Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016

Abstract: U.K. guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults 2016 D. Creamer, S.A. Walsh, P. Dziewulski, L.S. Exton, H.Y. Lee, J.K.G. Dart, J. Setterfield, C.B. Bunker, M.R. Ardern-Jones, K.M.T. Watson, G.A.E. Wong, M. Philippidou, A. Vercueil, R.V. Martin, G. Williams, M. Shah, D. Brown, P. Williams, M.F. Mohd Mustapa and C.H. Smith Department of Dermatology, King’s College Hospital NHS Foundation Trust, London SE5 9RS, U.K. St Andrews Centre for Plastic Surgery and Burns, Mid Essex Hospital Services NHS Trust, Chelmsford CM1 7ET, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. Dermatology Unit, Singapore General Hospital, Singapore Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, U.K. Mucosa and Salivary Biology, Dental Institute, King’s College London, Guy’s Campus, Great Maze Pond, London SE1 9RT, U.K. University College Hospital, London NW1 2BU, U.K. Clinical Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, U.K. Department of Dermatology, Orpington Hospital, Orpington, Kent BR6 9JU, U.K. Department of Dermatology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, U.K. Department of Histopathology and Intensive Care Medicine, King’s College Hospital NHS Foundation Trust, London SE5 9RS, U.K. Late of the Burns Centre, Chelsea and Westminster NHS Foundation Trust, London SW10 9NH, U.K. Department of Burns and Plastic Surgery, University Hospitals of South Manchester, Southmoor Road, Wythenshawe, Manchester M23 9LT, U.K. St John’s Institute of Dermatology, Guy’s and St Thomas NHS Foundation Trust, London SE1 9RT, U.K.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Elastography in Non-Hepatic Applications: Update 2018

Abstract: This manuscript describes the use of ultrasound elastography, with the exception of liver applications, and represents an update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography.

Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.

Abstract: Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.