Non-thermal nanoelectroablation of UV-induced murine melanomas stimulates an immune response.
Non-thermal nanoelectroablation of UV-induced murine melanomas stimulates an immune response.
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DOI：
10.1111/j.1755-148x.2012.01027.x
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发表时间：
2012-09
影响因子：
4.3
通讯作者：
De Fabo EC
中科院分区：
文献类型：
--
作者：
Nuccitelli R;Tran K;Lui K;Huynh J;Athos B;Kreis M;Nuccitelli P;De Fabo EC
非热纳米电消融疗法完全消融紫外线诱导的小鼠黑色素瘤。C57/BL6-HGF/SF转基因小鼠在幼年接受紫外线照射，5-6个月后开始出现可见的黑色素瘤。我们已经用纳秒脉冲电场(NsPEF)疗法治疗了14只小鼠中的27例黑色素瘤，该疗法提供2000个电脉冲，每个电脉冲长100 ns，以每秒5-7个脉冲的速度传输30千伏/厘米。所有经纳米电消融的黑色素瘤在治疗后一天内开始缩小，并在12-29天内逐渐消失。NsPEF处理后1h，细胞核明显固缩，6h后，TUNEL染色可见明显的DNA片段化。在黑色素瘤同种异体移植系统中，nsPEF治疗在加速免疫活性小鼠的继发性肿瘤排斥反应方面优于肿瘤切除，这表明nsPEF治疗的黑色素瘤增强了保护性免疫反应的刺激。这一点得到了在已治疗的肿瘤中以及在患有其他黑色素瘤的小鼠中存在的CD4+-T细胞的支持，这些黑色素瘤至少在19天前已经接受了纳米电消融治疗。
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.