title: Combined Radiofrequency Ablation and Double Anti-Angiogenic Protein Therapy to Increase Coagulation Efficacy: An Experimental Study in a Murine Renal Carcinoma Model.
abstract: OBJECTIVE
  To evaluate whether suppression of tumor microvasculature by double anti-angiogenic protein (DAAP) treatment could increase the extent of radiofrequency ablation (RFA)-induced coagulation in a murine renal cell carcinoma model.
  
  
  METHODS
  Renal cell carcinoma cell lines were implanted subcutaneously into 10 nude mice. Four mice received adenoviral DAAP treatment and 6 mice received sterile 0.9% saline solution as DAAP-untreated group. The effect of DAAP was evaluated according to the vascularity by contrast-enhanced ultrasound (CEUS) using microbubbles. Four DAAP-treated mice and 4 DAAP-untreated mice were then treated with RFA, resulting in 3 groups: no-therapy (n = 2), RFA only (n = 4), and RFA combined with DAAP treatment (n = 4). Immediately after RFA, the size of coagulation necrosis and mitochondrial enzyme activity were compared between the groups using analysis of variance (ANOVA) and post hoc test.
  
  
  RESULTS
  The contrast enhancement ratio for tumor vascularization on CEUS was significantly lower in the DAAP treated group than in DAAP-untreated group (30.2 ± 9.9% vs. 77.4 ± 17.3%; p = 0.021). After RFA, the mean coagulation diameter was 0 mm for no-therapy group, 6.7 ± 0.7 mm for the RFA only group and 8.5 ± 0.4 mm for the RFA with DAAP group (ANOVA, p < 0.001). The area of viable mitochondria within the tumor was 27.9 ± 3.9% in no-therapy group, 10.3 ± 4.5% in the RFA only group, and 2.1 ± 0.7% in the RFA with DAAP group (ANOVA, p < 0.001).
  
  
  CONCLUSIONS
  Our results suggest the potential value of combining RFA with anti-angiogenic therapy.
authors.affiliation: Imaging Science Research Center, Wonkwang University School of Medicine, Iksan 570-711, Korea.
authors.forename: Hong Young
authors.initials: HY
authors.lastname: Jun
authors.affiliation: Imaging Science Research Center, Wonkwang University School of Medicine, Iksan 570-711, Korea.
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Surgery, Wonkwang University School of Medicine, Iksan 570-711, Korea.
authors.forename: Seung Jae
authors.initials: SJ
authors.lastname: Byun
authors.affiliation: Imaging Science Research Center, Wonkwang University School of Medicine, Iksan 570-711, Korea.
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Jeong
authors.affiliation: Imaging Science Research Center, Wonkwang University School of Medicine, Iksan 570-711, Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Radiology, Wonkwang University School of Medicine, Iksan 570-711, Korea.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Imaging Science Research Center, Wonkwang University School of Medicine, Iksan 570-711, Korea. ; Department of Radiology, Wonkwang University School of Medicine, Iksan 570-711, Korea.
authors.forename: Kwon-Ha
authors.initials: KH
authors.lastname: Yoon
mesh_terms: D000256:Adenoviridae; D042501:Angiogenic Proteins / Q000037:antagonists & inhibitors*; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000601:surgery / Q000628:therapy*; D017115:Catheter Ablation / Q000379:methods*; D003131:Combined Modality Therapy; D003287:Contrast Media; D007680:Kidney Neoplasms / Q000098:blood supply / Q000601:surgery / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000601:surgery / Q000628:therapy*; D011994:Recombinant Proteins; D014463:Ultrasonography
chemical_list: D042501:Angiogenic Proteins; D003287:Contrast Media; D011994:Recombinant Proteins
keywords: Angiogenesis; Anti-angiogenic protein; Mice model; Radiofrequency ablation; Renal cell carcinoma