Gao, Han
2024.
Electromagnetic radiation and its impact on cancer treatment.
PhD Thesis,
Cardiff University.
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Abstract
Microwave technology has emerged as a significant tool in medical applications, particularly in cancer treatment. Traditional microwave ablation generates high temperatures, leading to patient discomfort and potential unwanted tissue damage. Our research aims to apply microwave signals under normothermic conditions to minimize such effects. This thesis investigates the efficacy and underlying mechanisms of pulsed electromagnetic field exposure (PEFE) in treating breast and colorectal cancers, which are the most common and the fourth most common cancers in the UK, respectively. A PCI eXtensions for Instrumentation (PXI)-based system was developed to improve efficiency, accuracy, and repeatability in PEFE applications. The new system integrates essential components, maintains a stable temperature, and automates processes, enhancing experimental consistency. The main purpose of this study is to reveal the potential mechanism of PEFE, applied at microwave range, in inducing cell deaths in vitro in both colorectal cancer (CRC) and breast cancer (BRCA). Further investigations revealed that PEFE treatment induces apoptosis in cancer cells, with tight junctions playing a crucial role in facilitating signal transduction. Therefore, we identified MarvelD3, a novel tight junction-associated protein, and explored its clinical and functional significance in colorectal cancer and breast cancer. MarvelD3 was found to be differentially expressed in breast and colorectal cancers. Its expression levels correlated with patient outcomes, suggesting its potential as a prognostic marker. By manipulating the expression of MarvelD3 in CRC and BRCA cell lines, we demonstrated that MarvelD3 regulates cellular adhesion, invasion, and migration negatively in both cancers. Interestingly, while MarvelD3 inhibits CRC cell growth, it promotes BRCA cell growth. MarvelD3 emerged as a biomarker for PEFE treatment; the knockdown of MarvelD3 led to decreased efficiency of PEFE in both CRC and BRCA cells. Proteomic analysis identified several dysregulated molecules post-PEFE treatment, particularly those involved in apoptosis, tight junction formation, and cell membrane integrity, confirmed by a series of Western blots. In summary, this thesis demonstrates the potential of PEFE as an effective cancer treatment, XV elucidates the role of tight junctions and MarvelD3 in mediating its effects, and highlights critical signalling pathways involved in cancer cell response to PEFE. These findings contribute to the development of more precise and less invasive cancer treatments.
Item Type: | Thesis (PhD) |
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Date Type: | Completion |
Status: | Unpublished |
Schools: | Schools > Engineering |
Uncontrolled Keywords: | 1) Microwave application 2) Cancer treatment 3) Breast cancer 4) Colorectal cancer 5) Tight junction 6) Cell deaths |
Date of First Compliant Deposit: | 14 March 2025 |
Last Modified: | 14 Mar 2025 16:28 |
URI: | https://orca.cardiff.ac.uk/id/eprint/176895 |
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