Luis Enrique Bergues Cabrales

Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

BackgroundIn vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings.MethodsBALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 106 and 1 × 105 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm3, four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm3 (27.0 C in 0.35 cm3) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm3, two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis.ResultsSignificant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm3, respectively.Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory response, and a moderate peritumoral monocyte infiltration. The morphologic pattern of necrotic cell mass after direct electric current treatment is the coagulative necrosis. These findings were not observed in any of the untreated tumors.ConclusionThe data presented indicate that electrotherapy with low-level DEC is feasible and effective in the treatment of the Ehrlich and fibrosarcoma Sa-37 tumors. Our results demonstrate that the sensitivity of these tumors to direct electric current and survival rates of the mice depended on both the amount of electrical charge and the type of tumor. Also the complete regression of each type of tumor is obtained for a threshold amount of electrical charge.

Antitumor effects of electrochemical treatment

Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas. This treatment is noted for its great effectiveness, minimal invasiveness and local effect. Several studies have been conducted worldwide to evaluate the antitumoral effect of this therapy. In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained. By this reason, researchers have suggested various mechanisms to explain how direct electric current destroys tumor cells. Although, it is generally accepted this treatment induces electrolysis, electroosmosis and electroporation in tumoral tissues. However, action mechanism of this alternative modality on the tumor tissue is not well understood. Although the principle of Electrochemical treatment is simple, a standardized method is not yet available. The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process. The present work analyzes the latest and most important research done on the electrochemical treatment of tumors. We conclude with our point of view about the destruction mechanism features of this alternative therapy. Also, we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy. In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done. Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.

Analytical and numerical solutions of the potential and electric field generated by different electrode arrays in a tumor tissue under electrotherapy

BackgroundElectrotherapy is a relatively well established and efficient method of tumor treatment. In this paper we focus on analytical and numerical calculations of the potential and electric field distributions inside a tumor tissue in a two-dimensional model (2D-model) generated by means of electrode arrays with shapes of different conic sections (ellipse, parabola and hyperbola).MethodsAnalytical calculations of the potential and electric field distributions based on 2D-models for different electrode arrays are performed by solving the Laplace equation, meanwhile the numerical solution is solved by means of finite element method in two dimensions.ResultsBoth analytical and numerical solutions reveal significant differences between the electric field distributions generated by electrode arrays with shapes of circle and different conic sections (elliptic, parabolic and hyperbolic). Electrode arrays with circular, elliptical and hyperbolic shapes have the advantage of concentrating the electric field lines in the tumor.ConclusionThe mathematical approach presented in this study provides a useful tool for the design of electrode arrays with different shapes of conic sections by means of the use of the unifying principle. At the same time, we verify the good correspondence between the analytical and numerical solutions for the potential and electric field distributions generated by the electrode array with different conic sections.

Distributions of the potential and electric field of an electrode elliptic array used in tumor electrotherapy: Analytical and numerical solutions

To estimate the potential and electric field generated by any electrode array is very useful in effective tumor destruction. At present, an electrode array that takes into account the ellipsoidal geometry of the solid tumors has not been proposed. We present both analytical and numerical solutions for the potential and electric field in a solid tumor established by an electrode array with elliptic shape which may be used in vitro, in vivo and in clinical studies for cancer treatment with electrotherapy. These analytical and numerical solutions are obtained using multipole expansion and the finite difference method. Distributions of potential and electric field magnitudes are computed in function of the eccentricity of an elliptical array and compared with those obtained with a circular array of electrode. Maximum difference and Root Means Square Error are used to compare the distributions of the potential and electric field in leading-order and first-order correction and between the analytical and numerical solutions. The results show a good agreement between these distributions in both orders and the analytical and numerical solutions. It was concluded that the mathematical approach presented in this study is a tool for a rapid design of electrode elliptical arrays in order to induce the maximum destruction of the tumor. Moreover, it is shown that, for all values of eccentricity, there is a good correspondence between the distributions of the potential and the electric field for leading-order and first-order correction and for both the analytical and numerical solutions.

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

BackgroundElectrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease.MethodsThe complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumors natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type.ResultsThe first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced.ConclusionThe modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice.

Electric current density distribution in planar solid tumor and its surrounding healthy tissue generated by an electrode elliptic array used in electrotherapy

The knowledge of the electric current density distribution generated by an electrode array is very useful in electrotherapy for tumor treatment. We propose an innovative mathematical approach that takes into account planar solid tumor elliptic geometry, electrical differences between it and its surrounding healthy tissue, and positioning of the electrodes with respect to tumor-surrounding healthy tissue interface. We show the distributions of the electric current density in leading order and first correction terms in a heterogeneous planar medium formed by two regions (tumor and its surrounding healthy tissue) in function of these parameters. The results show that when electrodes are completely inserted in tumor and/or its conductivity is higher than that of its surrounding healthy tissue, the electric current density lines concentrate more in tumor and its tumor-surrounding healthy tissue interface. No significant differences are reported between the electric current density distributions in leading-order and first-order correction for each parameter investigated. However, norm of this physical magnitude reveals that these distributions are different when the ratio between radius of the electrodes and radius of the tumor is less than 0.8. We conclude that the analytical modeling presented in this study is of practical interest because it provides a convenient way to visualize the electric current density distributions generated by an electrode elliptic array in order to efficiently destroy the localized planar tumors with the minimum damage to organism, through an increase of the potential applied to the electrodes, the tumor conductivity with respect to its surrounding healthy tissue and insertion of all electrodes into tumor.

ELF MAGNETIC FIELD EFFECTS ON SOME HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS OF PERIPHERAL BLOOD IN MICE

In this work we have studied some hematological and biochemical parameters of peripheral blood, as well as some histological aspects of liver and spleen during chronic exposure (1, 6, and 8 months) to extremely low-frequency magnetic fields (ELF-MF). Balb/C mice were exposed to an experimental sinusoidal magnetic wavefield of 60 Hz with a 0.11-mT intensity, generated in a system of Helmholtz coils. The results have shown no ELF-MF–cancer relationship during our experimental exposure time. However, leukopenia, hemoglobin decrease, and liver and spleen weight increase were observed. The bioeffects described could be correlated with spleen hyperfunction, which could have been produced by chronic exposure to this ELF-MF.

Is cancer a pure growth curve or does it follow a kinetics of dynamical structural transformation

BackgroundUnperturbed tumor growth kinetics is one of the more studied cancer topics; however, it is poorly understood. Mathematical modeling is a useful tool to elucidate new mechanisms involved in tumor growth kinetics, which can be relevant to understand cancer genesis and select the most suitable treatment.MethodsThe classical Kolmogorov-Johnson-Mehl-Avrami as well as the modified Kolmogorov-Johnson-Mehl-Avrami models to describe unperturbed fibrosarcoma Sa-37 tumor growth are used and compared with the Gompertz modified and Logistic models. Viable tumor cells (1×105) are inoculated to 28 BALB/c male mice.ResultsModified Gompertz, Logistic, Kolmogorov-Johnson-Mehl-Avrami classical and modified Kolmogorov-Johnson-Mehl-Avrami models fit well to the experimental data and agree with one another. A jump in the time behaviors of the instantaneous slopes of classical and modified Kolmogorov-Johnson-Mehl-Avrami models and high values of these instantaneous slopes at very early stages of tumor growth kinetics are observed.ConclusionsThe modified Kolmogorov-Johnson-Mehl-Avrami equation can be used to describe unperturbed fibrosarcoma Sa-37 tumor growth. It reveals that diffusion-controlled nucleation/growth and impingement mechanisms are involved in tumor growth kinetics. On the other hand, tumor development kinetics reveals dynamical structural transformations rather than a pure growth curve. Tumor fractal property prevails during entire TGK.

Integrated analysis of the potential, electric field, temperature, pH and tissue damage generated by different electrode arrays in a tumor under electrochemical treatment

Fil: Soba, Alejandro. Comision Nacional de Energia Atomica; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

Dose-response study for the highly aggressive and metastatic primary F3II mammary carcinoma under direct current: Direct Current on Highly Aggressive Primary Tumors

Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumors long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. 39:460-475, 2018.