Vascular endothelial growth factor as a biomarker for endostatin gene therapy

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Braga, Marina Souza [UNIFESP]
Turaca, Thiago Lauro [UNIFESP]
Foguer, Karen [UNIFESP]
Barbosa Chaves, Karen Cristina [UNIFESP]
Pesquero, Joao Bosco [UNIFESP]
Chammas, Roger
Schor, Nestor [UNIFESP]
Bellini, Maria Helena [UNIFESP]
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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.
Biomedicine & Pharmacotherapy. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 67, n. 6, p. 511-515, 2013.