cover the most relevant immunotherapeutic strategies for the treatment of canine malignant melanoma, divided among five different categories, namely, monoclonal antibodies, nonspecific immunotherapy activated by bacteria, vaccines, gene therapy, and lymphokine-activated killer cell therapy.

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Zamarian, Valentina, Carlotta Catozzi, Lorenzo Ressel, Riccardo Finotello, Fabrizio Ceciliani, Miguel Vilafranca, Jaume Altimira, and Cristina Lecchi. "MicroRNA Expression in Formalin-Fixed, Paraffin-Embedded Samples of Canine Cutaneous and Oral Melanoma by RT-qPCR." Veterinary Pathology 56, no. 6 (September 16, 2019): 848–55. http://dx.doi.org/10.1177/0300985819868646.

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MicroRNAs (miRNAs) are a class of small, noncoding RNA that post-transcriptionally regulate protein expression. miRNAs are emerging as clinical biomarkers of many diseases, including tumors. The aim of this study was to investigate whether miRNA expression could vary in melanoma samples derived from formalin-fixed, paraffin-embedded (FFPE) tissues. The study included 4 groups: (1) 9 samples of oral canine malignant melanoma, (2) 10 samples of cutaneous malignant melanoma, (3) 5 samples of healthy oral mucosa, and (4) 7 samples of healthy skin. The expression levels of 6 miRNAs—miR-145, miR-146a, miR-425-5p, miR-223, miR-365, and miR-134—were detected and assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) using TaqMan probes. Cutaneous canine malignant melanoma showed a decrease of the expression level of miR-145 and miR-365 and an increase of miR-146a and miR-425-5p compared to control samples. MiR-145 was also downregulated in oral canine malignant melanoma. The miRNAs with decreased expression may regulate genes involved in RAS, Rap1, and transforming growth factor β (TGF-β) signaling pathways, as well as upregulated genes associated with phosphatidylinositol signaling system, adherens junction, and RAS signaling pathways. In conclusion, miR-145, miR-365, miR-146a, and miR-425-5p were differentially expressed in canine malignant melanoma and healthy FFPE samples, suggesting that they may play a role in canine malignant melanoma pathogenesis.

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Smedley, Rebecca C., Tuddow Thaiwong, Lorna E. Deeth, and Matti Kiupel. "Correlation Between KIT Expression and c-Kit Mutations in 2 Subtypes of Canine Oral Melanocytic Neoplasms." Veterinary Pathology 58, no. 4 (April 29, 2021): 683–91. http://dx.doi.org/10.1177/03009858211009784.

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c-Kit mutations have been reported in 15% to 40% of certain human melanoma subtypes, including those histologically similar to canine oral malignant melanomas. Therapeutic response to tyrosine kinase inhibitors has been demonstrated in those human patients. As canine oral malignant melanomas tend to have a poor prognosis despite aggressive surgical removal, evaluation of KIT expression and identification of c-Kit mutations in canine oral melanocytic neoplasms was performed to determine if there is any indication that tyrosine kinase inhibitor drugs might effectively treat any of these cases. This study evaluated 27 canine oral malignant melanomas and 12 canine histologically well-differentiated oral melanocytic neoplasms for activating c-Kit mutations, determined differences in immunohistochemical expression of KIT and c-Kit mutation status, and determined if KIT expression could predict c-Kit mutation status. Among samples that contained intraepithelial nests of neoplastic melanocytes in the KIT-labeled sections, KIT was expressed within cells in these nests in 22/23 (96%) malignant melanomas and 5/7 histologically well-differentiated neoplasms. KIT was expressed in 10% to 30% of neoplastic melanocytes in the lamina propria in 3/24 (13%) malignant melanomas, but 0/9 (0%) histologically well-differentiated neoplasms. Next-generation sequencing identified 85 variants in c-Kit, including 9 nonsynonymous mutations that resulted in amino acid changes predicted to affect protein function. c-Kit mutations with predicted deleterious protein effects were more common in malignant melanomas (8/27 [30%] vs 1/12 [8%]). There was no apparent relationship between detected c-Kit mutations and KIT expression. These results do not support the use of therapies that target c-Kit.

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Rahman, Md Mahfuzur, Yu-Chang Lai, Al Asmaul Husna, Hui-wen Chen, Yuiko Tanaka, Hiroaki Kawaguchi, Noriaki Miyoshi, Takayuki Nakagawa, Ryuji Fukushima, and Naoki Miura. "Micro RNA Transcriptome Profile in Canine Oral Melanoma." International Journal of Molecular Sciences 20, no. 19 (September 28, 2019): 4832. http://dx.doi.org/10.3390/ijms20194832.

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MicroRNAs (miRNAs) dysregulation contribute the cancer pathogenesis. However, the miRNA profile of canine oral melanoma (COM), one of the frequent malignant melanoma in dogs is still unrevealed. The aim of this study is to reveal the miRNA profile in canine oral melanoma. MiRNAs profile of oral tissues from normal healthy dogs and COM patients were compared by next-generation sequencing. Along with tumour suppressor miRNAs, we report 30 oncogenic miRNAs in COM. The expressions of miRNAs were further confirmed by quantitative real-time PCR (qPCR). Pathway analysis showed that deregulated miRNAs impact on cancer and signalling pathways. Three oncogenic miRNAs targets (miR-450b, 301a, and 223) from human study also were down-regulated in COM and had a significant negative correlation with their respective miRNA. Furthermore, we found that miR-450b expression is higher in metastatic cells and regulated MMP9 expression through a PAX9-BMP4-MMP9 axis. In silico analysis indicated that miR-126, miR-20b, and miR-106a regulated the highest numbers of differentially expressed transcription factors with respect to human melanoma. Chromosomal enrichment analysis revealed the X chromosome was enriched with oncogenic miRNAs. We comprehensively analyzed the miRNA’s profile in COM which will be a useful resource for developing therapeutic interventions in both species.

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Pellin, MacKenzie A. "The Use of Oncept Melanoma Vaccine in Veterinary Patients: A Review of the Literature." Veterinary Sciences 9, no. 11 (October 28, 2022): 597. http://dx.doi.org/10.3390/vetsci9110597.

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The Oncept melanoma vaccine is xenogeneic DNA vaccine targeting tyrosinase. It is USDA approved for treatment of stage II to III canine oral melanoma and is also used off-label for melanomas arising in other locations and in other species. While the vaccine appears safe, the published data is mixed as to whether it provides a survival benefit, and the use of the vaccine is somewhat controversial in the veterinary oncology community. In this paper, the published literature describing the use of Oncept is reviewed and evaluated.

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Porcellato, Ilaria, Chiara Brachelente, Livia De Paolis, Laura Menchetti, Serenella Silvestri, Monica Sforna, Gaia Vichi, Selina Iussich, and Luca Mechelli. "FoxP3 and IDO in Canine Melanocytic Tumors." Veterinary Pathology 56, no. 2 (October 31, 2018): 189–99. http://dx.doi.org/10.1177/0300985818808530.

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Human melanoma is one of the deadliest forms of cancer, with poor prognosis and high resistance to chemotherapy and radiotherapy. The discovery of immunosuppressive mechanisms in the human melanoma microenvironment led to the use of new prognostic markers and to the development of immunotherapies targeting immune checkpoint molecules. Immunoescape mechanisms in canine melanoma have not yet been investigated, and no such immunotherapy has been tested. The aim of this study was to provide preliminary data on the expression of transcription factor forkhead box protein P3 (FoxP3) and indoleamine 2,3-dioxygenase (IDO) in primary canine melanocytic tumors and to investigate their prognostic role. Formalin-fixed, paraffin-embedded samples from 74 canine melanocytic tumors (26 oral melanomas, 23 cutaneous melanomas, and 25 cutaneous melanocytomas) were retrospectively evaluated by immunohistochemistry to explore the expression of FoxP3 and IDO. An increased risk of death due to melanoma was associated with a higher number of FoxP3+ cells per high-power field (FoxP3+/HPF), a higher percentage of CD3+ cells that were also FoxP3+ infiltrating and surrounding the tumor (%FoxP3), and a higher number of IDO+ cells/HPF (IDO+/HPF). A prognostic value for FoxP3 and IDO is suggested by our study, with optimal cutoffs of 14.7 FoxP3+ cells/HPF, 6.1 IDO+ cells/HPF, and 12.5% FoxP3+ cells. Both markers were also associated with tumor type. Multivariable analysis identified IDO+/HPF ( P < .001) as an independent prognostic marker. Even though stratification by diagnosis caused a loss of significance, results from the present study suggest a prognostic role for IDO and FoxP3, possibly related to the establishment of an immunosuppressive microenvironment.

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Sforna, Monica, Elisabetta Chiaradia, Ilaria Porcellato, Serenella Silvestri, Giulia Moretti, Luca Mechelli, and Chiara Brachelente. "Characterization of Primary Cultures of Normal and Neoplastic Canine Melanocytes." Animals 11, no. 3 (March 10, 2021): 768. http://dx.doi.org/10.3390/ani11030768.

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Although numerous animal models, especially mouse models, have been established for the study of melanoma, they often fail to accurately describe the mechanisms of human disease because of their anatomic, physiological, and immune differences. The dog, as a spontaneous model of melanoma, is nowadays considered one of the most valid alternatives due to the heterogeneity of clinical presentations and of histological and genetic similarities of canine melanoma with the human counterpart. The aim of the study was to optimize a protocol for the isolation and cultivation of healthy and neoplastic canine melanocytes derived from the same animal and obtained from cutaneous and mucosal (oral) sites. We obtained five primary tumor cell cultures (from 2 cutaneous melanoma, 2 mucosal melanoma and 1 lymph node metastasis) and primary normal melanocyte cell cultures (from normal skin and mucosa) from the same dogs. Immunocytochemical characterization with Melan A, PNL2 and S100 antibodies confirmed the melanocytic origin of the cells. This work contributes to expanding the case record of studies on canine melanoma cell cultures as suitable model to study human and canine melanoma. To the authors’ knowledge, this is the first report of isolation of normal skin and mucosal canine melanocytes.

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Brocca, Ginevra, Beatrice Poncina, Alessandro Sammarco, Laura Cavicchioli, and Massimo Castagnaro. "KIT Somatic Mutations and Immunohistochemical Expression in Canine Oral Melanoma." Animals 10, no. 12 (December 10, 2020): 2370. http://dx.doi.org/10.3390/ani10122370.

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Canine oral melanoma (COM) is an aggressive neoplasm with a low response to therapies, sharing similarities with human mucosal melanomas. In the latter, significant alterations of the proto-oncogene KIT have been shown, while in COMs only its exon 11 has been adequately investigated. In this study, 14 formalin-fixed, paraffin-embedded COMs were selected considering the following inclusion criteria: unequivocal diagnosis, presence of healthy tissue, and a known amplification status of the gene KIT (seven samples affected and seven non-affected by amplification). The DNA was extracted and KIT target exons 13, 17, and 18 were amplified by PCR and sequenced. Immunohistochemistry (IHC) for KIT and Ki67 was performed, and a quantitative index was calculated for each protein. PCR amplification and sequencing was successful in 97.62% of cases, and no single nucleotide polymorphism (SNP) was detected in any of the exons examined, similarly to exon 11 in other studies. The immunolabeling of KIT was positive in 84.6% of the samples with a mean value of 3.1 cells in positive cases, yet there was no correlation with aberration status. Our findings confirm the hypothesis that SNPs are not a frequent event in KIT activation in COMs, with the pathway activation relying mainly on amplification.

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Yasumaru, Cassia C., José Guilherme Xavier, Ricardo De Francisco Strefezzi, and Cristina O. Massoco Salles-Gomes. "Intratumoral T-Lymphocyte Subsets in Canine Oral Melanoma and Their Association With Clinical and Histopathological Parameters." Veterinary Pathology 58, no. 3 (March 25, 2021): 491–502. http://dx.doi.org/10.1177/0300985821999321.

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Canine oral melanoma is a common, aggressive tumor with limited treatment options. Tumor-infiltrating lymphocytes (TILs) are important in antitumor immunity. This study used histopathology and immunophenotyping by flow cytometry to evaluate the presence and distribution of TILs in canine oral melanoma, including the frequency of CD8+ T cells, CD4+ T cells, and regulatory T cells. Fifty samples of oral melanoma from 45 dogs that did not receive treatment prior to surgery were included in the study. The distribution of TILs in the tissue (brisk, nonbrisk, and absent) was evaluated in 48 samples. Twenty-eight (58%) samples had a brisk distribution pattern, 10 (21%) samples had a nonbrisk pattern, and 10 (21%) samples had an absent TIL pattern. Comparing the histological evaluation and the immunophenotyping data, it was observed that samples with a brisk TIL pattern had a higher frequency of CD8+ T lymphocytes ( P = .05) and a lower frequency of CD4+/CD25+/FoxP3+ Tregs ( P = .03), compared to the samples with nonbrisk and absent infiltrate patterns. Patients with a higher survival rate had higher TIL scores ( P = .002), a brisk or nonbrisk TIL pattern ( P = .001), and an increased frequency of CD8+ T lymphocytes infiltrating the tumor ( P = .003). Our analysis suggests that the evaluation of TILs in canine oral melanoma is relevant to predict tumor aggressiveness and patient prognosis.

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YOKOE, INORU, KAZUO AZUMA, KEISHI HATA, TOSHIYUKI MUKAIYAMA, TAKAHIRO GOTO, TAKESHI TSUKA, TOMOHIRO IMAGAWA, et al. "Clinical systemic lupeol administration for canine oral malignant melanoma." Molecular and Clinical Oncology 3, no. 1 (October 30, 2014): 89–92. http://dx.doi.org/10.3892/mco.2014.450.

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Hitte, Christophe, Céline Le Béguec, Edouard Cadieu, Valentin Wucher, Aline Primot, Anaïs Prouteau, Nadine Botherel, et al. "Genome-Wide Analysis of Long Non-Coding RNA Profiles in Canine Oral Melanomas." Genes 10, no. 6 (June 23, 2019): 477. http://dx.doi.org/10.3390/genes10060477.

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Mucosal melanomas (MM) are rare aggressive cancers in humans, and one of the most common forms of oral cancers in dogs. Similar biological and histological features are shared between MM in both species, making dogs a powerful model for comparative oncology studies of melanomas. Although exome sequencing recently identified recurrent coding mutations in canine MM, little is known about changes in non-coding gene expression, and more particularly, in canine long non-coding RNAs (lncRNAs), which are commonly dysregulated in human cancers. Here, we sampled a large cohort (n = 52) of canine normal/tumor oral MM from three predisposed breeds (poodles, Labrador retrievers, and golden retrievers), and used deep transcriptome sequencing to identify more than 400 differentially expressed (DE) lncRNAs. We further prioritized candidate lncRNAs by comparative genomic analysis to pinpoint 26 dog–human conserved DE lncRNAs, including SOX21-AS, ZEB2-AS, and CASC15 lncRNAs. Using unsupervised co-expression network analysis with coding genes, we inferred the potential functions of the DE lncRNAs, suggesting associations with cancer-related genes, cell cycle, and carbohydrate metabolism Gene Ontology (GO) terms. Finally, we exploited our multi-breed design to identify DE lncRNAs within breeds. This study provides a unique transcriptomic resource for studying oral melanoma in dogs, and highlights lncRNAs that may potentially be diagnostic or therapeutic targets for human and veterinary medicine.

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Igna, Cornel, Daniel Bumb, Bogdan Sicoe, Roxana Dascalu, and Larisa Schuszler. "TREATMENT OF DOGS WITH ORAL MELANOMA RECURRENCE BY DIODE LASER EXCISION." Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Veterinary Medicine 73, no. 2 (November 29, 2016): 265. http://dx.doi.org/10.15835/buasvmcn-vm:12072.

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Introduction: Treatment of oral melanomas utilizes the surgical excision-resection (Culp et al., 2013) and/or radiation therapy (Proulx et al., 2003), chemotherapy with carboplatin (Brockley et al., 2013), immunotherapy (Ottnod et al., 2013). Treatment based on surgical excision is usually palliative (Freeman et al., 2003). Aims: In the literature even though there are data concerning the prognosis of oral melanomas in dogs after surgery, are missing data after laser excision. Taking into account these findings we wished to present our experience regarding three cases of oral melanoma recurrence and immediate and long term laser surgery results. Materials and Methods: The casuistry consisted of three dogs with recurrent oral malignant melanomas, subjected to surgical reintervention. The initial diagnosis was melanotic melanoma in stage I or II. The animals were brought back at different time intervals from originally excision with electric scalpel. Before reintervention, dogs were subjected to clinical, paraclinical exam and biopsy. Excision of the tumor mass was made with an optical fiber hawing a diameter of 400µm, at a power of 10W and a wavelength of 940 nm with a diode laser. At 1, 2, 3, 6 and 12 months after laser reintervention the dogs were reexamined. Results: Average time in which appeared canine oral melanoma relapse was 58.6 days. After reexamination all cases where reinstatement in stage I. Operators times were held in conditions of comfort with wide access, minimum bleeding, effective hemostasis. After surgery at 24 hours on the intervention place a slight local redness, without swelling and bleeding was observed. Palpation revealed initially also a slight local sensitivity which completely disappeared in 48 hours. There were no grasping and chewing disturbances. Macroscopic healing occurred in 7-9 days. At last recheck performed at 12 months there were no evidences of tumour recurrence or metastasis. Conclusion: Diode laser excision of oral malignant melanoma in dogs can be an alternative palliative procedure to invasive surgical resection procedures. The average of free recurrence and metastasis time after laser surgery has exceeded 360 days in these three cases.

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Verganti, S., D. Berlato, L. Blackwood, I. Amores-Fuster, G. A. Polton, R. Elders, R. Doyle, A. Taylor, and S. Murphy. "Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK." Journal of Small Animal Practice 58, no. 1 (January 2017): 10–16. http://dx.doi.org/10.1111/jsap.12613.

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Bergin, I. L., R. C. Smedley, D. G. Esplin, W. L. Spangler, and M. Kiupel. "Prognostic Evaluation of Ki67 Threshold Value in Canine Oral Melanoma." Veterinary Pathology 48, no. 1 (December 2010): 41–53. http://dx.doi.org/10.1177/0300985810388947.

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Medven Zagradišnik, L., M. Hohšteter, I. C. Šoštarić-Zuckermann, A. Gudan Kurilj, D. Grabarević, B. Artuković, and Ž. Grabarević. "Immunohistochemical Evaluation of Cell Progression Markers in Canine Oral Melanoma." Journal of Comparative Pathology 156, no. 1 (January 2017): 124. http://dx.doi.org/10.1016/j.jcpa.2016.11.213.

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Putnová, Barbora, Jana Burová, Marilena Georgiou, Tomáš Fichtel, Ladislav Stehlík, Lucia Frgelecová, and Miša Škorič. "Occurrence site of canine oral lesions: a retrospective study of 659 cases." Acta Veterinaria Brno 89, no. 2 (2020): 179–87. http://dx.doi.org/10.2754/avb202089020179.

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Many types of tumorous and tumour-like lesions occur in the oral cavity of dogs. Even benign neoplasia often represents great inconvenience due to potential restrictions of therapeutic surgical approach in this area. Whereas in human medicine, there are statistical data describing areas of the oral cavity, that are more prevalent for development of particular neoplasia, in veterinary medicine, these data are not yet available. The aim of this study was to evaluate the prevalence of tumours in dogs with oral neoplasia, the occurrence site of the most common neoplastic lesions in the canine oral cavity, as well as the effect of age and sex on the prevalence of these lesions. In this study we investigated oral tumorous lesions from 659 dogs, out of which 352 lesions were diagnosed as tumours and 307 as tumour-like lesions. The most common tumours encountered were melanoma (42%, n = 148), squamous cell carcinoma (16%, n = 57) and canine acanthomatous ameloblastoma (10%, n = 35). The median age of dogs with oral neoplasia was 9.9 years, with the range of 0.2 to 17.5 years. There was no significant association between sex and the type of oral lesion (tumorous and tumour-like). Melanoma was most commonly present in the caudal maxillary region, squamous cell carcinoma on the mouth floor, canine acanthomatous ameloblastoma in the area of the rostral mandible, plasmacytoma on the tongue, osteosarcoma was most often diagnosed in the caudal parts of oral cavity and fibrosarcoma did not have a specific site of occurrence.

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Sato, Toshihiko, Miki Sakonju, and Hiroyuki Nanba. "A Case of Canine Oral Melanoma with Similar Histopathological Findings to Human Desmoplastic Melanoma." Journal of Japan Veterinary Cancer Society 5, no. 1 (2014): 1–5. http://dx.doi.org/10.12951/jvcs.2013-002.

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Hardwick, Laura. "A Comparative View on Molecular Alterations and Potential Therapeutic Strategies for Canine Oral Melanoma." Veterinary Sciences 8, no. 11 (November 22, 2021): 286. http://dx.doi.org/10.3390/vetsci8110286.

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Canine oral melanoma (COM) is a highly aggressive tumour associated with poor prognosis due to metastasis and resistance to conventional anti-cancer therapies. As with human mucosal melanoma, the mutational landscape is predominated by copy number aberrations and chromosomal structural variants, but differences in study cohorts and/or tumour heterogeneity can lead to discordant results regarding the nature of specific genes affected. This review discusses somatic molecular alterations in COM that result from single nucleotide variations, copy number changes, chromosomal rearrangements, and/or dysregulation of small non-coding RNAs. A cross-species comparison highlights notable recurrent aberrations, and functionally grouping dysregulated proteins reveals unifying biological pathways that may be critical for oncogenesis and metastasis. Finally, potential therapeutic strategies are considered to target these pathways in canine patients, and the benefits of collaboration between science, medical, and veterinary communities are emphasised.

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Sarbu, Luminita, Barbara E. Kitchell, and Philip J. Bergman. "Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma – a retrospective study." Journal of Feline Medicine and Surgery 19, no. 2 (July 10, 2016): 224–30. http://dx.doi.org/10.1177/1098612x15623319.

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Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group’s common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

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Noguchi, Shunsuke, Kohei Yagi, Nanako Okamoto, Yusuke Wada, and Toshiyuki Tanaka. "Prognostic Factors for the Efficiency of Radiation Therapy in Dogs with Oral Melanoma: A Pilot Study of Hypoxia in Intraosseous Lesions." Veterinary Sciences 10, no. 1 (December 22, 2022): 4. http://dx.doi.org/10.3390/vetsci10010004.

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Unresectable oral melanoma is often treated with radiation therapy (RT) and may show a temporary response to therapy. The clinical stage is one of the well-known prognostic factors for canine oral melanoma. However, the factors that directly affect the response to RT have remained unclear. This study aimed to validate the risk factors for recurrence after RT. Sixty-eight dogs with oral melanomas were included in this study. All dogs were treated with palliative RT using a linear accelerator without adjuvant therapies. After RT, the time to local recurrence (TTR) and overall survival (OS) were evaluated using the log-rank test. As a result, clinical stage and response to therapy were the significant independent prognostic factors in the multivariate analysis. The presence of local bone lysis and non-combination with cytoreductive surgery were associated with a worse response to RT. Immunohistochemical analysis for hypoxia-inducible factor-1α indicated that tumor cells invading the bone are under hypoxic conditions, which may explain a poorer efficiency of RT in dogs with bone lysis. In conclusion, clinical stage and combination with debulking surgery were needed to improve the efficiency of RT.

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Nordio, Laura, Andreia T. Marques, Cristina Lecchi, Alberto M. Luciano, Damiano Stefanello, and Chiara Giudice. "Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas." Journal of Histochemistry & Cytochemistry 66, no. 8 (April 2, 2018): 585–93. http://dx.doi.org/10.1369/0022155418766292.

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Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

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Giuliano, Antonio. "Companion Animal Model in Translational Oncology; Feline Oral Squamous Cell Carcinoma and Canine Oral Melanoma." Biology 11, no. 1 (December 31, 2021): 54. http://dx.doi.org/10.3390/biology11010054.

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Companion animals with naturally occurring cancers can provide an advantageous model for cancer research and in particular anticancer drug development. Compared to commonly utilized mouse models, companion animals, specifically dogs and cats, share a closer phylogenetical distance, body size, and genome organization. Most importantly, pets develop spontaneous, rather than artificially induced, cancers. The incidence of cancer in people and companion animals is quite similar and cancer is the leading cause of death in dogs over 10 years of age. Many cancer types in dogs and cats have similar pathological, molecular, and clinical features to their human counterparts. Drug toxicity and response to anti-cancer treatment in dogs and cats are also similar to those in people. Companion animals share their lives with their owners, including the environmental and socioeconomic cancer-risk factors. In contrast to humans, pets have a shorter life span and cancer progression is often more rapid. Clinical trials in companion animals are cheaper and less time consuming compared to human trials. Dogs and cats with naturally occurring cancers are an ideal and unique model for human cancer research. Model selection for the specific type of cancer is of pivotal importance. Although companion animal models for translational research have been reviewed previously, this review will try to summarize the most important advantages and disadvantages of this model. Feline oral squamous cell carcinoma as a model for head and neck squamous cell carcinoma and canine oral melanoma as a model for mucosal melanoma and immunotherapy in people will be discussed as examples.

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Ploypetch, Sekkarin, Sittiruk Roytrakul, Janthima Jaresitthikunchai, Narumon Phaonakrop, Patharakrit Teewasutrakul, Anudep Rungsipipat, and Gunnaporn Suriyaphol. "Salivary proteomics in monitoring the therapeutic response of canine oral melanoma." PLOS ONE 16, no. 8 (August 19, 2021): e0256167. http://dx.doi.org/10.1371/journal.pone.0256167.

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Saliva biomarkers are suitable for monitoring the therapeutic response of canine oral melanoma (COM), because saliva directly contacts the tumor, and saliva collection is non-invasive, convenient and cost effective. The present study aimed to investigate novel biomarkers from the salivary proteome of COM treated with surgery and a chemotherapy drug, carboplatin, 1–6 times, using a liquid chromatography–tandem mass spectrometry approach. The expression of a potential salivary biomarker, ubiquitin D (UBD), was observed and verified by western blot analysis. A significantly increased ratio of free UBD (fUBD) to conjugated UBD (cUBD) was shown in the pre-surgery stage (PreS) in OM dogs with short-term survival (STS) (less than 12 months after surgery) compared with that with long-term survival (more than 12 months after surgery). In dogs with STS, the ratio was also shown to be augmented in PreS compared with that after surgery, followed by treatment with carboplatin twice, 4 and 5 times [After treatment (AT)2, AT4 and AT5]. In addition, the expression of fUBD was enhanced in PreS compared with that of AT2 in the STS group. In conclusion, this study revealed that a ratio of fUBD to cUBD in PreS was plausibly shown to be a potential prognostic biomarker for survival in dogs with OM.

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MacEwen, E. Gregory, A. K. Patnaik, H. J. Harvey, A. A. Hayes, and R. Matus. "Canine Oral Melanoma: Comparison of Surgery Versus Surgery Plus Corynebacterium parvum." Cancer Investigation 4, no. 5 (January 1986): 397–402. http://dx.doi.org/10.3109/07357908609017520.

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Taylor, K. H., A. N. Smith, M. Higginbotham, D. D. Schwartz, D. M. Carpenter, and E. M. Whitley. "Expression of vascular endothelial growth factor in canine oral malignant melanoma." Veterinary and Comparative Oncology 5, no. 4 (December 2007): 208–18. http://dx.doi.org/10.1111/j.1476-5829.2007.00130.x.

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Zamboni, Clarissa, Ginevra Brocca, Serena Ferraresso, Silvia Ferro, Alessandro Sammarco, Chiara Dal Corso, Selina Iussich, et al. "Cyclin D1 immunohistochemical expression and somatic mutations in canine oral melanoma." Veterinary and Comparative Oncology 18, no. 2 (October 9, 2019): 231–38. http://dx.doi.org/10.1111/vco.12539.

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Hoopes, P. Jack, Robert J. Wagner, Kayla Duval, Kevin Kang, David J. Gladstone, Karen L. Moodie, Margaret Crary-Burney, et al. "Treatment of Canine Oral Melanoma with Nanotechnology-Based Immunotherapy and Radiation." Molecular Pharmaceutics 15, no. 9 (April 3, 2018): 3717–22. http://dx.doi.org/10.1021/acs.molpharmaceut.8b00126.

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Hahn, K. A., D. B. DeNicola, R. C. Richardson, and E. A. Hahn. "Canine oral malignant melanoma: Prognostic utility of an alternative staging system." Journal of Small Animal Practice 35, no. 5 (May 1994): 251–56. http://dx.doi.org/10.1111/j.1748-5827.1994.tb03273.x.

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Nordio, L., F. Genova, V. Serra, C. Bazzocchi, M. L. Longeri, D. Stefanello, M. Rondena, and C. Giudice. "LTA4H and FXR1 Gene and Protein Expression in Canine Oral Melanoma." Journal of Comparative Pathology 158 (January 2018): 122. http://dx.doi.org/10.1016/j.jcpa.2017.10.084.

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Pazzi, Paolo, Gerhard Steenkamp, and Anouska J. Rixon. "Treatment of Canine Oral Melanomas: A Critical Review of the Literature." Veterinary Sciences 9, no. 5 (April 19, 2022): 196. http://dx.doi.org/10.3390/vetsci9050196.

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Critical appraisal of the available literature for the treatment of canine oral malignant melanoma (OMM) is lacking. This critical review aimed to evaluate the current literature and provide treatment recommendations and possible suggestions for future canine OMM research. PubMed, Web of Science and Google Scholar were searched in June 2021, for terms relevant to treatment of OMM. Inclusion and exclusion criteria were applied and information on clinical response and outcome extracted. Eighty-one studies were included. The overall level of evidence supporting the various canine OMM treatment options was low. The majority of studies included confounding treatment modalities and lacked randomization, control groups and consistency in reporting clinical response and outcomes. Within these limitations, surgery remains the mainstay of therapy. Adjunctive radiotherapy provided good local control and improved median survival times (MST), chemotherapy did not offer survival benefit beyond that of surgery, while electrochemotherapy may offer a potential alternative to radiotherapy. Immunotherapy holds the most promise in extending MST in the surgical adjunctive setting, in particular the combination of gene therapy and autologous vaccination. Prospective, randomized, double-blinded clinical trials, with a lack of confounding factors and reporting based on established guidelines would allow comparison and recommendations for the treatment of canine OMM.

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Bateman, Karen E., Pamela A. Catton, Paul W. Pennock, and Stephen A. Kruth. "0-7-21 Radiation Therapy for the Treatment of Canine Oral Melanoma." Journal of Veterinary Internal Medicine 8, no. 4 (July 1994): 267–72. http://dx.doi.org/10.1111/j.1939-1676.1994.tb03231.x.

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Felizzola, C., V. Araújo, N. Araújo, D. Pinto, and S. Sousa. "Canine Oral Malignant Melanoma: Clinical, Histologic, and Immunohistochemical Aspects of 268 Cases." Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 100, no. 2 (August 2005): 196. http://dx.doi.org/10.1016/j.tripleo.2005.05.050.

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OYAMADA, Toshifumi, Hirofumi TANAKA, Chun-Ho PARK, Hideaki UEKI, Tomoyoshi KOMIYA, and Setsuo ARAI. "Pathology of Canine Oral Malignant Melanoma with Cartilage and/or Osteoid Formation." Journal of Veterinary Medical Science 69, no. 11 (2007): 1155–61. http://dx.doi.org/10.1292/jvms.69.1155.

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Noguchi, Shunsuke, Takashi Mori, Yusami Otsuka, Nami Yamada, Yuki Yasui, Junya Iwasaki, Minami Kumazaki, Kohji Maruo, and Yukihiro Akao. "Anti-oncogenic MicroRNA-203 Induces Senescence by Targeting E2F3 Protein in Human Melanoma Cells." Journal of Biological Chemistry 287, no. 15 (February 21, 2012): 11769–77. http://dx.doi.org/10.1074/jbc.m111.325027.

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MicroRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of their complementary mRNA. We recently reported that miR-203 is down-regulated, and its exogenous expression inhibits cell growth in canine oral malignant melanoma tissue specimens as well as in canine and human malignant melanoma cells. A microRNA target database predicted E2F3 and ZBP-89 as putative targets of microRNA-203 (miR-203). The expression levels of E2F3a, E2F3b, and ZBP-89 were markedly up-regulated in human malignant melanoma Mewo cells compared with those in human epidermal melanocytes. miR-203 significantly suppressed the luciferase activity of reporter plasmids containing the 3′-UTR sequence of either E2F3 or ZBP-89 complementary to miR-203. The ectopic expression of miR-203 in melanoma cells reduced the levels of E2F3a, E2F3b, and ZBP-89 protein expression. At the same time, miR-203 induced cell cycle arrest and senescence phenotypes, such as elevated expression of hypophosphorylated retinoblastoma and other markers for senescence. Silencing of E2F3, but not of ZBP-89, inhibited cell growth and induced cell cycle arrest and senescence. These results demonstrate a novel role for miR-203 as a tumor suppressor acting by inducing senescence in melanoma cells.

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Prouteau, Anais, Stephanie Mottier, Aline Primot, Edouard Cadieu, Laura Bachelot, Nadine Botherel, Florian Cabillic, et al. "Canine Oral Melanoma Genomic and Transcriptomic Study Defines Two Molecular Subgroups with Different Therapeutical Targets." Cancers 14, no. 2 (January 6, 2022): 276. http://dx.doi.org/10.3390/cancers14020276.

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Mucosal melanoma (MM) is a rare, aggressive clinical cancer. Despite recent advances in genetics and treatment, the prognosis of MM remains poor. Canine MM offers a relevant spontaneous and immunocompetent model to decipher the genetic bases and explore treatments for MM. We performed an integrative genomic and transcriptomic analysis of 32 canine MM samples, which identified two molecular subgroups with a different microenvironment and structural variant (SV) content. The overexpression of genes related to the microenvironment and T-cell response was associated with tumors harboring a lower content of SVs, whereas the overexpression of pigmentation-related pathways and oncogenes, such as TERT, was associated with a high SV burden. Using whole-genome sequencing, we showed that focal amplifications characterized complex chromosomal rearrangements targeting oncogenes, such as MDM2 or CDK4, and a recurrently amplified region on canine chromosome 30. We also demonstrated that the genes TRPM7, GABPB1, and SPPL2A, located in this CFA30 region, play a role in cell proliferation, and thus, may be considered as new candidate oncogenes for human MM. Our findings suggest the existence of two MM molecular subgroups that may benefit from dedicated therapies, such as immune checkpoint inhibitors or targeted therapies, for both human and veterinary medicine.

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Murray, Ben, and Kelly L. Bowlt Blacklock. "Pilot Study: Assessing the Expression of Serum Lactate Dehydrogenase and Peripheral Leukocyte Ratios in Canine Oral Malignant Melanoma." Veterinary Sciences 9, no. 8 (August 9, 2022): 421. http://dx.doi.org/10.3390/vetsci9080421.

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Measurement of blood biomarkers such as lactate dehydrogenase (LDH) and peripheral leukocyte ratios have been shown to be of prognostic value in human melanoma patients. Previous veterinary studies have demonstrated that changes in these values are detectable in multiple canine cancer patients. However, to the authors’ knowledge, no studies have yet demonstrated an increase in LDH in canine oral malignant melanoma patients, nor has the effect of metastasis on LDH levels been explored. This retrospective pilot study included 18 dogs, of which 10 were healthy controls, 5 OMM patients with metastasis and 3 without metastasis. Serum LDH was measured and pre-treatment peripheral leucocyte ratios were calculated. LDH was measurable within all patient groups and a statistically significant difference in LDH levels was detected between patients with OMM and healthy controls (p < 0.05); however, no significant difference was detected between patients with or without metastatic disease. This study suggests that serum LDH levels are significantly increased in dogs with OMM compared to healthy controls, paving the way for further research to investigate the prognostic value of this biomarker.

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de Carvalho, Joyce Pires, Marcella Collaneri Carrilho, Denner Santos dos Anjos, Carolina Dagli Hernandez, Laura Sichero, and Maria Lúcia Zaidan Dagli. "Unraveling the Risk Factors and Etiology of the Canine Oral Mucosal Melanoma: Results of an Epidemiological Questionnaire, Oral Microbiome Analysis and Investigation of Papillomavirus Infection." Cancers 14, no. 14 (July 13, 2022): 3397. http://dx.doi.org/10.3390/cancers14143397.

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Oral mucosal melanoma (OMM) is the most common oral cancer in dogs and is very aggressive in this species; its risk factors and etiology are yet to be determined. This study aimed to unravel the risk factors for the development of OMM in dogs and to investigate the possible presence of papillomaviruses as an etiological factor. A case-control study was conducted in 15 dogs with OMM and 15 paired controls whose owners answered an epidemiological questionnaire. Oral swabs from the same dogs were subjected to 16S rRNA sequencing for microbiome analyses. In addition, DNA fragments of OMM had their DNA extracted and amplified by polymerase chain reaction in an attempt to detect canine papillomaviruses. The gingiva was the most frequent anatomical site (47%) of OMM, and most tumors were stage III when diagnosed. Most dogs bearing OMM and the controls had grade 3 periodontal disease, and this factor, along with tartar treatment and tooth brushing, did not differ between cases and controls. Most dogs with OMM and most controls had contact with smokers; there was no statistically significant difference. Canine papillomaviruses were not detected among OMM cases. Tannerella forsythia and Porphyromonas gingivalis were significantly increased in case dogs compared to the controls. As these bacteria are reportedly involved in the pathogenesis of periodontal disease and esophageal cancer in humans, we suggest that they might be risk factors for the development of canine OMM. The limitations of this study include the low number of dogs, and therefore, further studies on canine OMM with larger numbers of animals are encouraged.

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Konradsson, E., M. L. Arendt, K. Bastholm Jensen, H. Thomasson, B. Børresen, K. Petersson, and C. Ceberg. "Intracavitary Electron FLASH Radiotherapy in a Canine Cancer Patient With Oral Malignant Melanoma." International Journal of Radiation Oncology*Biology*Physics 111, no. 3 (November 2021): S31. http://dx.doi.org/10.1016/j.ijrobp.2021.07.097.

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Guillén, Alexandra, Katerina Stiborova, Lorenzo Ressel, Laura Blackwood, Riccardo Finotello, Isabel Amores-Fuster, Nimo Jama, and David Killick. "Immunohistochemical expression and prognostic significance of MAGE-A in canine oral malignant melanoma." Research in Veterinary Science 137 (July 2021): 226–34. http://dx.doi.org/10.1016/j.rvsc.2021.05.009.

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KAWABE, Mifumi, Yuta BABA, Reo TAMAI, Ryohei YAMAMOTO, Masayuki KOMORI, Takashi MORI, and Shigeo TAKENAKA. "Profiling of plasma metabolites in canine oral melanoma using gas chromatography-mass spectrometry." Journal of Veterinary Medical Science 77, no. 8 (2015): 1025–28. http://dx.doi.org/10.1292/jvms.14-0641.

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Schmid, Franziska, Daniela Brodesser, Martin Reifinger, Sara Forte, Pia Semp, Matthias C. Eberspächer‐Schweda, Markus Wolschek, Sabine Brandt, Miriam Kleiter, and Barbara Pratscher. "Canine oral primary melanoma cells exhibit shift to mesenchymal phenotype and phagocytic behaviour." Veterinary and Comparative Oncology 17, no. 3 (May 29, 2019): 211–20. http://dx.doi.org/10.1111/vco.12464.

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Prouteau, Anais, Florian Chocteau, Clotilde Brito, Edouard Cadieu, Aline Primot, Nadine Botherel, Frédérique Degorce, et al. "Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma." Veterinary and Comparative Oncology 18, no. 2 (September 13, 2019): 214–23. http://dx.doi.org/10.1111/vco.12536.

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Journal articles on the topic 'Canine oral melanoma'

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