Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma.
Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma.
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DOI：
10.1158/0008-5472.can-09-3067
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发表时间：
2010-02-15
期刊：
影响因子：
11.2
通讯作者：
Larson AC
中科院分区：
文献类型：
--
作者：
Guo Y;Zhang Y;Klein R;Nijm GM;Sahakian AV;Omary RA;Yang GY;Larson AC
不可逆电穿孔 (IRE) 是一种创新的局部区域疗法，涉及传递强电脉冲以诱导纳米级细胞膜缺陷以进行组织消融。本研究的目的是探讨在 N1-S1 啮齿动物模型中使用不可逆电穿孔作为肝脏定向消融技术治疗肝细胞癌 (HCC) 的可行性。 N1-S1大鼠肝癌在30只Sprague-Dawley大鼠体内生长；这些动物被分为治疗组和对照组。对于治疗组，插入IRE电极并施加8 100 µs 2500V脉冲来消融目标肿瘤组织。对于治疗组和对照组（6 只大鼠/组），在基线和 15 天随访间隔进行 MRI 扫描，以测量肿瘤大小（1D 最大直径 Dmax 和估计的 2D 横截面积 Cmax），从而根据观察到的大小变化确定纵向结果。治疗后每隔 1 天、3 天和 7 天处死其他组的治疗动物，以进行治疗反应的病理学评估。 MR 图像显示治疗后 15 天内肿瘤大小显着减小（与未治疗肿瘤的 110±35% Dmax 和 286±125% Cmax 增加相比，Dmax 减少了 32±31% 和 Cmax 减少了 52±39%）。病理学相关研究显示，治疗后 7-15 天，10 只接受治疗的大鼠中有 9 只从治疗前分化差的活 HCC 组织明显进展到广泛的肿瘤坏死和完全消退。我们的研究结果表明，IRE 可有效靶向消融 N1-S1 啮齿动物模型中的肝脏肿瘤； IRE 可能为肝脏定向治疗 HCC 提供一种有前景的新方法。
Irreversible electroporation (IRE) is an innovative local-regional therapy that involves delivery of intense electrical pulses to induce nano-scale cell membrane defects for tissue ablation. The purpose of this study was to investigate the feasibility of using irreversible electroporation as a liver-directed ablation technique for the treatment of hepatocellular carcinoma (HCC) in the N1-S1 rodent model. N1-S1 rat hepatoma was grown in 30 Sprague-Dawley rats; these animals were divided into treatment and control groups. For treatment groups, IRE electrodes were inserted and 8 100 µs 2500V pulses applied to ablate the targeted tumor tissues. For both treatment and control groups (6 rats/group), MRI scans were performed at base-line and 15-day follow-up intervals to measure tumor sizes (1D maximum diameter, Dmax, and estimated 2D cross-sectional area, Cmax) to determine longitudinal outcomes based upon observed size changes. Additional groups of treated animals were sacrificed at 1, 3, and 7-day intervals post-therapy for pathology assessment of treatment response. MR images demonstrated significant tumor size reductions within 15 days post-therapy (32±31% Dmax and 52±39% Cmax decreases compared to 110±35% Dmax and 286±125% Cmax increases for untreated tumors). Pathology correlation studies showed a clear progression from poorly differentiated viable HCC tissues pre-therapy to extensive tumor necrosis and complete regression in 9 out of 10 treated rats 7–15 days after treatment. Our findings suggest that IRE was effective for targeted ablation of liver tumors in the N1-S1 rodent model; IRE may offer a promising new approach for liver-directed treatment of HCC.