Made available in DSpace on 2016-05-17T16:51:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-08-06. Added 1 bitstream(s) on 2016-05-17T16:54:50Z : No. of bitstreams: 1 000864249.pdf: 7320039 bytes, checksum: 72267d35491b03d5cd6737c361481e7c (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrossarcoma cell line were tested regarding to their susceptibility to CDV infection, apoptosis, mitochondrial membrane potential (MMP) and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication induced cytopathic effect and > 45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDV M gene expression were positively correlated in all cell lines. In addition, MMP was highly associated with increase in virus titres (p<0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy

Resumo:A Viroterapia oncolítica é uma nova estratégia para o tratamento de câncer em seres humanos e também em animais de companhia. O vírus da cinomose canina (CDV), um paramixovírus, tem se mostrado ser oncolítico através da indução de apoptose em células tumorais derivadas de cães, ainda que o mecanismo subjacente a esta acção inibidora seja pouco compreendida. Neste estudo, três linhagens de células tumorais mamarias humanas e uma linhagem celular derivada de adenofibrossarcoma canino foram testados quanto à sua suscetibilidade à infecção por CDV, a apoptose, o potencial de membrana mitocondrial (MMP) e a expressão de necrose tumoral-alfa induzida pela proteína de fator 8 (TNFAIP8 ). A replicação CDV induziu o efeito citopático e > 45% das células infectadas foram consideradas no âmbito de morte e/ou apoptose tardia sob necrose. TNFAIP8 e expressão gênica CDV foram positivamente correlacionadas em todas as linhagens celulares. Além disso, a MMP foi altamente associada com o aumento nos títulos de vírus (p <0,005). Assim, estes resultados sugerem fortemente que ambas as células tumorais mamárias humanas e caninas são potenciais candidatos para estudos sobre a terapia do câncer induzido por CDV / Abstract:Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrossarcoma cell line were tested regarding to their susceptibility to CDV infection, apoptosis, mitochondrial membrane potential (MMP) and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication induced cytopathic effect and > 45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDV M gene expression were positively correlated in all cell lines. In addition, MMP was highly associated with increase in virus titres (p<0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy / Orientador:Tereza Cristina Cardoso da Silva / Banca:Andréa Fontes Garcia / Banca:Roberto Gameiro de Carvalho / Mestre