title: Endostatin neoadjuvant gene therapy extends survival in an orthotopic metastatic mouse model of renal cell carcinoma.
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.
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: de Souza Braga
authors.forename: Karen Barbosa
authors.initials: KB
authors.lastname: Chaves
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Bellini
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D043169:Endostatins / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D020360:Neoadjuvant Therapy / Q000379:methods; D009362:Neoplasm Metastasis; D009392:Nephrectomy / Q000379:methods; D015996:Survival Rate
chemical_list: D043169:Endostatins