Nuccitelli Richard, Chen Xinhua, Pakhomov Andrei G, Baldwin Wallace H, Sheikh Saleh, Pomicter Jennifer L, Ren Wei, Osgood Christopher, Swanson R James, Kolb Juergen F, Beebe Stephen J, Schoenbach Karl H
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23510, USA.
Int J Cancer. 2009 Jul 15;125(2):438-45. doi: 10.1002/ijc.24345.
We have discovered a new, ultrafast therapy for treating skin cancer that is extremely effective with a total electric field exposure time of only 180 microsec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec) electrical pulses to murine melanomas in vivo triggers both necrosis and apoptosis, resulting in complete tumor remission within an average of 47 days in the 17 animals treated. None of these melanomas recurred during a 4-month period after the initial melanoma had disappeared. These pulses generate small, long-lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting in increased membrane permeability to small molecules and ions, as well as an increase in intracellular Ca(2+), DNA fragmentation, disruption of the tumor's blood supply and the initiation of apoptosis. Apoptosis was indicated by a 3-fold increase in Bad labeling and a 72% decrease in Bcl-2 labeling. In addition, microvessel density within the treated tumors fell by 93%. This new therapy utilizing nanosecond pulsed electric fields has the advantages of highly localized targeting of tumor cells and a total exposure time of only 180 microsec. These pulses penetrate into the interior of every tumor cell and initiate DNA fragmentation and apoptosis while at the same time reducing blood flow to the tumor. This new physical tumor therapy is drug free, highly localized, uses low energy, has no significant side effects and results in very little scarring.
我们发现了一种治疗皮肤癌的全新超快疗法,这种疗法极为有效,总电场暴露时间仅为180微秒。对体内的鼠黑色素瘤施加300个高压(40 kV/cm)、超短(300纳秒)电脉冲,会引发坏死和凋亡,在接受治疗的17只动物中,平均47天内肿瘤完全缓解。在最初的黑色素瘤消失后的4个月期间,这些黑色素瘤均未复发。这些脉冲在暴露细胞的质膜上产生小的、持久的、整流纳米孔,导致膜对小分子和离子的通透性增加,以及细胞内Ca(2+)增加、DNA片段化、肿瘤血液供应中断和凋亡启动。Bad标记增加3倍和Bcl-2标记减少72%表明发生了凋亡。此外,治疗后肿瘤内的微血管密度下降了93%。这种利用纳秒脉冲电场的新疗法具有高度靶向肿瘤细胞和总暴露时间仅180微秒的优点。这些脉冲穿透每个肿瘤细胞内部,引发DNA片段化和凋亡,同时减少肿瘤的血液流动。这种新的物理肿瘤疗法无药物、高度局部化、能量低、无明显副作用且几乎不产生疤痕。