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Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade
Experimental & Molecular Medicine ; : e52-2013.
Artigo em Inglês | WPRIM | ID: wpr-152451
ABSTRACT
Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Neoplasias Gástricas / Proteínas Recombinantes de Fusão / Protocolos de Quimioterapia Combinada Antineoplásica / Apoptose / Receptor ErbB-2 / Ensaios Antitumorais Modelo de Xenoenxerto / Receptores de Fatores de Crescimento do Endotélio Vascular / Linhagem Celular Tumoral / Fator A de Crescimento do Endotélio Vascular / Proliferação de Células Tipo de estudo: Estudo prognóstico Limite: Animais / Humanos Idioma: Inglês Revista: Experimental & Molecular Medicine Ano de publicação: 2013 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Neoplasias Gástricas / Proteínas Recombinantes de Fusão / Protocolos de Quimioterapia Combinada Antineoplásica / Apoptose / Receptor ErbB-2 / Ensaios Antitumorais Modelo de Xenoenxerto / Receptores de Fatores de Crescimento do Endotélio Vascular / Linhagem Celular Tumoral / Fator A de Crescimento do Endotélio Vascular / Proliferação de Células Tipo de estudo: Estudo prognóstico Limite: Animais / Humanos Idioma: Inglês Revista: Experimental & Molecular Medicine Ano de publicação: 2013 Tipo de documento: Artigo