E-Thesis 191 views 93 downloads
Application of Optical Analyses to Cancer Therapeutics and Diagnostics / ANDREW FISHER
Swansea University Author: ANDREW FISHER
DOI (Published version): 10.23889/SUthesis.59833
Abstract
The extreme diversity and heterogeneity of cancer cells creates a need for equally varying analysis methods to diagnose and treat the disease. Many methods have been developed for targeting and combatting a specific cancer. The oestrogen receptor, HER2, is overexpressed in certain varieties of breas...
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Swansea
2020
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | Ph.D |
| Supervisor: | Meissner, Kenith E. ; Shen, Haifa |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa59833 |
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| Abstract: |
The extreme diversity and heterogeneity of cancer cells creates a need for equally varying analysis methods to diagnose and treat the disease. Many methods have been developed for targeting and combatting a specific cancer. The oestrogen receptor, HER2, is overexpressed in certain varieties of breast cancer and subsequently used as a target for chemotherapy antibody treatments. 1 Unfortunately, not all cancers overexpress an easily identifiable protein and are therefore limited to systemic, non-targeted therapies such as resection, radiation, and chemotherapy. 2 Here, three novel techniques are investigated for analysing cancer therapeutic and diagnostic techniques. Porous silicon microparticle (PSM) delivery methods take advantage of tumour vessel tortuosity and fenestrations to selectively deliver cancer therapeutics to tumours. In chapter 2, the previously uncharacterized rolling mechanics of PSM on endothelial cells are examined at physiologically relevant shear rates. Custom analysis software allows for the identification, tracking, and characterization of particles in flow. Tertiary lymphoid structures (TLS) in and around tumours have been prominently associated with positive patient prognoses but are difficult and time consuming to identify. In chapter 3, optical tissue clearing and 3D imaging are utilized to investigate the ability of dendritic cell (DC) vaccines and checkpoint blockade therapies to affect tumour growth in association with TLS presence in the tumour. When treated with the DC vaccine or a combination with anti-PD1 treatments, tumour growth is severely inhibited. The 3D imaging and analysis was used to correlate the tumour growth inhibition with an increase in the concentration of intratumoural T cells and of TLS present in the tumour. Optical spectroscopic imaging of biological systems has important applications in medical diagnosis and biochemistry. However, the extrinsic fluorescence of staining molecules often masks the intrinsic vibrational signals of biomolecules. In chapter 4, simultaneous spectroscopic bioimaging and photostability analysis of rhodamine 6G stained red blood cells using both fluorescence and resonance Raman imaging in a single laser excitation experiment were performed. A corresponding data processing algorithm was developed to separate the two previously indistinguishable spectroscopic signals. |
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| College: |
Faculty of Science and Engineering |