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不可逆电穿孔疗法在肝脏中的应用:在大鼠肝细胞癌模型中的纵向疗效研究。

Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma.

机构信息

Department of Radiology, Northwestern University, Chicago, Illinois 60611, USA.

出版信息

Cancer Res. 2010 Feb 15;70(4):1555-63. doi: 10.1158/0008-5472.CAN-09-3067. Epub 2010 Feb 2.

Abstract

Irreversible electroporation (IRE) is an innovative local-regional therapy that involves delivery of intense electrical pulses to tissue to induce nanoscale cell membrane defects for tissue ablation. The purpose of this study was to investigate the feasibility of using IRE as a liver-directed ablation technique for the treatment of hepatocellular carcinoma (HCC). In the N1-S1 rodent model, hepatomas were grown in 30 Sprague-Dawley rats that were divided into treatment and control groups. For treatment groups, IRE electrodes were inserted and eight 100-mus 2,500-V pulses were applied to ablate the targeted tumor tissues. For both groups, magnetic resonance imaging scans were performed at baseline and 15-day follow-up intervals to determine tumor sizes (one-dimensional maximum diameter, D(max); estimated two-dimensional cross-sectional area, C(max)) as a tactic to assess longitudinal outcomes. Additional groups of treated animals were sacrificed at 1-, 3-, and 7-day intervals posttherapy for pathology assessment of treatment response. Magnetic resonance images showed significant tumor size reductions within 15 days posttherapy (32 +/- 31% D(max) and 52 +/- 39% C(max) decreases compared with 110 +/- 35% D(max) and 286 +/- 125% C(max) increases for untreated tumors). Pathology correlation studies documented progression from poorly differentiated viable HCC tissues before treatment to extensive tumor necrosis and full regression in 9 of 10 treated rats 7 to 15 days after treatment. Our findings suggest that IRE can be an effective strategy for targeted ablation of liver tumors, prompting its further evaluation for HCC therapy.

摘要

不可逆电穿孔 (IRE) 是一种创新的局部区域治疗方法,涉及向组织输送高强度电脉冲以诱导纳米级细胞膜缺陷以进行组织消融。本研究旨在探讨 IRE 作为治疗肝细胞癌 (HCC) 的肝定向消融技术的可行性。在 N1-S1 啮齿动物模型中,在 30 只 Sprague-Dawley 大鼠中生长肝癌,将其分为治疗组和对照组。对于治疗组,插入 IRE 电极并施加八个 100-mus 2,500-V 脉冲以消融靶向肿瘤组织。对于两组,在基线和 15 天随访间隔进行磁共振成像扫描,以确定肿瘤大小(一维最大直径,D(max);估计二维横截面积,C(max)),作为评估纵向结果的策略。治疗后 1、3 和 7 天间隔处死另外几组治疗动物,以评估治疗反应的病理。磁共振图像显示治疗后 15 天内肿瘤大小显著缩小(与未治疗肿瘤的 110 +/- 35% D(max)和 286 +/- 125% C(max)增加相比,D(max)减少 32 +/- 31%,C(max)减少 52 +/- 39%)。病理学相关性研究记录了从治疗前低分化存活 HCC 组织进展为治疗后 7 至 15 天 10 只治疗大鼠中的 9 只广泛肿瘤坏死和完全消退。我们的发现表明,IRE 可能是靶向消融肝肿瘤的有效策略,值得进一步评估用于 HCC 治疗。

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