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Doctoral Thesis
DOI
https://doi.org/10.11606/T.10.2023.tde-16022024-100713
Document
Author
Full name
Ivan Braga Rodrigues de Souza
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Nishiyama, Ana Claudia Oliveira Carreira (President)
Cardoso, Vinicius Kannen
Fratini, Paula
Lobba, Aline Ramos Maia
Santos, Stefanie Vanessa
Title in Portuguese
Análise de marcadores proteicos em neoplasias mamárias caninas e felinas: uma abordagem bioinformática integrativa na oncologia veterinária
Keywords in Portuguese
Glândula mamária
Imuno-histoquímica
Neoplasia mamária
Oncologia molecular
Prognóstico
Abstract in Portuguese
As neoplasias mamárias são frequentes em cães e gatos, sendo o tipo de câncer mais comum em cadelas e a terceira mais descrita no gato doméstico, e com manifestações clínicas geralmente semelhantes à humana. A neoplasia mamária é a mais diagnosticada e a principal causa de mortalidade relacionada ao câncer em mulheres e cadelas existindo interesse no seu prognóstico, tratamento e no desenvolvimento como ferramenta para oncologia comparada, pois, embora o fenômeno seja bem conhecido a causa não é, e seu estudo integrado oferece oportunidade para aprender mais sobre o câncer. Dessa forma, devido ao relativo tempo de vida longo, ao tamanho da espécie e similaridade fisiológica, as doenças caninas são de especial interesse para a medicina humana. Este estudo analisou e comparou o perfil de expressão de diversos marcadores proteicos em amostras de tecido mamário normal, hiperplásico e neoplásico (carcinomas) de cadelas e gatas. As amostras foram categorizadas rigorosamente de acordo com critérios histopatológicos. A análise imuno- histoquímica, utilizando diversos anticorpos, revelou importantes modificações moleculares durante a carcinogênese mamária nas espécies. Houve aumento da expressão de marcadores pró-inflamatórios (COX-2), pró-angiogênicos (CD31, VEGF), de resistência à apoptose (Bcl-2) e redução de proteínas supressoras (P53). As correlações positivas entre esses mediadores sustentam sua atuação integrada e sinérgica na promoção do crescimento neoplásico. As técnicas histológicas de coloração de vermelho de Picrossírius, Azul de Alcian e detecção de calcificações distróficas evidenciaram alterações relevantes nos componentes matriciais do tipo colágenos, mucinas ácidas e elementos fibrosos, respectivamente. Este estudo contribui para o conhecimento translacional da biologia do carcinoma mamário nessas espécies, trazendo informações sobre interações moleculares e identificando potenciais biomarcadores e alvos terapêuticos. A integração de dados clínicos, histopatológicos e imunofenotípicos fornece uma visão multifacetada deste importante tumor veterinário.
Title in English
Protein marker analysis in canine and feline mammary neoplasms: an integrative bioinformatics approach in veterinary oncology
Keywords in English
Immunohistochemistry
Mammary gland
Mammary neoplasm
Molecular oncology
Prognosis
Abstract in English
Mammary neoplasms are common in dogs and cats, being the most common type of cancer in dogs and the third most described in domestic cats, and with clinical manifestations generally similar to those in humans. Mammary neoplasia is the most diagnosed and the main cause of cancer-related mortality in women and dogs. There is interest in its prognosis, treatment and development as a tool for comparative oncology, because, although the phenomenon is well known, the cause is not, and its integrated study provides an opportunity to learn more about cancer. Therefore, due to the relative long lifespan, size of the species and physiological similarity, canine diseases are of special interest to human medicine. This study analyzed and compared the expression profile of several protein markers in samples of normal, hyperplastic and neoplastic mammary tissue (carcinomas) from dogs and cats. Samples were rigorously categorized according to histopathological criteria. Immunohistochemical analysis, using several antibodies, revealed important molecular changes during mammary carcinogenesis in the species. There was an increase in the expression of pro- inflammatory markers (COX-2), pro-angiogenic markers (CD31, VEGF), resistance to apoptosis (Bcl-2) and a reduction in suppressor proteins (P53). The positive correlations between these mediators support their integrated and synergistic action in promoting neoplastic growth. The histological techniques of Picrosirius red and Alcian blue staining and detection of dystrophic calcifications showed relevant changes in matrix components such as collagens, acid mucins and fibrous elements, respectively. This study contributes to the translational knowledge of the biology of mammary carcinoma in these species, providing information on molecular interactions and identifying potential biomarkers and therapeutic targets. The integration of clinical, histopathological and immunophenotypic data provides a multifaceted view of this important veterinary tumor.
 
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Release Date
2026-03-27
Publishing Date
2024-04-05
 
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