Endostatin neoadjuvant gene therapy extends survival in an orthotopic metastatic mouse model of renal cell carcinoma

Author(s)

Braga, Marina de Souza ^{[1, 2]} ; Chaves, Karen Barbosa ^[1] ; Chammas, Roger ^[3] ; Schor, Nestor ^[1] ; Bellini, Maria Helena ^{[1, 2]}

Affiliation

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

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

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

• Document type: Journal article
• Source: BIOMEDICINE & PHARMACOTHERAPY; v. 66, n. 4, p. 237-241, JUN 2012.
• Web of Science Citations: 6

Abstract

Despite recent advances in targeted therapy, renal cell carcinoma (RCC) remains one of the most lethal urologic malignancies. Approximately 30% of patients with localised RCC will develop metastases after curative surgery. Presurgical therapy has been explored for treatment of localised RCC. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential use of an antiangiogenic agent as a neoadjuvant therapy in an orthotopic metastatic mouse model of RCC. BALB/c mice bearing Renca cells were treated before nephrectomy with NIH/3T3-LendSN cells. At the end of the experiment, ES serum levels were measured. Primary and metastatic tumour area and microvascular area were determined. In the survival studies, mice were monitored daily until they died. ES serum levels in treated mice were higher in the control group (P < 0.05). The median primary tumour area and the mean microvascular area were significantly lower in the ES-treated group compared to control group (P < 0.05). The proliferation of Renca cells in the ES-treated group was significantly reduced compared with the control group (P < 0.01). ES therapy led to a significant reduction in the number of pulmonary metastatic nodules compared with the control group (P < 0.01). Kaplan-Meier survival curves showed that the probability of survival was significantly higher in mice receiving ES therapy (P = 0.0243, Log-Rank test). Our results indicated that neoadjuvant ES gene therapy has the potential to decrease tumour burden, extend survival, and may have clinical benefit in the management of RCC. (C) 2011 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 10/18969-0 - NF-kB regulation in the renal cell carcinoma after endostatin gene therapy
• Grantee: Maria Helena Bellini Marumo
• Support Opportunities: Regular Research Grants