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用于癌症治疗的可逆电穿孔

Reversible electroporation for cancer therapy.

作者信息

Shiwani Taha, Singh Dhesi Simran, Wah Tze Min

机构信息

Department of Diagnostic and Interventional Radiology, St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Beckett St, Leeds, LS9 7TF, United Kingdom.

出版信息

Br J Radiol. 2025 Mar 1;98(1167):313-320. doi: 10.1093/bjr/tqae231.

DOI:10.1093/bjr/tqae231
PMID:39579146
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11840168/
Abstract

Reversible electroporation (EP) refers to the use of high-voltage electrical pulses on tissues to increase cell membrane permeability. It allows targeted delivery of high concentrations of chemotherapeutic agents including cisplatin and bleomycin, a process known as electrochemotherapy (ECT). It can also be used to deliver toxic concentrations of calcium and gene therapies that stimulate an anti-tumour immune response. ECT was validated for palliative treatment of cutaneous tumours. Evidence to date shows a mean objective response rate of ∼80% in these patients. Regression of non-treated lesions has also been demonstrated, theorized to be from an in situ vaccination effect. Advances in electrode development have also allowed treatment of deep-seated metastatic lesions and primary tumours, with safety demonstrated in vivo. Calcium EP and combination immunotherapy or immunogene electrotransfer is also feasible, but research is limited. Adverse events of ECT are minimal; however, general anaesthesia is often necessary, and improvements in modelling capabilities and electrode design are required to enable sufficient electrical coverage. International collaboration between preclinical researchers, oncologists, and interventionalists is required to identify the most effective combination therapies, to optimize procedural factors, and to expand use, indications and assessment of reversible EP. Registries with standardized data collection methods may facilitate this.

摘要

可逆性电穿孔(EP)是指对组织施加高压电脉冲以增加细胞膜通透性。它能实现包括顺铂和博来霉素在内的高浓度化疗药物的靶向递送,这一过程称为电化学疗法(ECT)。它还可用于递送有毒浓度的钙以及能激发抗肿瘤免疫反应的基因疗法。ECT已被证实可用于皮肤肿瘤的姑息治疗。迄今为止的证据表明,这些患者的平均客观缓解率约为80%。未经治疗的病灶出现消退也已得到证实,理论上这是由原位疫苗接种效应所致。电极研发的进展也使得深部转移性病灶和原发性肿瘤的治疗成为可能,其安全性已在体内得到证实。钙电穿孔与联合免疫疗法或免疫基因电转染也是可行的,但相关研究有限。ECT的不良事件极少;然而,通常需要全身麻醉,并且需要改进建模能力和电极设计以实现足够的电覆盖范围。临床前研究人员、肿瘤学家和介入专家之间的国际合作对于确定最有效的联合疗法、优化操作因素以及扩大可逆性电穿孔的应用、适应证和评估至关重要。采用标准化数据收集方法的登记系统可能有助于实现这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/1f675525ef32/tqae231f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/e1698ac72992/tqae231f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/ede3ca32f53b/tqae231f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/a4f2c9b5b8b6/tqae231f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/1f675525ef32/tqae231f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/e1698ac72992/tqae231f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/ede3ca32f53b/tqae231f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/a4f2c9b5b8b6/tqae231f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96b1/11840168/1f675525ef32/tqae231f4.jpg

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本文引用的文献

1
Electrochemotherapy combined with immunotherapy - a promising potential in the treatment of cancer.电化学疗法联合免疫疗法——癌症治疗的有前途的潜在手段。
Front Immunol. 2024 Jan 15;14:1336866. doi: 10.3389/fimmu.2023.1336866. eCollection 2023.
2
Optimal Dosing and Patient Selection for Electrochemotherapy in Solid Abdominal Organ and Bone Tumors.腹部实体器官和骨肿瘤电化学疗法的最佳剂量及患者选择
Bioengineering (Basel). 2023 Aug 18;10(8):975. doi: 10.3390/bioengineering10080975.
3
Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation.
肿瘤学中的脉冲电场:第四届电穿孔世界大会当前临床实践与研究方向概览
Cancers (Basel). 2023 Jun 25;15(13):3340. doi: 10.3390/cancers15133340.
4
Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis.电化学疗法与放疗治疗原发性皮肤恶性肿瘤或原发性实体器官恶性肿瘤皮肤转移瘤:系统评价和叙述性综合。
PLoS One. 2023 Jul 13;18(7):e0288251. doi: 10.1371/journal.pone.0288251. eCollection 2023.
5
The effectiveness of calcium electroporation combined with gene electrotransfer of a plasmid encoding IL-12 is tumor type-dependent.钙电穿孔联合基因电转染编码 IL-12 的质粒的疗效与肿瘤类型有关。
Front Immunol. 2023 May 25;14:1189960. doi: 10.3389/fimmu.2023.1189960. eCollection 2023.
6
Endoscopic calcium electroporation for colorectal cancer: a phase I study.内镜下钙电穿孔治疗结直肠癌:一项I期研究。
Endosc Int Open. 2023 May 9;11(5):E451-E459. doi: 10.1055/a-2033-9831. eCollection 2023 May.
7
PIRET-A Platform for Treatment Planning in Electroporation-Based Therapies.PIRET-A 平台用于基于电穿孔疗法的治疗计划。
IEEE Trans Biomed Eng. 2023 Jun;70(6):1902-1910. doi: 10.1109/TBME.2022.3232038. Epub 2023 May 19.
8
Is the association of electrochemotherapy and bone fixation rational in patients with bone metastasis?电化学疗法联合骨固定术在骨转移患者中是否合理?
J Surg Oncol. 2023 Jul;128(1):125-133. doi: 10.1002/jso.27247. Epub 2023 Mar 26.
9
Percutanous Electrochemotherapy (ECT) in Primary and Secondary Liver Malignancies: A Systematic Review.经皮电化学疗法(ECT)治疗原发性和继发性肝脏恶性肿瘤:一项系统评价
Diagnostics (Basel). 2023 Jan 5;13(2):209. doi: 10.3390/diagnostics13020209.
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High-Frequency Nanosecond Bleomycin Electrochemotherapy and its Effects on Changes in the Immune System and Survival.高频纳秒博来霉素电化学疗法及其对免疫系统变化和生存的影响。
Cancers (Basel). 2022 Dec 19;14(24):6254. doi: 10.3390/cancers14246254.