RESUMO
PURPOSE: The tyrosine kinase receptor Tie2 and its ligands, the angiopoietins (Angs), play important roles in vascular integrity and neovascularization, modulating vascular endothelial growth factor (VEGF) activity. To elucidate the potential role of Angs and the Tie2 system in retinopathy of prematurity (ROP), we have investigated the expression of Angs, Tie2 and VEGF within fibroproliferative membranes in ROP. METHODS: Fibroproliferative membranes were obtained from 38 cases with stage 5 ROP at the time of vitrectomy. Membranes were fixed in formalin and embedded in paraffin. Each specimen was serially sectioned for immunohistochemistry. Polyclonal antibodies specific for Ang1, Ang2, Tie2 and VEGF were used for immunostaining. Immunoreactivity for von Willebrand factor (factor VIII) was also assessed to confirm the identity of vascular endothelial cells. RESULTS: Positive staining for Tie2 was observed in 23 of 38 specimens (60.5%). Tie2 was localized in vascularized regions of fibrovascular membranes and was co- expressed with VEGF and factor VIII. Ang2 stained positively in 18 of 38 (47.3%) serial sections where Tie2 was present, and was also co-expressed with VEGF and factor VIII. Ang1 was not generally observed in these specimens (3/38). CONCLUSIONS: VEGF and Ang2-Tie2 interactions may play an important role in the pathogenesis of ROP.
Assuntos
Indutores da Angiogênese/metabolismo , Fatores de Crescimento Endotelial/metabolismo , Inibidores Enzimáticos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfocinas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Neovascularização Retiniana/metabolismo , Retinopatia da Prematuridade/metabolismo , Angiopoietina-2 , Peso ao Nascer , Feminino , Fibrose , Técnica Indireta de Fluorescência para Anticorpo , Idade Gestacional , Humanos , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Masculino , Membranas , Receptor TIE-2 , Retina/metabolismo , Retina/patologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Fator de von Willebrand/metabolismoRESUMO
BACKGROUND: In a recent in vitro study we demonstrated a specifically-targeted killing of CEA-expressing cells by a recombinant bifunctional retrovector displaying an scFv antibody to CEA and carrying the iNOS gene. In this study, we tested whether a gene therapy using the recombinant retrovirus could inhibit the growth of CEA-expressing tumors in mice. MATERIALS AND METHODS: SCID mice were inoculated s.c. on the back with CEA-expressing MKN-45 cells on day 0. The recombinant viral particles were injected into the inoculated sites on days 3, 5 and 7 and tumor size was measured every 5 days. RESULTS: The s.c. administration of the recombinant retrovirus produced a marked growth inhibition of MKN-45 tumors in SCID mice. When the actual tumor weights were measured 50 days after initiation of treatment, about 70% reduction was observed in the treated group as compared to the control groups. CONCLUSION: This approach may also be applied to other tumor antigens expressed on cancer cells and is a step towards the cell specific suppression of tumorigenicity.
