Ion transport in tumors under electrochemical treatment:: In vivo, in vitro and in silico modeling

Ion transport in tumors under electrochemical treatment:: In vivo, in vitro and in silico modeling
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DOI:
10.1016/j.bioelechem.2007.07.001
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发表时间:
2007-11-01
影响因子:
5
通讯作者:
Turjanski, P.
Turjanski, P.
中科院分区:
化学2区
文献类型:
--
作者:
Colombo, L.;Gonzalez, G.;Turjanski, P.

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癌症的电化学治疗包括将直流电通过插入肿瘤组织局部的两个或多个电极。引起的极端pH变化被认为是主要的肿瘤破坏机制。在这里,我们通过一种联合建模方法来研究EChT过程中的离子传输:体内模型是带皮下肿瘤的BALB/c小鼠,体外模型是琼脂和胶原凝胶,硅模型是使用一维Nemst-Planck和泊松方程来模拟四离子电解质中的离子传输。这种组合建模方法表明,在EChT建模下,电极之间的初始条件几乎是中性的pH值演变为极端的阴极碱性和阳极酸性锋面,相互移动,使它们之间可能存在生物pH区域;向外围,pH值衰减到中性值。pH前沿跟踪揭示了一个时间尺度接近t(1/2),扩散控制过程的特征。这些结果可能对EChT的最佳手术条件和剂量计划具有重要意义,特别是在不断变化的EChT pH区域覆盖活跃癌细胞球形盒的方式上。(c) 2007 Elsevier B.V.版权所有
The electrochemical treatment of cancer (EM) consists in the passage of a direct electric current through two or more electrodes inserted locally in the tumor tissue. The extreme pH changes induced have been proposed as the main tumor destruction mechanism. Here, we study ion transport during EChT through a combined modeling methodology: in vivo modeling with BALB/c mice bearing a subcutaneous tumor, in vitro modeling with agar and collagen gels, and in silico modeling using the one-dimensional Nemst-Planck and Poisson equations for ion transport in a four-ion electrolyte. This combined modeling approach reveals that, under EChT modeling, an initial condition with almost neutral pH evolves between electrodes into extreme cathodic alkaline and anodic acidic fronts moving towards each other, leaving the possible existence of a biological pH region between them; towards the periphery, the pH decays to its neutral values. pH front tracking unveils a time scaling close to t(1/2), signature of a diffusion-controlled process. These results could have significant implications in EChT optimal operative conditions and dose planning, in particular, in the way in which the evolving EChT pH region covers the active cancer cells spherical casket. (c) 2007 Elsevier B.V. All rights reserved.