Study On Biophysical Mechanisms And Tumor State Monitoring Method In Tumor Treatment With Intermediate-frequency Low-intensity Electric Fields

In a certain range,the intermediate-frequency(100?300 kHz)and low-intensity(1?3 V/cm)sinusoidal electric fields have been found to inhibit the proliferation of many different types of tumor cell,and then named them tumor treating fields(TTFields).Although many in vitro cell experiments and animal experiments have confirmed that TTFields can slow or even inhibit tumor growth completely,there are still two related problems that have not been effectively solved.One of them is that the biophysical mechanisms of the inhibition effect on the tumor cell growth caused by the TTFields are not clearly revealed;the other is that there is no simple and effective way for real-time monitoring and evaluation of tumor state in the long-term clinical treatment of glioblastoma multiforme(GBM)tumor with FDA approved TTFields.Due to the unclear treatment mechanism and the failure of real-time monitoring of tumor state,skepticisms about the efficacy of TTFields are arisen by some researchers and doctors,which limits the development of TTFields.So far,most of the studies on TTFields focused on the macroscopic inhibition effect on tumor cell growth under TTFields treatment,but few studies on the mechanisms of TTFields on the sub-cellular level,and studies on the real-time monitoring method of tumor state in GBM tumor treatment are even rarer.Regarding the above problems,this thesis studied the biophysical mechanisms of intermediate-frequency and low-intensity electric fields and the monitoring method of tumor state in tumor therapy.Firstly,the proliferation of HeLa tumor cells under different intermediate-frequency and low-intensity electric fields was analyzed experimentally.Secondly,the electric field and thermal field distribution in the single cell exposed to TTFields is analyzed theoretically and simulated.Then,based on the simulation calculation and cell experiment,the mechanisms of inhibiting tumor cell proliferation by TTFields on the sub-cellular level are studied and analyzed.Finally,we investigated the correlation between tumor state and electrical impedance change,the real-time monitoring method of tumor state of cells in vitro and GBM in vivo based on the change of electrical impedance is proposed,and the simulation and experimental research are carried out?In this thesis,the inhibitory effect of TTFields on tumor cell proliferation was verified by HeLa cell experiment,and the effects of different electric field conditions such as electric field intensity,frequency and waveform on the inhibitory effect were compared and analyzed.In the simulation study,the single cell regular and irregular models of normal and tumor cells were established,and the electric field and temperature field in the cell were analyzed and compared under different cell division conditions,electric field conditions and cell parameters.Based on the experimental and simulation results,the thermal effect,force effect and micro-environmental distortion effect of TTFields on tumor cells were analyzed,and showed less support to the thermal damage effect of electric field and the force damage mechanism on microtubule,chromosome,organelle and other secondary cell structures in cells,and revealed a novel mechanism that the change of membrane potential induced by electric field affects the concentration of Ca²⁺and leads to the inhibition of abnormal cell division.Finally,in order to solve the problem of tracking and monitoring the tumor state in GBM treatment,the multi-function of treatment electrode is proposed,and the method of evaluating the size of intracranial tumor by measuring the change of electrical impedance between electrodes is explored and analyzed,which proves the potential application value of this method.