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dc.contributor.authorIvey, Jill Wintersen_US
dc.date.accessioned2017-09-06T08:01:06Z
dc.date.available2017-09-06T08:01:06Z
dc.date.issued2017-09-05en_US
dc.identifier.othervt_gsexam:12574en_US
dc.identifier.urihttp://hdl.handle.net/10919/78806
dc.description.abstractGlioblastoma multiforme (GBM) is the most common and lethal primary brain cancer with an average survival time of 15 months. GBM is considered incurable with even the most aggressive multimodal therapies and is characterized by near universal recurrence. Irreversible electroporation (IRE) is a cellular ablation method currently being investigated as a therapy for a variety of cancers. Application of IRE involves insertion of electrodes into tissue to deliver pulsed electric fields (PEFs), which destabilize the cell membrane past the point of recovery, thereby inducing cell death. While this treatment modality has numerous advantages, the lack of selectivity for malignant cells limits its application in the brain where damage to healthy tissue is especially deleterious. In this dissertation we hypothesize that a form of IRE therapy, high-frequency IRE (H-FIRE), may be able to act as a selective targeted therapy for GBM due to its ability to create an electric field inside a cell to interact with altered inner organelles. Through a comprehensive investigation involving experimental testing combined with numerical modeling, we have attained results in strong support of this hypothesis. Using tissue engineered hydrogels as our platform for therapy testing, we demonstrate selective ablation of GBM cells. We develop mathematical models that predict the majority of the electric field produced by H-FIRE pulses reach the inside of the cell. We demonstrate that the increased nuclear to cytoplasm ratio (NCR) of malignant GBM cells compared to healthy brain—evidenced in vivo and in in vitro tissue mimics—is correlated with greater ablation volumes and thus lower electric field thresholds for cell death when treated with H-FIRE. We enhance the selectivity achieved with H-FIRE using a molecularly targeted drug that induces an increase in NCR. We tune the treatment pulse parameters to increase selective malignant cell killing. Finally, we demonstrate the ability of H-FIRE to ablate therapy-resistant GBM cells which are a focus of many next-generation GBM therapies. We believe the evidence presented in this dissertation represents the beginning stages in the development of H-FIRE as a selective therapy to be used for treatment of human brain cancer.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsThis item is protected by copyright and/or related rights. Some uses of this item may be deemed fair and permitted by law even without permission from the rights holder(s), or the rights holder(s) may have licensed the work for use under certain conditions. For other uses you need to obtain permission from the rights holder(s).en_US
dc.subjectpulsed electric fieldsen_US
dc.subjecttissue engineeringen_US
dc.subjecthydrogelsen_US
dc.subjectbrain cancer therapyen_US
dc.subjectgliomaen_US
dc.subjectcell morphologyen_US
dc.subjectbipolar pulsesen_US
dc.subjecthigh frequencyen_US
dc.titleInvestigating the Applications of Electroporation Therapy for Targeted Treatment of Glioblastoma Multiforme Based on Malignant Properties of Cellsen_US
dc.typeDissertationen_US
dc.contributor.departmentBiomedical Engineeringen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiomedical Engineeringen_US
dc.contributor.committeechairVerbridge, Scotten_US
dc.contributor.committeememberDavalos, Rafael V.en_US
dc.contributor.committeememberRossmeisl, John H.en_US
dc.contributor.committeememberLee, Yong Wooen_US
dc.contributor.committeememberSheng, Zhien_US


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