ORCID Profile
0000-0002-2680-6200
Current Organisation
Trinity College Dublin
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Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.CTRV.2017.03.005
Abstract: Metformin, a primary treatment for diabetes mellitus (DM) patients, is associated with improved outcomes for diabetic cancer patients fuelling further investigation on its mechanisms of action. The radiosensitising properties of metformin are increasingly reported in pre-clinical studies. This review discusses whether metformin should be offered to radiotherapy (RT) cancer patients as a means to improve their treatment outcomes. A database search was conducted for articles published with metformin as the main intervention between 2010 and 2016. Three groups of RT cancer patients were analysed: diabetic patients using metformin, diabetic patients not using metformin and non-diabetic patients not using metformin. Data on survival and recurrence metrics were extracted. Thirteen studies were included. Conflicting evidence exists with regards to the impact of metformin administration on recurrence and survival outcomes following radiotherapy. Three studies reported improved tumour response determined by recurrence rates while five studies did not observe differences or metformin use was not the associated reason. One study revealed inconsistent tumour response results. Metformin was reported as improving survival outcomes in 2 studies and not improving outcomes in 5 studies. 4 studies showed indefinite results. Although metformin may improve tumour response in the non-randomized, retrospective studies analysed, it may not necessarily confer survival benefits. Future prospective and randomised trials are required to translate the positive impact of metformin documented in pre-clinical and retrospective studies into improve management of RT cancer patients.
Publisher: Springer Science and Business Media LLC
Date: 22-11-2019
DOI: 10.1038/S41598-019-53799-7
Abstract: The exact biological mechanism governing the radioresistant phenotype of prostate tumours at a high risk of recurrence despite the delivery of advanced radiotherapy protocols remains unclear. This study analysed the protein expression profiles of a previously generated isogenic 22Rv1 prostate cancer model of radioresistance using DigiWest multiplex protein profiling for a selection of 90 signalling proteins. Comparative analysis of the profiles identified a substantial change in the expression of 43 proteins. Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were independently validated using Western Blotting. Pharmacological targeting of these proteins was associated with a mild but significant radiosensitisation effect at 4Gy. This study supports the clinical relevance of isogenic in vitro models of radioresistance and clarifies the molecular radiation response of prostate cancer cells.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.CTRV.2017.08.011
Abstract: The Notch pathway is a highly conserved pathway increasingly implicated with the progression of human cancers. Of the four existing receptors associated with the pathway, the deregulation in the expression of the Notch-3 receptor is associated with more aggressive disease and poor prognosis. Selective targeting of this receptor has the potential to enhance current anti-cancer treatments. Molecular profiling strategies are increasingly incorporated into clinical decision making. This review aims to evaluate the clinical potential of Notch-3 within this new era of personalised medicine.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.RADONC.2018.05.029
Abstract: Standard of care radiotherapy in LA-NSCLC is 60-66 Gy in 30-33 fractions. However outcomes for these patients are poor with 5-year survival in the range of 10-20%. Randomised controlled trials have shown that dose escalation in a linear fashion does not improve outcomes for all patients, thus there is a need to tailor the prescription to the in idual patient. This review assesses the strategies published to personalise the radiation therapy dose prescription in LA-NSCLC. A systematic and scoping search of the literature was performed to identify studies that met the inclusion criteria. 19 relevant studies were identified ranging from prospective clinical trials to mathematically modelled concept studies. Heterogeneity existed between all clinical studies. Nine heterogeneous publications proposed methodology to adapt the dose prescription to the in idual patient. A number of encouraging strategies have been identified but fall short of the evidence level required to influence clinical practice.
Location: France
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Laure Marignol.