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Doctoral Thesis
DOI
10.11606/T.10.2014.tde-23032015-122632
Document
Author
Full name
Sonia Elisabete Alves de Lima Will
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Rici, Rose Elí Grassi (President)
Assís Neto, Antônio Chaves de
Giorgi, Ricardo Rodrigues
Katayama, Maria Lucia Hirata
Maria, Durvanei Augusto
Title in Portuguese
Efeito da terapia "in vitro" com célula tronco de medula óssea em tumores mamários caninos
Keywords in Portuguese
Angiogênese
Metástase
Terapia celular
Tumor de mama
Abstract in Portuguese
O tumor mamário é a segunda neoplasia maligna mais incidente em cães, com uma elevada taxa de mortalidade. Em cães, constituem aproximadamente 52% de todos os tumores que afetam as fêmeas, possuindo uma elevada heterogeneidade biológica e histomorfológica, sendo que 50% são malignos. As neoplasias, independentemente de suas causas primárias, apresentam distúrbios no controle do ciclo celular, o que acaba gerando um aumento na proliferação celular, perda da diferenciação e formação de massas tumorais. Na gênese das neoplasias mamárias estão envolvidos fatores de natureza genética, ambiental e hormonal. O objetivo deste trabalho foi avaliar "in vitro" o efeito da terapia com célula- tronco da medula óssea canina de feto em tumores mamários canino. Após a avaliação histopatológica os tumores foram divididos em grupos de grau I (adenocarcinoma, sem metástase), grau II (carcinoma com metástase regionais) e grau III (carcinomas com metástases sistêmicas). As células dos tumores mamários caninos (TM) e as células - tronco de medula óssea de feto canina (CTMs) foram caracterizadas antes e após o tratamento utilizando marcadores de proliferação, angiogênese e da resposta inflamatória através da citometria de fluxo. A expressão de marcadores de proliferação celular Ki67 foi maior nas linhagens tumorais dos carcinomas grau III, o mesmo observado para os marcadores que regulam a angiogênese e migração celular como VEGFR1, CD44, COX-2 e EGFR. Foi possível observar nas culturas celulares de TM a redução do potencial elétrico mitocondrial alterando permeabilidade da membrana ativando a caspase 3 e reduzindo a Bcl-2, sugerindo que a CTM apresenta efeitos antitumorais pela indução de apoptose e efeitos antiproliferativos da expressão de COX-2 e IL-6 inibindo a proliferação celular levando ao acúmulo das células na fase G0/G1. . A terapia celular com CTMs proporciona novas expectativas para o tratamento de diversas patologias que acometem diferentes espécies.. Desta forma, os resultados os resultados obtidos pela expressão das TM tratadas com CTM pode apresentar como uma nova perspectiva no tratamento de tumores em cadelas.
Title in English
Effect of therapy "in vitro" with stem cell of bone marrow mammary tumors canine
Keywords in English
Angiogenesis
Breast tumor
Cell therapy
Metastasis
Abstract in English
The breast tumor is the second most frequent malignancy in dogs, with a high mortality rate. In dogs, they constitute approximately 52% of all tumors affecting female, having a high biological and histomorphological heterogeneity, and 50% are malignant. Neoplasms, regardless of their root causes, have disturbances in cell cycle control, which ends up generating an increase in cell proliferation, differentiation loss and formation of tumor masses. In the genesis of mammary tumors are involved genetic, environmental and hormonal factors nature. The objective of this study was to evaluate "in vitro" the effect of therapy with stem cell-canine bone marrow fetus in canine mammary tumors. After histopathological evaluation tumors were divided into grade I groups (adenocarcinoma without metastasis), grade II (carcinoma with regional metastasis) and grade III (carcinomas with metastatic disease) .The cells of canine mammary tumors (TM) and cells - bone marrow stem canine fetuses (MSCs) were characterized before and after treatment using proliferation markers, angiogenesis and inflammatory response by flow cytometry. The expression of cell proliferation markers Ki67 was higher in tumor cell lines of the carcinomas grade III, the same was observed for markers that regulate angiogenesis and cell migration as VEGFR1, CD44, COX-2 and EGFR. It was observed in TM cell cultures to reduce the electric potential changing mitochondrial membrane permeability by activating caspase 3 and reduces Bcl-2, suggesting that MSC has antitumor effects by inducing apoptosis and antiproliferative effects of COX-2 expression and IL-6 inhibiting cell proliferation leading to an accumulation of cells in G0 / G1 phase. Cell therapy MSCs provides new expectations for the treatment of various pathologies affecting different species. Thus, the results the results obtained by the expression of TM-treated MSC can present as a new approach in the treatment of tumors in dogs..
 
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Publishing Date
2015-08-07
 
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