RESUMEN
Feline iris melanoma, the most common feline intraocular tumour, has a reported metastatic rate of 19-63%. However, there is a lack of knowledge about its molecular biology. Previous studies have reported that feline iris melanomas do not harbour mutations comparable to common mutations found in their human counterpart. Nevertheless, there are differences in the gene expression patterns. The aim of this study was to investigate the protein expression of B-RAF oncogene serine/threonine kinase (BRAF), G protein subunit alpha q (GNAQ) and 11 (GNA11), KIT proto-oncogene receptor tyrosine kinase (KIT), and Ras association family member 1 (RASSF1) in feline iris melanomas. Fifty-seven formalin-fixed paraffin embedded (FFPE) iris melanomas and 25 FFPE eyes without ocular abnormalities were stained with antibodies against the respective proteins using immunofluorescence. Averaged pixel intensities/µm2 and percentage of stained area from total tissue area were measured and the results were compared. Compared to the control group, iris melanomas showed overexpression of BRAF, GNAQ, GNA11 and KIT. The higher expression of BRAF, GNAQ, GNA11 and KIT in feline iris melanomas suggest that these proteins may play a key role in the development of feline iris melanomas and KIT may present a possible target for future therapies in cats with feline iris melanomas.
Asunto(s)
Enfermedades de los Gatos/metabolismo , Neoplasias del Iris/veterinaria , Melanoma/veterinaria , Animales , Gatos , Femenino , Técnica del Anticuerpo Fluorescente/veterinaria , Subunidades alfa de la Proteína de Unión al GTP/biosíntesis , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/biosíntesis , Neoplasias del Iris/metabolismo , Melanoma/metabolismo , Biosíntesis de Proteínas , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas B-raf/biosíntesis , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Proteínas Supresoras de Tumor/biosíntesisRESUMEN
Feline ocular melanomas show a high malignant behaviour, but adjunctive therapies are non-existent. The aim of this pilot study was to determine, whether feline ocular melanomas harbour mutations comparable to mutations in human melanomas and to evaluate the gene expression status of genes known to be involved in initiation and progression of human melanomas. Mutation hotspot regions of several genes of feline ocular melanomas were analysed by DNA sequencing and RNA expression levels of the respective genes and others were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). Common mutations found in human melanomas are not present in feline tumours. Gene expression analysis revealed a significant upregulation of KIT and LTA4H, as well as a downregulation of GNAQ, GNA11, BRAF and RASSF1 in feline ocular melanomas. As KIT seems to harbour a potential as target gene in human uveal melanomas, future studies should further investigate the potential of KIT as target for adjunctive therapy in feline ocular melanomas.
Asunto(s)
Enfermedades de los Gatos/genética , Neoplasias del Ojo/veterinaria , Melanoma/veterinaria , Animales , Enfermedades de los Gatos/metabolismo , Gatos , Neoplasias del Ojo/genética , Neoplasias del Ojo/metabolismo , Femenino , Perfilación de la Expresión Génica/veterinaria , Regulación Neoplásica de la Expresión Génica/genética , Masculino , Melanoma/genética , Melanoma/metabolismo , Mutación/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinariaRESUMEN
In 217 cases of glossopharyngeal neuralgia seen at the Mayo Clinic between 1922 and 1977, the disease was more common in patients older than 50 years (57%), but also occurred in 43% who were between 18 and 50. Spontaneous remissions were noted by 161 patients, but 37 had no periods of pain relief. Syncope was rarely a problem. Involvement was bilateral in 12%. The combination of glossopharyngeal and trigeminal neuralgia was found in 25 patients. Positive results on the cocaine test in 112 of 125 patients aided in diagnosis. Carbamazepine is the favored medication. Early surgical experience consisted of extracranial avulsion of the glossopharyngeal nerve or intracranial section at the jugular foramen; since 1948, surgical treatment has included section of the glossopharyngeal nerve and usually the upper rootlets of the vagus nerve and additional section of the fifth cranial nerve when trigeminal neuralgia was associated. Good relief of pain was obtained surgically in 110 patients.