Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation

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dc.contributor.authorIvey, J. W.en
dc.contributor.authorWasson, E. M.en
dc.contributor.authorAlinezhadbalalami, N.en
dc.contributor.authorKanitkar, A.en
dc.contributor.authorDebinski, Waldemaren
dc.contributor.authorSheng, Z.en
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorVerbridge, Scott S.en
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.date.accessioned2020-07-23T15:50:17Zen
dc.date.available2020-07-23T15:50:17Zen
dc.date.issued2019-04-28en
dc.description.abstractHigh-frequency irreversible electroporation (H-FIRE) is a technique that uses pulsed electric fields that have been shown to ablate malignant cells. In order to evaluate the clinical potential of H-FIRE to treat glioblastoma (GBM), a primary brain tumor, we have studied the effects of high-frequency waveforms on therapy-resistant glioma stem-like cell (GSC) populations. We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes. This selectivity presents an opportunity for a degree of malignant cell targeting as bulk tumor cells and tumor stem cells are seen to exhibit similar lethal electric field thresholds, significantly lower than that of healthy astrocytes. However, neural stem cell (NSC) populations also exhibit a similar sensitivity to these pulses. This observation may suggest that different considerations be taken when applying these therapies in younger versus older patients, where the importance of preserving NSC populations may impose different restrictions on use.We also demonstrate variability in threshold among the three patient-derived GSC lines studied, suggesting the need for personalized cell-specific characterization in the development of potential clinical procedures. Future work may provide further useful insights regarding this patient-dependent variability observed that could inform targeted and personalized treatment.en
dc.description.sponsorshipThis work was supported by the National Cancer Institute of the National Institutes of Health through awards R21CA192042, R01CA213423, and P01CA207206 and by a National Science Foundation CAREER Award (CBET- 1652112).en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.34133/2019/8081315en
dc.identifier.urihttp://hdl.handle.net/10919/99400en
dc.identifier.volume2019en
dc.language.isoenen
dc.publisherAmerican Association for the Advancement of Scienceen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleCharacterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporationen
dc.title.serialResearchen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, School of Biomedical Engineering and Sciences
Destination Area: Adaptive Brain and Behavior (ABB)
Scholarly Works, Mechanical Engineering
Scholarly Works, Virginia Tech Carilion School of Medicine (VTCSOM)