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dc.contributor.advisorBrown, James
dc.contributor.advisorKerin, Michael J.
dc.contributor.authorCasey, Máire-Caitlín
dc.date.accessioned2017-09-28T11:11:26Z
dc.date.available2017-09-28T11:11:26Z
dc.date.issued2016-11-25
dc.identifier.urihttp://hdl.handle.net/10379/6840
dc.description.abstractBreast cancer is the most frequently diagnosed female malignancy worldwide, causing the majority of cancer-related deaths amongst women. While the management of this disease has transformed dramatically in recent years, personalised breast cancer management has not yet been achieved. To further inform the development of precision medicine, this thesis investigated novel mechanisms for neoadjuvant chemotherapeutic response-monitoring. With unprecedented access to scientific material, the field of microRNA (miRNA) research was analysed to enable the production of informed and targeted outputs. Recognising their known dysregulation in association with breast cancer, miRNAs were selected for analysis at the circulatory level as biomarkers of disease response to chemotherapy. Results outlined represent the initial blinded analysis of the first half of the national clinical trial that was undertaken to address this question. Upstream of miRNAs, the potential role of the miRNA-binding protein Argonaute-2 (Ago2) was analysed. Differential expression of Ago2 protein between the molecular subtypes of breast cancer was detected in-vitro, and at the tissue level in clinical breast specimens. Ago2 protein was significantly less abundant in luminal cancers, displaying inverse association with the presence of luminal receptors and direct association with metastasis, supporting a potential prognostic or predictive role. At the patient level, a novel imaging modality was introduced into the clinical setting to assess its ability to effectively visualise breast tissue. The system was optimised for clinical use, with individual breast pathologies displaying distinct photoacoustic signals. With the system optimised for clinical use and baseline parameters established, a study assessing early in-vivo tumour response detection to chemotherapy was developed and commenced. By further informing mechanisms to tailor breast cancer management on an individualised basis, work presented here contributes to the development of personalised or precision medicine, pursuing tailored chemotherapeutic administration and improved patient outcomes from this disease.en_IE
dc.subjectNeoadjuvant chemotherapyen_IE
dc.subjectMicroRNAen_IE
dc.subjectArgonaute-2en_IE
dc.subjectPhotoacoustic Imagingen_IE
dc.subjectBreast canceren_IE
dc.subjectMedicineen_IE
dc.subjectSurgeryen_IE
dc.titleNovel mechanisms for neoadjuvant chemotherapeutic response monitoring in breast canceren_IE
dc.typeThesisen_IE
dc.contributor.funderBreast Cancer Researchen_IE
dc.local.noteThe goal of this thesis was to investigate new mechanisms for detecting breast cancer response to chemotherapy. Potential indicators of disease response were assessed in patient blood samples (microRNA), in tumour tissue samples (Argonaute-2) and with an imaging system that could visualise the breast cancer within each patients' body. Each area investigated showed the potential to be used in the hospital setting to predict and monitor patient response to chemotherapy, which may enable doctors to tailor each patients treatment based on their individual responses to therapy.en_IE
dc.local.finalYesen_IE
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