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High Frequency Irreversible Electroporation (H-FIRE) as a Therapeutic Modality for Liver Cancer Treatment and Its Effect on the systemic Extracellular Vesicle Population

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dc.contributor.authorTellez Silva, Alejandraen
dc.contributor.committeechairDervisis, Nikolaosen
dc.contributor.committeememberKlahn, Shawna L.en
dc.contributor.committeememberDavalos, Rafael V.en
dc.contributor.departmentBiomedical and Veterinary Sciencesen
dc.date.accessioned2024-08-03T08:00:10Zen
dc.date.available2024-08-03T08:00:10Zen
dc.date.issued2024-08-02en
dc.description.abstractHigh-frequency irreversible electroporation (H-FIRE) is a non-thermal ablation technique that uses intense, short, bipolar electrical pulses to induce cell death in cancerous tissues. It's being studied for treating hepatocellular carcinoma (HCC) in dogs. Previous in vitro research suggests H-FIRE may impact the release of extracellular vesicles (EVs). This study aims to explore how H-FIRE affects peripheral extracellular vesicle (EV) dynamics, potentially providing insights into its broader systemic effects and implications for biomarker development in canine liver cancer treatment. Dogs diagnosed with HCC were enrolled in a clinical trial. H-FIRE was applied to tumors, followed by surgical resection at three different time points. Peripheral blood samples were collected before and immediately after H-FIRE treatment. Plasma was isolated, aliquoted, and stored at -20°C. EVs were enriched from plasma via filtration and ultracentrifugation. Nanoparticle Tracking Analysis (NTA) quantified EV concentration and size distribution. Ten patients provided pre- and post-treatment plasma samples. The median EV concentration in peripheral blood increased from 2.56 x 10^11 particles/ml pre-treatment to 2.68 x 10^11 particles/ml post-treatment (p = 0.0048). The mean EV size decreased from 99.32 nm pre-treatment to 87.82 nm post-treatment (p = 0.007). The mode of EV size decreased from 83 nm pre-treatment to 70.5 nm post-treatment (p = 0.0076). The results of this study raise intriguing questions on the significance of changes in extracellular vesicle size and concentration post-treatment, as well as the potential clinical implications of these changes.en
dc.description.abstractgeneralHigh-frequency irreversible electroporation (H-FIRE) is a new method to destroy cancer cells without using heat. It's being tested for treating liver cancer in dogs. Previous lab studies suggest H-FIRE might affect the release of small structures known as extracellular vesicles (EVs). This study aims to see how H-FIRE affects EVs in the blood of dogs with liver cancer. Understanding these changes could help develop new ways to diagnose and treat the disease in dogs and humans. Dogs with liver cancer were part of a study. They received H-FIRE treatment followed by surgery, and blood samples were taken before and right after treatment. The plasma was separated and stored. EVs were collected from plasma using special methods, including Nanoparticle Tracking Analysis (NTA) to help measure the number and size of EVs.en
dc.description.degreeMaster of Scienceen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:41233en
dc.identifier.urihttps://hdl.handle.net/10919/120843en
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectHepatocellular carcinomaen
dc.subjecthigh frequency irreversible electroporationen
dc.subjectextracellular vesiclesen
dc.subjectcanine.en
dc.titleHigh Frequency Irreversible Electroporation (H-FIRE) as a Therapeutic Modality for Liver Cancer Treatment and Its Effect on the systemic Extracellular Vesicle Populationen
dc.typeThesisen
thesis.degree.disciplineBiomedical and Veterinary Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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