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Application of Optical Analyses to Cancer Therapeutics and Diagnostics / ANDREW FISHER

Swansea University Author: ANDREW FISHER

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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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Published: Swansea 2020
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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first_indexed 2022-04-14T14:26:06Z
last_indexed 2022-04-15T03:31:25Z
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spelling 2022-04-14T15:43:50.8640170 v2 59833 2022-04-14 Application of Optical Analyses to Cancer Therapeutics and Diagnostics 227a5748cf564a38d21d033b10d2c17f ANDREW FISHER ANDREW FISHER true false 2022-04-14 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. E-Thesis Swansea 24 6 2020 2020-06-24 10.23889/SUthesis.59833 COLLEGE NANME COLLEGE CODE Swansea University Meissner, Kenith E. ; Shen, Haifa Doctoral Ph.D Swansea University; Houston Methodist Research Institute 2022-04-14T15:43:50.8640170 2022-04-14T15:21:18.3500479 Faculty of Science and Engineering School of Engineering and Applied Sciences - Uncategorised ANDREW FISHER 1 59833__23872__17e581442d0742939f2fd419780ab092.pdf Fisher_Andrew_P_PhD_Thesis_Final_Redacted_Signature.pdf 2022-04-14T15:34:07.9956449 Output 7613439 application/pdf E-Thesis – open access true Copyright: The author, Andrew P. Fisher, 2020. true eng
title Application of Optical Analyses to Cancer Therapeutics and Diagnostics
spellingShingle Application of Optical Analyses to Cancer Therapeutics and Diagnostics
ANDREW FISHER
title_short Application of Optical Analyses to Cancer Therapeutics and Diagnostics
title_full Application of Optical Analyses to Cancer Therapeutics and Diagnostics
title_fullStr Application of Optical Analyses to Cancer Therapeutics and Diagnostics
title_full_unstemmed Application of Optical Analyses to Cancer Therapeutics and Diagnostics
title_sort Application of Optical Analyses to Cancer Therapeutics and Diagnostics
author_id_str_mv 227a5748cf564a38d21d033b10d2c17f
author_id_fullname_str_mv 227a5748cf564a38d21d033b10d2c17f_***_ANDREW FISHER
author ANDREW FISHER
author2 ANDREW FISHER
format E-Thesis
publishDate 2020
institution Swansea University
doi_str_mv 10.23889/SUthesis.59833
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Uncategorised{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Uncategorised
document_store_str 1
active_str 0
description 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.
published_date 2020-06-24T04:17:26Z
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score 11.016235

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