A Developed and Characterized Orthotopic Rat Glioblastoma Multiforme Model

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dc.contributor.authorThomas, Sean C.en
dc.contributor.committeechairVerbridge, Scotten
dc.contributor.committeememberRobertson, John L.en
dc.contributor.committeememberDavalos, Rafael V.en
dc.contributor.departmentDepartment of Biomedical Engineering and Mechanicsen
dc.date.accessioned2020-11-03T09:00:16Zen
dc.date.available2020-11-03T09:00:16Zen
dc.date.issued2020-11-02en
dc.description.abstractThis thesis project serves to fill experimental gaps needed to advance the goal of performing pre-clinical trials using an orthotopic rat glioblastoma model to evaluate the efficacy of high-frequency electroporation (H-FIRE) and QUAD-CTX tumor receptor-targeted cytotoxic conjugate therapies, individually and in combination, in selectively and thoroughly treating glioblastoma multiforme. In order to achieve this, an appropriate model must be developed and characterized. I have transduced F98 rat glioma cells to express red-shifted firefly luciferase, which will facilitate longitudinal tumor monitoring in vivo through bioluminescent imaging. I have characterized their response to H-FIRE relative to DI TNC1 rat astrocytes. I have demonstrated the presence of the molecular targets of QUAD in F98 cells. The in vitro characterization of this model has enabled preclinical studies of this promising glioblastoma therapy in an immunocompetent rat model, an important step before advancing ultimately to clinical human trials.en
dc.description.abstractgeneralTreating glioblastoma multiforme (GBM), a form of cancer found in the brain, has not been very successful; patients rarely live two years following diagnosis, and there have been no major breakthrough advances in treatment to improve this outlook for decades. We have been working on two treatments which we hope to combine. The first is high-frequency electroporation (H-FIRE), which uses electrical pulses to kill GBM cells while leaving healthy cells alive and blood vessels intact. The second is QUAD-CTX, which combines a toxin with two types of protein that attach to other proteins that are more common on the surface of GBM cells than healthy cells. We have shown these to be effective at disproportionately killing human GBM cells growing in a lab setting. Before H-FIRE and QUAD-CTX may be tested on humans, we need to show them to be effective in an animal model, specifically rats. I have chosen rat glioma cells that will behave similarly to human GBM and a rat species that will not have an immune response to them. I have made these cells bioluminescent so that we may monitor the tumors as they grow and respond to our treatments. I have also shown that QUAD-CTX kills these rat glioma cells, as does H-FIRE. Because of this work, we are ready to begin testing these two treatments in rats.en
dc.description.degreeMaster of Scienceen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:27779en
dc.identifier.urihttp://hdl.handle.net/10919/100772en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjecthigh-frequency irreversible electroporationen
dc.subjectblood-brain barrier disruptionen
dc.subjectmolecular targeted therapyen
dc.subjectbioluminescent imagingen
dc.subjectglioblastoma multiformeen
dc.subjecttumor ablationen
dc.subjectcancer therapyen
dc.subjectelectroporationen
dc.subjectdrug deliveryen
dc.subjectablationen
dc.subjectrat modelen
dc.titleA Developed and Characterized Orthotopic Rat Glioblastoma Multiforme Modelen
dc.typeThesisen
thesis.degree.disciplineBiomedical Engineeringen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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