Vascular endothelial growth factor as a biomarker for endostatin gene therapy

Autor(es)

Braga, Marina Souza ^{[1, 2]} ; Turaca, Thiago Lauro ^[3] ; Foguer, Karen ^{[1, 2]} ; Barbosa Chaves, Karen Cristina ^{[1, 2]} ; Pesquero, Joao Bosco ^[3] ; Chammas, Roger ^[4] ; Schor, Nestor ^[1] ; Bellini, Maria Helena ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo - Brazil

^[2] IPEN CNEN, Dept Biotechnol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Radiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 67, n. 6, p. 511-515, JUL 2013.
• Citações Web of Science: 5

Resumo

Renal cell carcinoma (RCC) is characterized by high vascular endothelial growth factor (VEGF) production and, consequently, excessive angiogenesis. Several strategies have been developed to target angiogenesis as a method for treating metastatic RCC (mRCC). Endostatin (ES) is a C-terminal fragment of collagen XVIII that has antiangiogenic activity. The aim of this study was to investigate the predictive value of circulating VEGF-A in a murine model of mRCC after ES gene therapy. ES therapy did not affect the levels of collagen XVIII/ES or ES in the tissue. The circulating level of ES was increased in the control and ES-treated groups (normal vs. control, P < 0.05 and ES-treated vs. control, P < 0.001), and the intratumoral vessels were significantly decreased (ES-treated vs. control, P < 0.05). ES therapy decreased the VEGF mRNA levels. The tissue and circulating levels of VEGF in the control group were significantly higher than normal (P < 0.01 and P < 0.05, respectively). Treatment with ES significantly reduced the VEGF concentrations in both compartments (P < 0.001 for tissue and P < 0.05 for plasma). Our findings indicate that in addition to the directly targeted tumor vessels, ES exerts its antitumor effect by down-regulating VEGF gene expression in renal tumor cells. Additionally, our findings point to the predictive value of VEGF for ES therapy. (C) 2013 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 10/18969-0 - Estudo da regulação do NF-kB no carcinoma renal metastático após terapia gênica com endostatina
• Beneficiário: Maria Helena Bellini Marumo
• Modalidade de apoio: Auxílio à Pesquisa - Regular