Biospectroscopy towards screening and diagnosis of cancer

Theophilou, Georgios (2015) Biospectroscopy towards screening and diagnosis of cancer. PhD thesis, UNSPECIFIED.

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Systems biology is an emerging science that combines high throughput investigation techniques to define the dynamic interplay between different biological regulatory systems in response to internal and external cues. Related technologies, genomics, epigenomics, transcriptomics, proteomics, metabolomics and toponomics have been applied to investigate models of carcinogenesis to identify committing initiating events. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches, as it is able to identify chemical bond alterations within molecules independent of where these molecules reside. Its integration with current “systems biology” methodologies can contribute in the identification of potential biomarkers of carcinogenesis and assist in their incorporation into clinical practice. Breast tissue undergoes cyclical and longitudinal molecular and histological alterations that are influenced by environmental factors. These factors may include diet and lifestyle in addition to parity, lactation and menopausal status and are implicated in carcinogenesis. Breast cancer may appear decades after the initial carcinogenic event. Available research in this area is limited to when early histological changes occur due to the difficulties imposed by the molecular and histological diversity of breast tissue. Vibrational spectroscopy in combination with powerful chemometric techniques has identified spatial and temporal mammary alterations in benign tissue. Prostate cancer is influenced by environmental factors. Its incidence is higher in populations adopting a Westernised lifestyle and diet and has increased over the past generation. This leads to the assumption that prostatic tissue composition may exhibit chronological alterations. Vibrational spectroscopy techniques were applied to matching prostatic tissues with benign prostatic hyperplasia collected from 1983 to 2013. Significant trans-generational segregation was identified. Spectral areas responsible for this segregation pointed towards epigenetic changes. Immunohistochemical studies for DNA methylation and hypomethylation supported these results. Vibrational spectroscopy techniques were also implemented to explore molecular changes between normal ovarian tissue, borderline ovarian tumours and malignant ovarian carcinomas. Different chemometric techniques were applied to discriminate cancers from controls. Similar techniques were able to segregate different types of epithelial ovarian carcinomas. The accurate diagnosis obtained using ATR-FTIR spectroscopy demonstrates its potential for development as an assisting tool for histopathological diagnosis. The endometrial-myometrial junction areas of benign uterine tissues were scrutinised by Synchrotron FTIR and FPA. These techniques in combination with multivariate analysis revealed clear segregation between the functionalis and basalis layers within the uterine crypts. The same techniques illustrated potential areas within these epithelial surfaces where different stem cell types may reside. Targeting the activation/ inactivation of these stem cells may have applications in the diagnosis and treatment of early uterine cancer.

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Thesis (PhD)
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30 Nov 2015 09:40
Last Modified:
12 Sep 2023 00:17