Studies On Mechanism And Key Technologies For Clinical Application Of IRE Tumor Treatment

Tumor is the recognized public health problem all over the world, which is related to human health and life. However, existing therapies don't work so well considering of the limits of their indications and contraindications as well as side effects. As a new idea of curing tumor, Irreversible electroporation (IRE) has a great advantage compared with the existing physical therapy and shows good clinical application.Therefore, we work hard at the mechanisms of IRE treatment and try to solve the basic problems of key technologies involved when the academic thoughts are to be realized in the clinical application. So, an in-depth research is focused on IRE tumor treatment with the support of the national natural science foundation in key project'Mechanism and key technology researches on IRE tumor treatment of short pulses'(grant No.50637020). The major achievements are as follows:①Researches on mechanism of electroporation in the pulsed electric fields. A model of lipid bilayer containing DPPC was set up. The process of electroporation and its pore size in lipid bilayer was analyzed from the atomic level as well as the mechanism of electroporation formation; the balance equation of the molecular interaction within the cell membrane was constructed to calculate the change process of molecular interaction with the increase of the applied electric intensity.②Researches on mechanism of tumor cells in the pulsed electric fields The electric intensity parameters that induced RE, IRE and apoptosis were analyzed systematically to study the window effect mechanism of the microsecond pulse electric intensity parameters when human cervical cancer HeLa cells were taken as research objects; typical electric pulse parameters were chosen to discuss the tumor cell death process induced by microsecond pulse electric fields and corresponding mechanism; adhesion, invasion and migration abilities of the cells treated by the pulse electric fields have been studied respectively. Accordingly, the effects of the transfer ability of tumor cells treated with microsecond pulses and the possible mechanisms were discussed.③Researches on efficacy and safety of IRE tumor treatment in clinical applications. Liver cancer is taken as the indication of the IRE treatment and tumor-burdened nude mouse as the research objects. It has been confirmed that IRE is an effective method to cure liver cancer by observing the inhibitory curve and survival curves after treatments; the liver tissues of Nanjiang Gazelle were taken as research objects for the application in vivo of the IRE treatment. The feasibility of guiding the treatments and assessing the treatment effects by type-B ultrasonic has been discussed, and it was clarified that the treatment area was controllable, which proved the safety of the method.④Researches on the parameter optimizations of IRE tumor treatment in clinical applications. Based on the electrostatic field distribution theory in combination with the bio-heat transfer theory, we explored the optimal combination of parameters of IRE treatment by the corresponding electric field and temperature field simulations while avoiding thermal effects. That is, the tumor cells were killed when the surrounding normal tissues were little suffered, which offered the references for the choice of the parameters of IRE treatment in clinical applications.⑤Development of IRE treatment prototype. Combined with the high-voltage high-power electronic switches and triggering technology, control technology, a set of IRE tumor treatment device prototype has been developed on the basis of charge-discharge of the capacitor in traditional pulsed power technology. According to the debugging it showed that the prototype is stable and reliable, which is also able to control the output voltage, width, frequency and pulse number of output microsecond square wave pulses accurately.In summary, this paper discussed the mechanism of the irreversible electroporation effect from the point of view of molecular dynamics and put forward the mechanism of irreversible electroporation induced by microsecond pulse electric field on the basic of the cell experiments. Besides, we also solved the key technical problems of effectiveness, safety and feasibility of ultrasound guide, proposed optimization strategy of treatment plan, developed and improved the novel treatment system prototype, which provided the material basis, theoretical basis and technical support for the clinical application of IRE tumor treatment.