使用溶解于乙碘油中的血管破坏剂CKD-516联合阿霉素进行化疗栓塞：VX2肿瘤模型研究
Chemoembolization with Vascular Disrupting Agent CKD-516 Dissolved in Ethiodized Oil in Combination with Doxorubicin: A VX2 Tumor Model Study.
作者信息
Lee In Joon, Lee Myungsu, Kim Soo Jin, Kim You Kyung, Won Jong Yun, Chung Jin Wook
机构信息
Department of Radiology, National Cancer Center, Goyang-si, Republic of Korea.
Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
出版信息
J Vasc Interv Radiol. 2018 Aug;29(8):1078-1084. doi: 10.1016/j.jvir.2018.03.016. Epub 2018 Jun 15.
PURPOSE
To assess feasibility and efficacy of CKD-516, a vascular disrupting agent, in transarterial chemoembolization in a liver tumor model.
MATERIALS AND METHODS
A VX2 carcinoma strain was implanted in rabbit liver (n = 40) and incubated for 2 weeks. After confirmation of tumor growth using computed tomography, transarterial chemoembolization was performed. CKD-516 was dissolved in ethiodized oil, and animals were allocated to 4 treatment groups (n = 10 in each): group A, ethiodized oil; group B, ethiodized oil/CKD-516; group C, ethiodized oil + doxorubicin; group D, ethiodized oil/CKD-516 + doxorubicin. To assess hepatic damage, serum aspartate transaminase and alanine transaminase levels were measured on day 1, 3, and 7 after delivery. To assess tumor necrosis, animals were euthanized on day 7, and explanted tumors were stained with hematoxylin and eosin and a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. Percentage areas of viable tumors were calculated using digitalized histopathologic specimen images.
RESULTS
Tumor viability rates were 47.1% ± 11.4%, 27.5% ± 13.6%, 14.4% ± 12.5%, and 0.7% ± 1.0% in groups A, B, C, and D (P < .001). Liver enzyme levels were elevated after drug delivery but recovered during follow-up. Significant between-group differences were observed on days 1, 3, and 7 (aspartate transaminase and alanine transaminase: P = .0135 and P = .0134, P = .0390 and P = .0084, and P = .8260 and P = .0440).
CONCLUSIONS
Treatment with a combination of CKD-516 and conventional transarterial chemoembolization showed therapeutic benefit in a liver tumor model.
目的
评估血管破坏剂CKD - 516在肝肿瘤模型经动脉化疗栓塞中的可行性和疗效。
材料与方法
将VX2癌细胞株植入兔肝脏（n = 40），孵育2周。使用计算机断层扫描确认肿瘤生长后，进行经动脉化疗栓塞。将CKD - 516溶解于碘化油中，动物被分为4个治疗组（每组n = 10）：A组，碘化油；B组，碘化油/CKD - 516；C组，碘化油 + 多柔比星；D组，碘化油/CKD - 516 + 多柔比星。为评估肝损伤，在给药后第1、3和7天测量血清天冬氨酸转氨酶和丙氨酸转氨酶水平。为评估肿瘤坏死情况，在第7天对动物实施安乐死，将切除的肿瘤用苏木精和伊红染色，并进行末端脱氧核苷酸转移酶脱氧尿苷三磷酸缺口末端标记检测。使用数字化组织病理学标本图像计算存活肿瘤的面积百分比。
结果
A、B、C和D组的肿瘤存活率分别为47.1% ± 11.4%、27.5% ± 13.6%、14.4% ± 12.5%和0.7% ± 1.0%（P <.001）。给药后肝酶水平升高，但在随访期间恢复。在第1、3和7天观察到组间存在显著差异（天冬氨酸转氨酶和丙氨酸转氨酶：P =.0135和P =.0134，P =.0390和P =.0084，以及P =.8260和P =.0440）。
结论
CKD - 516与传统经动脉化疗栓塞联合治疗在肝肿瘤模型中显示出治疗益处。
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