Degree
Doctor of Philosophy (PhD)
Department
Biological and Agricultural Engineering
Document Type
Dissertation
Abstract
Cancer is a disease characterized by a wide array of dysregulated cellular function, activity, and growth. At times, specific dysregulations associated with cancer can be exploited as avenues of potential treatment. The sodium handling mechanisms and their associated proteins in cancer have received closer attention recently closely as such a potential mechanism to exploit for treating advanced cancer. Some novel treatments aim to inhibit the expression or activity of these sodium handling proteins in an attempt to prevent the cancer from advancing or becoming more aggressive; however, such approaches have had limited success. Targeted osmotic lysis (TOL) is a new and effective cancer therapy that instead leverages these dysregulated sodium handling behaviors against the cancer. In addition to its impressive efficacy, TOL also boasts an ability to treat a wide range of aggressive and advanced cancer types with an absence of any adverse effects, let alone the severe side effects that are typically associated with traditional cancer treatments. In an effort to further explore the mechanisms underlying TOL with the ultimate goal of improving and expanding its efficacy, I conducted this series of studies to evaluate at multiple levels the expression of the various subtypes of voltage-gated sodium channels (VGSCs) that are intimately associated with sodium handling mechanisms in healthy cells and several forms of cancer. I accomplished this by examining the expression patterns of these proteins at the transcriptional and translational levels in dedicated cell lines and then treating these cells with parametrically varied TOL and examining how their responses to the treatment may correlate to their VGSC regulation. These experiments showed that differences in the expression and treatment response patterns indeed are present among the cell lines evaluated and that differences in TOL parameters result in different patterns of cell death.
Date
4-4-2024
Recommended Citation
Lemoine, Spencer Gerard, "Profiling of Voltage-Gated Sodium Channel Subtype Expression and Resulting Susceptibility to Targeted Osmotic Lysis in Cancer" (2024). LSU Doctoral Dissertations. 6418.
https://repository.lsu.edu/gradschool_dissertations/6418
Committee Chair
Monroe, W. Todd