Maraelys Morales González

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.

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.

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.

Original article: Influence of electrode array parameters used in electrotherapy on tumor growth kinetics: A mathematical simulation

Evaluation of the distance between the electrodes, voltage applied to them, and number of electrodes in tumor growth kinetics is very useful for effective tumor destruction when electrotherapy is used. However, a study of this type has not yet been proposed. The aim of this paper is to simulate the influence of such parameters and the point-point electrode configuration on the tumor growth kinetics through a Modified Gompertz Equation. The results show a good agreement between the simulations performed in this study and the experimental results reported by our group and other authors. A critical distance between electrodes and a threshold ratio between the applied electric field and that distributed in the tumor are revealed, for which higher electrotherapy antitumor effectiveness is reached. In conclusion, electrotherapy antitumor effectiveness not only depends on the distance between the electrodes, voltage applied to them, and number of electrodes, but also on the ratio between the applied electric field and that distributed in the tumor. In addition, the results of these simulations may be used to help physicians choose the most appropriate treatment for patients with malignant solid tumors, as we have implemented in a current clinical trial.

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.