Date of Award
Doctor of Philosophy (PhD)
Brian Booth and Delphine Dean
Triple-negative breast cancer (TNBC) continues to be one of the leading causes of death in women, making up 7% of all cancer deaths. Tumor-treating electric fields (TTFields) are low-energy, low-frequency oscillating electric fields (OEF) that have been shown to induce an anti-proliferative effect on mitotic cells in glioblastoma multiforme (GBM), non-small cell lung cancer (NSCLC), and ovarian cancer. Currently, tumor-treating field (TTField) therapy utilizes “optimal” frequencies of electric fields to achieve maximal cell death by cell line. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for maximal cell death may not exist. Finally, radio- and chemosensitization by TTFields have been observed in vitro. Current radiation treatment regimens for triple negative breast cancer (TNBC) therapy use high-energy radiation with potentially life-threatening toxicities in order to eradicate large deposits of metastatic breast cancer cells but also induce negative effects in healthy surrounding tissue. To address these issues, we developed an in-house field delivery device capable of high levels of customization to explore a much wider variety of electric field and treatment parameters. First, this study will investigate the selectivity of TTField treatment between TNBC and epithelial cells. We show a clear therapeutic window for TTField delivery to TNBC between 1 and 3 V/cm. This study will also investigate the anti-mitotic effects of modulating electric field frequency as compared to previously used uniform oscillating electric fields (OEF). We show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for preventing disease progression in cancer. Finally, with the goal of eliminating associated potentially life-threatening toxicities, we investigated the anti-mitotic effects of conjunctive TTField and fractionated ionizing radiation (IR) or chemotherapy treatment to show that disease progression was further inhibited by the addition of TTFields. We show that, when combined with TTFields, a lower effective dose of IR or chemotherapy can be used to achieve the same efficacy of TNBC cell death as higher doses of individual treatments.
SARS-CoV-2 variants of concern (VOCs) continue to pose a public health threat which necessitates a real-time monitoring strategy to complement whole genome sequencing. Thus, we investigated the efficacy of competitive probe RT-qPCR assays for six mutation sites identified in SARS-CoV-2 VOCs and, after validating the assays with synthetic RNA, performed these assays on positive saliva samples. When compared with whole genome sequence results, the S∆69-70 and ORF1a∆3675-3677 assays demonstrated 93.60 and 68.00% accuracy, respectively. The SNP assays (K417T, E484K, E484Q, L452R) demonstrated 99.20, 96.40, 99.60, and 96.80% accuracies, respectively. Lastly, we screened 345 positive saliva samples from 7 to 22 December 2021 using Omicron-specific mutation assays and were able to quickly identify rapid spread of Omicron in Upstate South Carolina. Our workflow demonstrates a novel approach for low-cost, real-time population screening of VOCs.
Smothers, Austin, "Advancement of Detection and Treatment for Triple-Negative Breast Cancer and Infectious Disease" (2023). All Dissertations. 3262.
Author ORCID Identifier