Effect of irreversible electroporation on cancer cells

R. Sundararajan, Ramya Rajendran, Sajan S. Shahid, D. Santosh, S. Radhakrishnan, K. Priyadarshan, S. Varsha, U. Kumar, R. Ramachandran, K. Sankaranarayanan
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引用次数: 9

Abstract

Cancer remains responsible for several million deaths each year, occurring worldwide. The conventional treatment strategies for cancer cause a plethora of side effects along with an exorbitant treatment cost per sitting. The focus now is on the development of new modalities of treatments which could minimize the side effects and prove to be an affordable treatment option to the patients. Usage of electrical pulses along with drugs - Electrochemotherapy (ECT) is a fast rising option for the treatment of chemo-refractive cancers. This has proven to be more efficient and effective than other existing methods of treatment and there is a growing evidence of research and clinical trials on the same. The major advantage that this mode of treatment offers is the massive reduction in the dosage of drug that is administered, thus significantly reducing the intensity of undesired side effects. The applied electrical pulses can be of two types - that for reversible and irreversible electroporation of cells. While reversible electroporation is primarily used as a means for delivery of molecules into the cell, irreversible electroporation is a mode which could be applied as such in the absence of a chemodrug to kill the cancerous cells. This would be of immense significance in the clinical scenario since it could be targeted treatment while totally eliminating the necessity of any chemodrug. In this paper we give a detailed report on the effect of such high voltage pulses on cancer cells. The variables tested out in the pulse parameters used include intensity of electric field applied, pulse duration, number of pulses and time interval between each train. The electric field applied is varied between 500V/cm to 2500V/cm with a pulse duration ranging from microseconds to milliseconds to keep the energy delivery constant. The effect of the parameters individually and effect of combination of all these parameters on the cells is studied and discussed in this paper. This study could be of clinical relevance in the translation of these findings to application at the patient-level.
不可逆电穿孔对癌细胞的影响
癌症每年仍在全世界造成数百万人死亡。传统的癌症治疗策略会产生过多的副作用,而且每次的治疗费用也很高。现在的重点是开发新的治疗方式,以尽量减少副作用,并证明是患者负担得起的治疗选择。电脉冲与药物的结合使用——电化疗(ECT)是治疗化学屈光性癌症的一种快速发展的选择。事实证明,这种方法比其他现有的治疗方法更有效,而且有越来越多的证据表明,对这种方法进行了研究和临床试验。这种治疗方式的主要优点是大大减少了所施用药物的剂量,从而大大减少了不希望出现的副作用的强度。应用的电脉冲可以有两种类型-可逆和不可逆的细胞电穿孔。可逆电穿孔主要用于将分子传递到细胞中,而不可逆电穿孔是一种可以在没有化学药物杀死癌细胞的情况下应用的模式。这将在临床场景中具有巨大的意义,因为它可以作为靶向治疗,同时完全消除任何化疗药物的必要性。在本文中,我们详细报道了这种高压脉冲对癌细胞的影响。在脉冲参数中测试的变量包括施加的电场强度、脉冲持续时间、脉冲数和每列之间的时间间隔。施加的电场在500V/cm到2500V/cm之间变化,脉冲持续时间从微秒到毫秒不等,以保持能量传递恒定。本文研究和讨论了各参数的单独作用和各参数的组合作用对细胞的影响。本研究可能具有临床相关性,将这些发现转化为患者水平的应用。
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