Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas.
Analysis of the expression of inflammatory markers before starting treatment in human patients with cancer helps to predict outcomes and prognosis; however, there have been few studies on this topic in veterinary medicine. The present study aimed to evaluate inflammatory indices before treatment with autologous antitumor vaccine alone or this vaccine plus metronomic chemotherapy (MC) to predict response and prognosis. The indices included the neutrophil–lymphocyte ratio (NRL), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), systemic immune-inflammation index (SII), C-reactive-protein–albumin ratio (CRP/ALB), lactate dehydrogenase level (LDH), frequency of blood lymphocyte subsets (CD4+, CD8+, Treg, and CD4/CD8 ratio) and frequency of blood myeloid-derived suppressor cells (MDSCs: monocytic [M]- MDSCs, and granulocytic [PMN]-MDSCs). Blood samples were collected from 25 dogs with oral melanoma treated with the autologous antitumor vaccine and from nine dogs that received MC plus vaccine before surgery. There were no statistically significant differences in the progression-free survival (PFS) or overall survival (OS) between the groups. In addition to the clinical stage, the CRP/ALB ratio and blood circulating Tregs in the univariate analysis showed an association with PFS and OS, and thus were selected for multivariable analysis. The CRP/ALB ratio was associated with PFS [hazard ratio (HR), 1.1; 95% confidence interval (CI), 1.0–1.1; p = 0.017] and OS [HR, 1; 95%CI, 1.0–1.1; p = 0.023]. Similarly, Treg was associated with PFS (HR, 1.6; 95% CI, 1.2–2.1; p = 0.001) and OS (HR, 1.6; 95% CI, 1.2–2.1; p = 0.001). Furthermore, canine patients with a CRP/ALB ratio above the cut-off point of 1.9 (established by receiver operating characteristic curve analysis) had worse PFS and OS, indicating the impact of the preoperative CRP/ALB ratio on the PFS and OS of dogs with oral melanoma. The CRP/ALB ratio and frequency of circulating Tregs are potential prognostic markers in dogs with oral melanoma.
O uso tradicional de espécies nativas para fins terapêuticos apresenta benefícios diretos e imediatos para distintas populações locais, seja pelo cuidado com a saúde ou pela possibilidade de produção e geração de renda. Porém, podem colaborar com a degradação dos ecossistemas, pelo extrativismo e superexploração, que têm colaborado com o avanço do desequilíbrio ecológico. Deste modo, o objetivo desse estudo foi utilizar a Maytenus ilicifolia para exemplificar o que ocorre em relação à exploração e uso de plantas medicinais no Brasil. O estudo foi conduzido a partir da literatura científica, sendo a busca realizada nas plataformas Scielo, Research-Gate, Scoppus, Web-of-Science e Google Acadêmico. As palavras espinheira-santa e Maytenus ilicifolia foram utilizadas nas buscas. Foram selecionados os artigos que abordassem os aspectos: botânica, ecologia, etnobotânica, fitoquímica, fitotecnia e adulterações. Como resultados, verificamos um grande número de publicações sobre fitoquímica, que a espécie sofre com extrativismo e falsificações, e que o manejo em agroecossistemas é ainda incipiente. Concluímos que são necessários incentivos em políticas públicas para pesquisas, produção e divulgação da espécie. Sua inserção em cadeias produtivas configura a sua conservação on farm, possibilitando um passo efetivo para conservação e preservação da espécie. Palavras-chave: agroecologia; conservação on farm; Maytenus ilicifolia; sociobiodiversidade; agricultura familiar. Espinheira-santa: from extractivism to sustainable production ABSTRACT: The traditional use of native species for therapeutic purposes has direct and immediate benefits for different local populations, whether for health care or the possibility of production and income generation. However, they can collaborate with the degradation of ecosystems, through extractivism and overexploitation, which have collaborated with the advancement of ecological imbalance. Thus, the objective of this study was to use Maytenus ilicifolia to exemplify what happens in relation to the exploration and use of medicinal plants in Brazil. The study was conducted based on the scientific literature, and the search was carried out on the Scielo, Research-Gate, Scoppus, Web-of-Science and Google Scholar platforms. The words espinheira-santa and Maytenus ilicifolia were used in the searches. Articles that addressed the following aspects were selected: botany, ecology, ethnobotany, phytochemistry, phytotechnics and adulterations. As a result, we verified many publications on phytochemistry, that the species suffers from extractivism and forgery, and that management in agroecosystems is still incipient. We conclude that public policy incentives are needed for research, production and dissemination of the species. Its insertion in production chains configures its conservation on farm, enabling an effective step towards conservation and preservation of the species. Keywords: agroecology; conservation on farm; Maytenus ilicifolia; sociobiodiversity; family farming.
Dedicatória Dedico essa tese:A minha família, à minha mãe Elenice, ao meu pai José Roberto, à minha irmã Jennifer e ao meu sobrinho Cauê que com muito carinho e apoio, não mediram esforços para que eu chegasse até esta etapa da minha vida.Aos meus queridos companheiros Jolie, Jasmim, Juquinha e Jade. Foi uma honra cuidar de vocês descansem em paz! A todos os animais e seus responsáveis que participaram da pesquisa e a tornou possível.Aos animais que são a minha paixão e motivação para a busca por conhecimento e atualização constante. AgradecimentosAgradeço imensamente a minha orientadora prof a . Dr a . Cristina de Oliveira Massoco Salles Gomes pela oportunidade, carinho, paciência e confiança. Sem o seu apoio eu não teria finalizado esse trabalho e muito obrigada pela sua generosidade e pelo seu cuidado no momento em que mais precisei. Obrigada pelas conversas e pelos ensinamentos pessoais e profissionais.
Canine melanoma is a frequently-occuring neoplasm in dogs and presents as malignant and highly metastatic in this context, studies that contribute to the understanding of the tumor microenvironment in melanoma include the role of galectins. Galectins are proteins of the family of animal lectins that display carbohydrate recognition domains. Galectin-1 and galectin-3 are associated with neoplastic transformation, neoplastic cell survival, angiogenesis, immune system evasion, and metastasis. The goal of this study was to establish a correlation between expression patterns of galectin-1 and galectin-3 and the different degrees of aggressiveness of canine melanoma, as well as to determine serum concentration of galectin-3 in dogs with melanoma. Galectin-1 and galectin-3 expression was analyzed by immunohistochemistry in 30 canine melanomas, six melanocytomas and nine metastatic lymph nodes from patients whose primary tumors were also processed and analyzed. Serum samples from 30 dogs were collected and galectin-3 concentration was determined by ELISA and compared to the samples of 10 healthy dogs. Canine melanoma samples expressed galectin-1 in the cytoplasm and presented a variable pattern of galectin-3 staining depending on melanoma aggressiveness. We observed a decrease in the percentage of cells with cytoplasmic galectin-3 immunolabeling simultaneous to the increased nuclear staining intensity, while there was also a decrease in the percent frequency of nuclear galectin-3 immunolabeled cells according to progression of melanoma, comparing the least to the most aggressive cases. Dogs with melanoma had increased serum levels of galectin-3 when compared to healthy animals, suggesting its potential biomarker of patients with melanoma.
O melanoma canino é uma neoplasia frequente em cães, tem um caráter maligno, invasivo, com potencial metastático e, neste contexto, estudos acerca do envolvimento das galectinas se justifica para ampliar o conhecimento do microambiente tumoral desta neoplasia. As galectinas são proteínas da família das lectinas animais que apresentam domínios de reconhecimento de carboidratos e podem estar localizadas no núcleo, no citoplasma, na superfície de células e secretadas em diversos tecidos. Acredita-se que principalmente a galectina-1 (gal-1) e a galectina-3 (gal-3) estejam associadas à transformação neoplásica, sobrevivência da célula neoplásica, angiogênese, evasão do sistema imune e formação de metástases. A gal-1 está principalmente relacionada com a transformação tumoral e evasão do sistema imune. A gal-3 está principalmente associada com a angiogênese, desenvolvimento de metástases pelo aumento da motilidade e adesão entre as células neoplásicas e adesão entre as células neoplásicas e o endotélio, além de contribuir para a evasão do sistema imune. O objetivo do estudo foi verificar o padrão de expressão de gal-1 e gal-3 nos diferentes graus de agressividade do melanoma canino, além de avaliar a concentração sérica de gal-3 e comparar com cães clinicamente saudáveis. Foram analisadas a expressão de gal-1 e gal-3 em 30 fragmentos de melanoma canino, seis fragmentos de melanocitoma e nove fragmentos de linfonodos metastáticos. Foi realizada a dosagem sérica de gal-3 em 30 cães com melanoma e comparada a 10 cães clinicamente saudáveis. O melanoma canino expressou gal-1 principalmente no citoplasma e expressou um padrão variável de gal-3 no citoplasma e no núcleo. Em relação à expressão de gal-3 observou-se que conforme a agressividade do melanoma houve diminuição da frequência de células com marcação citoplasmática e um aumento da intensidade de marcação nuclear com concomitante diminuição da frequência de células com marcação nuclear. Os cães com melanoma apresentaram aumento dos níveis séricos de gal-3 antes da exérese da neoplasia quando comparados aos animais clinicamente saudáveis, mostrando o seu potencial uso como biomarcador do melanoma. Palavras chave: Galectina-1. Galectina-3. Neoplasia. Imunoistoquímica. Canino. ABSTRACT GARCIA, J. S. Evaluation of galectins expression in canine melanoma. [Avaliação da expressão das galectinas no melanoma canino]. 2017. 96 f. Dissertação (Mestrado em Ciências) -Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, 2017.Canine melanoma is a frequent neoplasm in dogs. It has a malignant, invasive and metastatic potential. In this context, studies about the involvement of galectins are justified to increase the knowledge of melanoma tumor microenvironment. Galectins are proteins of the animal lectins family, that display carbohydrate recognition domains and may be located in the nucleus, cytoplasm, cell surface, as well as secreted in various tissues. Galectin-1 (Gal-1) and galectin-3 (Gal-3) are associated with neoplastic transformation, neopla...
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