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非热纳米电消融术对 UV 诱导的小鼠黑素瘤的治疗作用及其对免疫反应的刺激作用。

Non-thermal nanoelectroablation of UV-induced murine melanomas stimulates an immune response.

机构信息

BioElectroMed Corp., Burlingame, CA, USA.

出版信息

Pigment Cell Melanoma Res. 2012 Sep;25(5):618-29. doi: 10.1111/j.1755-148X.2012.01027.x.

Abstract

Non-thermal nanoelectroablation therapy completely ablates UV-induced murine melanomas. C57/BL6-HGF/SF transgenic mice were exposed to UV radiation as pups and began to develop visible melanomas 5-6 months later. We have treated 27 of these melanomas in 14 mice with nanosecond pulsed electric field (nsPEF) therapy delivering 2000 electric pulses each 100 ns long and 30 kV/cm at a rate of 5-7 pulses per second. All nanoelectroablated melanoma tumors began to shrink within a day after treatment and gradually disappeared over a period of 12-29 days. Pyknosis of nuclei was evident within 1 h of nsPEF treatment, and DNA fragmentation as detected by TUNEL staining was evident by 6 h after nsPEF treatment. In a melanoma allograft system, nsPEF treatment was superior to tumor excision at accelerating secondary tumor rejection in immune-competent mice, suggesting enhanced stimulation of a protective immune response by nsPEF-treated melanomas. This is supported by the presence of CD4(+) -T cells within treated tumors as well as within untreated tumors located in mice with other melanomas that had been treated with nanoelectroablation at least 19 days earlier.

摘要

非热纳米电消融疗法可完全消融 UV 诱导的小鼠黑素瘤。C57/BL6-HGF/SF 转基因小鼠在幼崽时期接受 UV 辐射,然后在 5-6 个月后开始出现可见的黑素瘤。我们用纳秒脉冲电场(nsPEF)疗法治疗了 14 只小鼠的 27 个黑素瘤,每个电场施加 2000 个 100ns 长、30kV/cm 的电脉冲,频率为每秒 5-7 个脉冲。所有纳米电消融的黑素瘤肿瘤在治疗后 1 天内开始缩小,在 12-29 天内逐渐消失。nsPEF 治疗后 1 小时内细胞核出现固缩,6 小时后用 TUNEL 染色检测到 DNA 片段化。在黑素瘤同种异体移植系统中,nsPEF 治疗在加速免疫功能正常的小鼠中继发性肿瘤排斥方面优于肿瘤切除术,这表明 nsPEF 处理的黑素瘤增强了保护性免疫反应的刺激。这一点得到了以下事实的支持:在接受治疗的肿瘤中以及在距离用纳米电消融治疗至少 19 天的其他黑素瘤的未治疗肿瘤中均存在 CD4(+) -T 细胞。

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