Avaliação da heterogeneidade da expressão de HER-2 e efeito antitumoral do lapatinibe em osteossarcomas caninos
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Data
2022-07-29
Autores
Franzoni, Mayara Simão
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Universidade Estadual Paulista (Unesp)
Resumo
O câncer é uma das causas de maior mortalidade dos cães, sendo o osteossarcoma um tipo de neoplasia óssea que tem grande incidência nessa espécie. Pesquisa recentes demonstraram que o HER-2, um receptor de tirosina quinase, é expressado nesse tipo de tumor, e está associado a baixa sobrevida e resistência quimioterápica, além disso, estimula a diferenciação celular, migração, apoptose e angiogênese, portanto, o bloqueio desta via pode impedir a diferenciação e a migração celular, induzir apoptose das células neoplásicas e diminuir a angiogênese. Atualmente o tratamento de eleição para o osteossarcoma canino é a amputação do membro acometido associado à quimioterapia, normalmente com Doxorrubicina. Em função dos novos achados em relação ao HER-2, novas terapias estão em desenvolvimento, sendo o Lapatinibe um fármaco que inibe a fosforilazação desse receptor, e será testado em culturas celulares de osteossarcomas coletados no Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da UNESP de Botucatu, no intuito de comparar seu efeito antineoplásico com o efeito da Doxorrubicina, além de caracterizar a expressão do HER-2 nessas amostras, uma vez que há poucos estudos com essas informações em relação ao osteossarcoma em cães.
Cancer is one of the most important causes of death in dogs, and osteosarcoma is a type of bone cancer with high incidence in dogs. Recent studies has shown that HER-2, a tyrosine kinase receptor, is expressed in canine osteosarcoma, and is associated with poor overall survival and chemotherapy resistance. In addition to stimulating cell differentiation, migration, apoptosis and angiogenesis. Therefore blocking HER2 pathway may prevent cell differentiation and migration, induce neoplastic cell apoptosis and decrease angiogenesis. The aim of this study was to evaluate intra and inter-tumor HER-2 labeling through immunohistochemistry, and to correlate these data with clinical and histopathological aspects. We observed that the highest score of marking and staining of this marker can be correlated with the negative aspects of the patients, in addition, intratumoral heterogeneity was significant both in histopathological characteristics and in HER-2 marking, a situation that should be considered to establish new therapeutic approaches for osteosarcoma, as only a biopsy fragment may not be significant for the whole.
Cancer is one of the most important causes of death in dogs, and osteosarcoma is a type of bone cancer with high incidence in dogs. Recent studies has shown that HER-2, a tyrosine kinase receptor, is expressed in canine osteosarcoma, and is associated with poor overall survival and chemotherapy resistance. In addition to stimulating cell differentiation, migration, apoptosis and angiogenesis. Therefore blocking HER2 pathway may prevent cell differentiation and migration, induce neoplastic cell apoptosis and decrease angiogenesis. The aim of this study was to evaluate intra and inter-tumor HER-2 labeling through immunohistochemistry, and to correlate these data with clinical and histopathological aspects. We observed that the highest score of marking and staining of this marker can be correlated with the negative aspects of the patients, in addition, intratumoral heterogeneity was significant both in histopathological characteristics and in HER-2 marking, a situation that should be considered to establish new therapeutic approaches for osteosarcoma, as only a biopsy fragment may not be significant for the whole.
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Palavras-chave
Osteossarcoma, HER-2, Lapatinibe