Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727646
Title: Realising the benefits of Vitamin D cancer control
Author: McClements, Jane
ISNI:       0000 0004 6425 1538
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2017
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Abstract:
Compelling observational and laboratory evidence supports vitamin D3 as a chemopreventive agent against colorectal cancer (CRC), yet its efficacy as such has not been demonstrated in clinical studies. Low-dose vitamin D3 intervention in unselected study populations, combined with a paucity of surrogate endpoint biomarkers to facilitate early phase clinical studies, may have hindered clinical translation of the cancer-suppressive effects of vitamin D3. This study aims to address these shortcomings and optimise a phase II biomarker-driven clinical study that may finally establish the efficacy of vitamin D3 in CRC chemoprevention. Using three-dimensional (3D) organotypic culture models of CRC gland architecture, vitamin D3 has been shown to exert pro-morphogenic effects and promote the maintenance of organised, epithelial gland morphology; providing a novel rationale by which this secosteroid suppresses malignant progression and invasion. This study further explores the molecular framework of vitamin D3 morphology control using the same 3D model system alongside translational studies in human CRC tissue, to identify mechanistic biomarkers of vitamin D3 cancer control that may facilitate future clinical studies. A safe, yet cancer-suppressive dose of vitamin D3 remains to be defined. It is hoped that future work evaluating the effects of an adequate, cancer-suppressive dose of vitamin D3 on novel endpoint biomarkers defined in this study may finally define the chemopreventive value of vitamin D3.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.727646  DOI: Not available
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