Ren R L, Vora N, Yang F, Longmate J, Wang W, Sun H, Li J R, Weiss L, Staud C, McDougall J A, Chou C K
Department of Radiation Research, City of Hope National Medical Center, Duarte, California, USA.
Bioelectromagnetics. 2001 Apr;22(3):205-11. doi: 10.1002/bem.40.
Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P </= 0.001). Electrodes spacing was not an important factor within a given range. At 5, 10, and 15 mm spacing, the fraction showing the necrosis were 54.1, 60.4, and 59.2%, respectively (P = 0.552). The overlap rate of necroses was similar in the 5 and 10 mm groups (82.5 and 85%) and lower in the 15 mm group (65%). We conclude that the tumor responses to EChT, local control, survival rates, and necrosis percentages were significantly increased with increasing dose. The changes in electrode spacing (3, 5, and 10 mm) did not significantly affect the tumor responses to EChT within the same dose. For a diameter of 2.0-2.5 cm rat breast cancer, EChT should be applied with 5-10 mm spacing and a minimum dosage of 80 C.
通过植入电极输送直流电的电化学疗法（EChT）已用于人体实体瘤的局部控制。本研究检验了大鼠乳腺癌对EChT的反应取决于电极间距和剂量这一假设，并探索了用EChT治疗乳腺癌的合适参数。通过向Fisher 344雌性大鼠的右乳腺脂肪垫注射1×10⁶个MTF - 7细胞引发大鼠乳腺癌。当肿瘤长到约2×2×2厘米时，将大鼠随机分为指定的实验组。130只大鼠用于生存研究，129只用于病理学研究。使用一台4通道EChT机器给予电量剂量。生存研究表明，40库仑（C）和60 C组的局部肿瘤控制率低于40%，80和100 C组高于70%。66只大鼠死于原发性肿瘤，包括对照组的所有10只大鼠。一旦大鼠的原发性肿瘤得到控制，未发现复发。处死无原发性肿瘤大鼠（51只）的主要原因是淋巴结转移。13只无肿瘤大鼠存活超过6个月。病理学研究表明EChT诱导的肿瘤坏死有显著的剂量效应。在10、20、40和80 C时，出现坏死的比例分别为39.7%、52.3%、62%和77.7%（P≤0.001）。在给定范围内，电极间距不是一个重要因素。在5、10和15毫米间距时，出现坏死的比例分别为54.1%、60.4%和59.2%（P = 0.552）。5毫米和10毫米组坏死的重叠率相似（82.5%和85%），15毫米组较低（65%）。我们得出结论，随着剂量增加，肿瘤对EChT的反应、局部控制、生存率和坏死百分比显著增加。在相同剂量下，电极间距（3、5和10毫米）的变化对肿瘤对EChT的反应没有显著影响。对于直径为2.0 - 2.5厘米的大鼠乳腺癌，应采用5 - 10毫米的间距和至少80 C的剂量进行EChT治疗。
