Electronic Thesis/Dissertation
 

Thermal and Non-Thermal Atmospheric Plasma in Cancer Treatment

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Thermal atmospheric plasma technologies such as Argon Plasma Coagulation (APC), have been widely used in medicine to coagulate, cut and ablate tissues. The main effect of these plasmas is created through tissue heating. In contrast, the effect of non-thermal plasma, also referred to as Cold Atmospheric Plasma (CAP), is based on a considerable number of highly reactive chemical species without the presence of heat. Thermal and non-thermal plasmas have a wide range of applications in cancer treatment, from endoscopic APC treatment of early gastric cancer to CAP treatment of glioma. In the past two decades, researchers have focused on further exploring and better understanding the interaction of plasma with living cells and tissue. This dissertation offers insight into the APC-tissue interactions and the CAP-cell interactions.This study demonstrates that the dielectric properties of biological tissue play a significant role in how the tissue responds to APC treatment. At the tissue level, the APC technique is well-known for thermal non-contact coagulation, with an ability to provide treatment for less accessible regions, and without damage to the tissue. The amount of power applied is one of the key elements for providing a safe and effective treatment. Our results revealed that in the optimal tissue resistance range of 0.8-3.7 kΩ, the majority of the applied power was delivered to the tissue with a small percentage (20-40%) being consumed by the plasma channel. Our findings suggest that surgeons can safely deliver the accurate amount of power by adjusting the power settings based on the expected resistance of the tissue being treated.Roles of the adaptive properties of CAP, including treatment duration and discharge voltage, in mediating cancer suppression in vitro, is an additional topic explored in this dissertation. A proof-of-principle investigation identified the role of discharge voltage in the adjustment of plasma composition and treatment duration in the modification of overall plasma action. The effect of CAP in two cancer cell lines, glioblastoma and breast cancer, was monitored in real-time by observing cell viability. Apoptosis (programmed cell death) was determined to be the likely mechanism initiating a reduction in viable cells via changes to the mitochondrial membrane potential. The findings reveal compelling evidence in support of the important role played by the adaptive properties of CAP, in mediating cancer suppression. The presented discoveries are significant since they will facilitate the future development of a novel adaptive CAP platform which will rely on cell response data collected in real time. Therefore, the optimization of CAP operational parameters via a novel adaptive CAP platform will be essential in providing long-lasting outcomes in cancer therapy.CAP has also received heightened attention as an alternative therapy due to its ability to impact drug resistant tumors such as gliomas. These tumors have played a significant role in propelling CAP technology to the front lines as a safer alternative compared to more conventional treatment methods such as chemotherapy. This dissertation presents the third investigation of biomedical applications of CAP for sensitizing glioblastoma cells to temozolomide (TMZ). This is also the very first study which explores the role of CAP in cell migration and integrin expression in the presence of TMZ. TMZ concentrations of 10 and 50 uM were evaluated in vitro over the course of days with a plasma treatment of 180 seconds. α6 and αv integrins were considered for their roles in CAP induced cell death, G2/M arrest and decrease in the rate of cell migration. The findings reveal compelling evidence in support of the important role played by CAP in mediating cancer suppression, through direct treatment or by functioning as a drug sensitizing agent.

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