Variations of dose and electrode spacing for rat breast cancer electrochemical treatment

Abstract

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 Â 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 Â 2 Â 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 signi®cant 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 signi®cantly increased with increasing dose. The changes in electrode spacing (3, 5, and 10 mm) did not signi®cantly 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.

Modified Gompertz Equation for Electrotherapy Murine Tumor Growth Kinetics: Predictions and New Hypotheses

“…This result is in contrast with the fact that these two kinetic parameters are constant during all TGK, as we assume in this paper and as reported previously by our group [17] and other authors [1,23]. Additionally, the TV dependence of FDTV indicates that, V i may have important implications in DEC planning, if we take into account the fact that the tumor is more sensitive to DEC than healthy tissue [7][8][9][10][11][12][13][14][15][18][19][20][21], the Steel equation [22], and the results of Smith et al [34].…”

“…It is important to point out that this REG-II is only reported in the field of ET in cancer [9][10][11][12][13][14][15][18][19][20][21].…”

“…At this time interval, necrosis, apoptosis, chronic inflammation, polymorphous nuclear, monocytes, vascular congestion, and the activation of macrophages and T lymphocytes have been observed [7][8][9][10][11][12][13][14][15][18][19][20][21].…”

“…The actual idea behind in vitro and in vivo studies is to treat the tumor and then to observe its evolution, which is not known to priori [7][8][9][10][11][12][13][14][15][18][19][20][21]. However, the existence of V d establishes that fibrosarcoma Sa-37 tumors have a DEC threshold for which the tumor is completely destroyed, as demonstrated experimentally and theoretically for Ehrlich and fibrosarcoma Sa-37 tumors [14,17], in agreement with other studies [9,10,18,21,33]. This is possible if we establish an explicit dependence of V d as a function of the parameters of Equation 7, the host type, and the ET parameters (dosage and exposure time of DEC, electrode array, and times that DEC is repeated).…”

Electrotherapy on Cancer: Experiment and Mathematical Modeling

“…Many different forms of electrical current with respect to frequencies, pulse-shapes and amplitudes have been employed in biomedicine with the aim of remodeling tissues by enhancing or suppressing cell proliferation. One of the scopes is also employment of direct current as an antitumor agent [Cabrales et al, 2001;Ciria et al, 2004;Jarque et al, 2007;Ren et al, 2001;Schaefer et al, 2008;Turler, et al, 2000;Vodovnik et al, 1992;Xin et al, 2004;Yoon et al, 2007].…”