Su Jung Ham1,2, YoonSeok Choi3,4, Seul-I Lee1,2, Jinil Kim1,2, Young Il Kim4, Jin Wook Chung4, Kyung Won Kim5,6. 1. Bioimaging Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. 2. Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea. 3. Biomedical Translational Research Center, GangNeung Asan Medical Center, Sacheon-myoen, Bangdong-kil 38, GangNeung, Gangwon, 210-711, Korea. 4. Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. 5. Bioimaging Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. kyungwon_kim@amc.seoul.kr. 6. Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea. kyungwon_kim@amc.seoul.kr.
Abstract
BACKGROUND: CKD-516 is a novel vascular disrupting agent that shuts down intratumoral blood flow. We therefore hypothesized that concomitant administration of CKD-516 would enhance the therapeutic efficacy of radiofrequency ablation (RFA) by reducing heat sink effects. We assessed the effects of the combination of CKD-516 and RFA in a rat orthotopic hepatocellular carcinoma (HCC) model. METHODS: Rat HCC cells (N1-S1) were engrafted into the hepatic lobe of Sprague-Dawley (SD) rats. Mice were randomly divided into two groups: RFA-only and CKD-RFA. In the CKD-RFA group, CKD-516 was administered by intraperitoneal injection 2 h before RFA. Ablation zone size was measured on triphenyltetrazolium chloride-stained specimens. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to evaluate the area of apoptosis/necrosis in the ablation zone. Immunohistochemistry with anti-CD31 antibody was performed to evaluate the effect of CKD-516 on tumor vessels. RESULTS: Ablation zone size was significantly larger in the CKD-RFA group than in the RFA-only group (243.10 ± 74.39 versus 123.30 ± 28.17 mm2, p < 0.001). On TUNEL staining, the area of apoptosis/necrosis was also significantly larger in the CKD-RFA group than in the RFA-only group (274.44 ± 140.78 versus 143.74 ± 90.13 mm2; p = 0.006). Immunohistochemistry with anti-CD31 antibody revealed patent tumor vessels in the RFA-only group, while collapsed vessels were seen in the CKD-RFA group, indicating a vascular shutdown effect of CKD-516. CONCLUSION: Concomitant administration of CKD-516 during RFA can increase the ablation zone of tumors due to its vascular disrupting effect.
BACKGROUND: CKD-516 is a novel vascular disrupting agent that shuts down intratumoral blood flow. We therefore hypothesized that concomitant administration of CKD-516 would enhance the therapeutic efficacy of radiofrequency ablation (RFA) by reducing heat sink effects. We assessed the effects of the combination of CKD-516 and RFA in a ratorthotopic hepatocellular carcinoma (HCC) model. METHODS:Rat HCC cells (N1-S1) were engrafted into the hepatic lobe of Sprague-Dawley (SD) rats. Mice were randomly divided into two groups: RFA-only and CKD-RFA. In the CKD-RFA group, CKD-516 was administered by intraperitoneal injection 2 h before RFA. Ablation zone size was measured on triphenyltetrazolium chloride-stained specimens. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to evaluate the area of apoptosis/necrosis in the ablation zone. Immunohistochemistry with anti-CD31 antibody was performed to evaluate the effect of CKD-516 on tumor vessels. RESULTS: Ablation zone size was significantly larger in the CKD-RFA group than in the RFA-only group (243.10 ± 74.39 versus 123.30 ± 28.17 mm2, p < 0.001). On TUNEL staining, the area of apoptosis/necrosis was also significantly larger in the CKD-RFA group than in the RFA-only group (274.44 ± 140.78 versus 143.74 ± 90.13 mm2; p = 0.006). Immunohistochemistry with anti-CD31 antibody revealed patent tumor vessels in the RFA-only group, while collapsed vessels were seen in the CKD-RFA group, indicating a vascular shutdown effect of CKD-516. CONCLUSION: Concomitant administration of CKD-516 during RFA can increase the ablation zone of tumors due to its vascular disrupting effect.
Authors: Chang Hoon Moon; Seung Ju Lee; Ho Yong Lee; Le Thi Kim Dung; Wha Ja Cho; HeeJeong Cha; Jeong Woo Park; Young Joo Min Journal: Invest New Drugs Date: 2013-11-08 Impact factor: 3.850
Authors: S N Goldberg; P F Hahn; K K Tanabe; P R Mueller; W Schima; C A Athanasoulis; C C Compton; L Solbiati; G S Gazelle Journal: J Vasc Interv Radiol Date: 1998 Jan-Feb Impact factor: 3.464
Authors: Young Il Kim; Kyung Won Kim; Han Kyu Lee; Jisuk Park; Jin Wook Chung; Hyewon Youn; Soo Jin Kim; Dal-Hyun Kim; Jen-Chieh Tseng; Jeong Min Lee Journal: Anticancer Res Date: 2014-04 Impact factor: 2.480