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Combined Radiofrequency Ablation and Double Anti-Angiogenic Protein Therapy to Increase Coagulation Efficacy: An Experimental Study in a Murine Renal Carcinoma Model.

Jun HY, Ryu JH, Byun SJ, Jeong CW, Kim TH, Lee YH, Yoon KH - Korean J Radiol (2015)

Bottom Line: 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.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).Our results suggest the potential value of combining RFA with anti-angiogenic therapy.

View Article: PubMed Central - PubMed

Affiliation: Imaging Science Research Center, Wonkwang University School of Medicine, Iksan 570-711, Korea.

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.

Materials and 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).

Conclusion: Our results suggest the potential value of combining RFA with anti-angiogenic therapy.

No MeSH data available.


Related in: MedlinePlus

Assessment for mitochondrial viable area.Cross sections of three gross pathologic specimens stained with 2,3,5-triphenyl-2H-tetrazolium chloride. Mitochondrial activity is shown in red. Nonviable ablated tumor remains white (arrows). Mitochondrial activity is clearly seen in (A) untreated tumor but not in treated tumor with (B) radiofrequency ablation (RFA) only or with (C) RFA and double anti-angiogenic protein (DAAP). (D-F) Remaining viable mitochondria were overlaid as red color using MATLAB.
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Figure 3: Assessment for mitochondrial viable area.Cross sections of three gross pathologic specimens stained with 2,3,5-triphenyl-2H-tetrazolium chloride. Mitochondrial activity is shown in red. Nonviable ablated tumor remains white (arrows). Mitochondrial activity is clearly seen in (A) untreated tumor but not in treated tumor with (B) radiofrequency ablation (RFA) only or with (C) RFA and double anti-angiogenic protein (DAAP). (D-F) Remaining viable mitochondria were overlaid as red color using MATLAB.

Mentions: Figure 3 showed TTC staining in the 3 groups for assessment of the efficacy of RFA only and RFA combined with DAAP treatment. The mean coagulation diameter (white area) measured 8.5 ± 0.4 mm in RFA combined with DAAP group, 6.7 ± 0.7 mm in RFA only group, and 0 mm in no-therapy group (ANOVA, p < 0.001) (Table 2). Using Matlab analysis, the area of viable mitochondria showed significant difference between the 3 groups (ANOVA, p < 0.001). Figure 4 demonstrated the area of viable mitochondria within the tumor and its averaged values were summarized in Table 2. The area of viable mitochondria within the tumor was significantly smaller in RFA combined with DAAP group, as compared with RFA only group (red area, 2.1 ± 0.7% vs. 10.3 ± 4.5%; p = 0.024) and in RFA only group, as compared with no-therapy group (red area, 10.3 ± 4.5% vs. 27.9 ± 3.9%; p = 0.001).


Combined Radiofrequency Ablation and Double Anti-Angiogenic Protein Therapy to Increase Coagulation Efficacy: An Experimental Study in a Murine Renal Carcinoma Model.

Jun HY, Ryu JH, Byun SJ, Jeong CW, Kim TH, Lee YH, Yoon KH - Korean J Radiol (2015)

Assessment for mitochondrial viable area.Cross sections of three gross pathologic specimens stained with 2,3,5-triphenyl-2H-tetrazolium chloride. Mitochondrial activity is shown in red. Nonviable ablated tumor remains white (arrows). Mitochondrial activity is clearly seen in (A) untreated tumor but not in treated tumor with (B) radiofrequency ablation (RFA) only or with (C) RFA and double anti-angiogenic protein (DAAP). (D-F) Remaining viable mitochondria were overlaid as red color using MATLAB.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499541&req=5

Figure 3: Assessment for mitochondrial viable area.Cross sections of three gross pathologic specimens stained with 2,3,5-triphenyl-2H-tetrazolium chloride. Mitochondrial activity is shown in red. Nonviable ablated tumor remains white (arrows). Mitochondrial activity is clearly seen in (A) untreated tumor but not in treated tumor with (B) radiofrequency ablation (RFA) only or with (C) RFA and double anti-angiogenic protein (DAAP). (D-F) Remaining viable mitochondria were overlaid as red color using MATLAB.
Mentions: Figure 3 showed TTC staining in the 3 groups for assessment of the efficacy of RFA only and RFA combined with DAAP treatment. The mean coagulation diameter (white area) measured 8.5 ± 0.4 mm in RFA combined with DAAP group, 6.7 ± 0.7 mm in RFA only group, and 0 mm in no-therapy group (ANOVA, p < 0.001) (Table 2). Using Matlab analysis, the area of viable mitochondria showed significant difference between the 3 groups (ANOVA, p < 0.001). Figure 4 demonstrated the area of viable mitochondria within the tumor and its averaged values were summarized in Table 2. The area of viable mitochondria within the tumor was significantly smaller in RFA combined with DAAP group, as compared with RFA only group (red area, 2.1 ± 0.7% vs. 10.3 ± 4.5%; p = 0.024) and in RFA only group, as compared with no-therapy group (red area, 10.3 ± 4.5% vs. 27.9 ± 3.9%; p = 0.001).

Bottom Line: 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.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).Our results suggest the potential value of combining RFA with anti-angiogenic therapy.

View Article: PubMed Central - PubMed

Affiliation: Imaging Science Research Center, Wonkwang University School of Medicine, Iksan 570-711, Korea.

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.

Materials and 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).

Conclusion: Our results suggest the potential value of combining RFA with anti-angiogenic therapy.

No MeSH data available.


Related in: MedlinePlus