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| 兔胰腺移植瘤纳米刀、冷冻、射频的对比研究 |
| 宁周雨1,王鹏1,陈颢1,解婧1,林钧华1,朱晓燕1,陈其文1,徐立涛1,宋利斌1,高嵩1,姜峰2,孟志强1* |
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(1. 复旦大学附属肿瘤医院中西医结合科, 上海 200032;
2. 潍坊诸城中医医院肿瘤科, 潍坊 262200
*通信作者) |
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| 摘要: |
| 目的 通过研究胰腺移植瘤不可逆电穿孔(irreversible electroporation,IRE,俗称"纳米刀")、冷冻、射频术后的肿瘤凋亡、机体免疫反应及血管生成因子情况,观察不同微创技术对胰腺移植瘤的抗肿瘤效果。 方法 兔胰腺移植瘤模型8只,并随机分为模型对照组、纳米刀治疗组、冷冻治疗组及射频治疗组,每组2只。动态观察治疗过程中新西兰大白兔的生命体征,于治疗后第1天全部处死,分离血浆及血清进行检测,H-E染色观察移植瘤组织形态学改变,免疫组织化学方法检测Bcl-2、HSP70和VEGF在胰腺癌移植瘤中的表达,Tunnel 法检测细胞凋亡。 结果 各组实验兔术后均存活。肉眼观肿瘤边界清晰,触之质地较硬,各组治疗区域可见明显凝固性坏死改变。H-E染色显示治疗组坏死区域和正常区域边界清晰,以纳米刀组为著。各组坏死边缘区可见大量红细胞以及炎症细胞浸润,冷冻及射频术区仍可见部分存活细胞。Tunnel结果显示,射频治疗可以明显增加胰腺癌细胞凋亡。与模型对照组相比,各治疗组血浆的Caspase-3、TNF-α及VEGF水平升高;术区Bcl-2及VEGF因子表达降低,HSP70表达升高。术后血清学检测结果显示仅纳米刀治疗后新西兰大白兔的肌酸激酶水平升高,冷冻及射频组未见升高;肌钙蛋白、肝肾功能及血清淀粉酶未见异常。 结论 纳米刀、冷冻、射频治疗兔胰腺移植瘤时,均可能通过诱导细胞凋亡、产生特异的抗肿瘤免疫效应及抑制血管生成来抑制兔胰腺移植瘤的生长,且治疗方法安全、有效。纳米刀在激发机体肿瘤免疫和保护周围重要脏器上有一定的优势。 |
| 关键词: 胰腺肿瘤 异种移植 纳米刀 冷冻消融 射频消融 细胞凋亡 肿瘤免疫 安全性 |
| DOI：10.16781/j.0258-879x.2016.01.0010 |
| 投稿时间：2015-10-23修订日期：2016-01-03 |
| 基金项目: |
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| A comparative study of nanoknife, cryoablation, and radiofrequency ablation for treatment of pancreatic cancer xenograft in rabbits |
| NING Zhou-yu1,WANG Peng1,CHEN Hao1,XIE Jing1,LIN Jun-hua1,ZHU Xiao-yan1,CHEN Qi-wen1,XU Li-tao1,SONG Li-bin1,GAO Song1,JIANG Feng2,MENG Zhi-qiang1* |
(1. Department of Integrative Cancer, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
2. Department of Oncology, Weifang Zhucheng Traditional Chinese Medicine Hospital, Weifang 262200, Shandong, China
*Corresponding author.) |
| Abstract: |
| Objective To investigate the apoptosis, immunity response and angiogenesis factor changes in rabbits with pancreatic cancer xenografts after treatment with irreversible electroporation (IRE,commonly known as nanoknife), cryoablation, or radiofrequency ablation (RFA), and to observe the antitumor effects of the above minimally invasive techniques for pancreatic cancer xenografts. Methods Eight pancreatic cancer xenograft model rabbits were randomly divided into the control, IRE, cryoablation, and RFA groups, with each group containing 2 rabbits. The vital signs of the animals were observed during the treatment and all the rabbits were executed on the next day after treatment. The serum samples were collected to examine the liver, kidney function and creatine kinase levels; and ELISA method was used to detect the cardiac troponin I(CTnI), Caspase-3, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor(VEGF) levels in the plasma. Morphological changes of the tumor tissues were subjected to H-E staining, and Tunnel assay was used to detect the apoptosis of tumor cells. Immunohistochemistry method was applied to detect Bcl-2, HSP70 and VEGF expression in pancreatic cancer xenograft tissues. Results All the rabbits survived after treatment. The tumors had a clear border and were hard in texture. Obvious coagulative necrosis areas were seen in the treatment areas in each treatment group. H-E staining showed a clear borderline between the necrotic and normal areas, which was especially true in the IRE group. A large number of red blood cells and inflammatory cell infiltration were seen around the border of the necrosis in each group, with some live cells seen in the cryoablation and RFA groups. Tunnel assay showed that RFA significantly increased the apoptosis in pancreatic cancer cells compared with the other two treatment groups. The plasma Caspase-3,TNF-α and VEGF levels were increased in each treatment group. Bcl-2 and VEGF expression was decreased and HSP70 expression was increased in the treatment areas. Post-treatment serological test showed that serum amylase, liver, kidney functions and CTnI were all within the normal range, except for a significantly higher level of creatine kinase in the IRE group. Conclusion IRE, cryoablation, and RFA can inhibit pancreatic cancer xenograft through inducing apoptosis, producing specific antitumor immune response and inhibiting angiogenesis; they are safe and effective. IRE has certain advantages in producing specific antitumor immune response and protecting important peripheral organs. |
| Key words: pancreatic neoplasms xenografts nano knife cryoablation radiofrequency ablation apoptosis tumor immunity security |
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