Bioimaging Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
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.
Hepatol Int. 2017 Sep;11(5):446-451. doi: 10.1007/s12072-017-9811-4. Epub 2017 Jul 18.
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.
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.
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 mm, 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 mm; 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.
Concomitant administration of CKD-516 during RFA can increase the ablation zone of tumors due to its vascular disrupting effect.
CKD-516 是一种新型的血管破坏剂，可阻断肿瘤内的血流。因此，我们假设同时给予 CKD-516 会通过减少热沉效应来增强射频消融 (RFA) 的治疗效果。我们在大鼠原位肝细胞癌 (HCC) 模型中评估了 CKD-516 与 RFA 联合应用的效果。
将大鼠 HCC 细胞 (N1-S1) 植入 Sprague-Dawley (SD) 大鼠的肝叶中。将小鼠随机分为两组：RFA 组和 CKD-RFA 组。在 CKD-RFA 组中，在 RFA 前 2 小时通过腹腔注射给予 CKD-516。在三苯基四唑氯化物染色的标本上测量消融区的大小。进行末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL) 染色以评估消融区内的凋亡/坏死面积。用抗 CD31 抗体进行免疫组织化学染色以评估 CKD-516 对肿瘤血管的影响。
CKD-RFA 组的消融区大小明显大于 RFA 组（243.10 ± 74.39 与 123.30 ± 28.17 mm，p < 0.001）。在 TUNEL 染色中，CKD-RFA 组的凋亡/坏死面积也明显大于 RFA 组（274.44 ± 140.78 与 143.74 ± 90.13 mm；p = 0.006）。用抗 CD31 抗体进行免疫组织化学染色显示，RFA 组中存在开放的肿瘤血管，而 CKD-RFA 组中则可见血管塌陷，表明 CKD-516 具有血管破坏作用。
在 RFA 期间同时给予 CKD-516 可由于其血管破坏作用而增加肿瘤的消融区。
