Showing papers by "Richard N. Clayton published in 2015"
TL;DR: Mortality benefit from GH replacement in hypopituitarism is less pronounced in women than men and there was a potential selection bias of benefit of GH replacement from a post-marketing data necessitating further evidence from long-term randomized controlled trials.
Abstract: Context: Several previous observational studies showed an association between hypopituitarism and excess mortality. Reports on reduction of standard mortality ratio (SMR) with GH replacement have been published recently. Objective: This meta-analysis assessed studies reporting SMR to clarify mortality risk in hypopituitary adults and also the potential benefit conferred by GH replacement. Data Sources: A literature search was performed in Medline, Embase, and Cochrane library up to March 31, 2014. Eligibility Criteria: Studies with or without GH replacement reporting SMR with 95% confidence intervals (95% CI) were included. Data Extraction and Analysis: Patient characteristics, SMR data, and treatment outcomes were independently assessed by two authors, and with consensus from third author, studies were selected for analysis. Meta-analysis was performed in all studies together, and those without and with GH replacement separately, using the statistical package metafor in R. Results: Six studies reporting ...
87 citations
TL;DR: These findings show that the inverse relationship between HMGA expression and targeting miRNA is reversible through epidrug interventions, and underscore their potential as therapeutic targets in this and other diseases.
Abstract: Transgenic mice overexpressing the high mobility group A (HMGA) genes, Hmga1 or Hmga2 develop pituitary tumours and their overexpression is also a frequent finding in human pituitary adenomas. In some cases, increased expression of HMGA2 but not that of HMGA1 is consequent to genetic perturbations. However, recent studies show that down-regulation of microRNA (miRNA), that contemporaneously target the HMGA1 and HMGA2 transcripts, are associated with their overexpression. In a cohort of primary pituitary adenoma we determine the impact of epigenetic modifications on the expression of HMGA-targeting miRNA. For these miRNAs, chromatin immunoprecipitations showed that transcript down-regulation is correlated with histone tail modifications associated with condensed silenced genes. The functional impact of epigenetic modification on miRNA expression was determined in the rodent pituitary cell line, GH3. In these cells, histone tail, miRNA-associated, modifications were similar to those apparent in human adenoma and likely account for their repression. Indeed, challenge of GH3 cells with the epidrugs, zebularine and TSA, led to enrichment of the histone modification, H3K9Ac, associated with active genes, and depletion of the modification, H3K27me3, associated with silent genes and re-expression of HMGA-targeting miRNA. Moreover, epidrugs challenges were also associated with a concomitant decrease in hmga1 transcript and protein levels and concurrent increase in bmp-4 expression. These findings show that the inverse relationship between HMGA expression and targeting miRNA is reversible through epidrug interventions. In addition to showing a mechanistic link between epigenetic modifications and miRNA expression these findings underscore their potential as therapeutic targets in this and other diseases.
15 citations
03 Jul 2015
TL;DR: A literature search in Pubmed was performed as discussed by the authors, focused on articles referred to craniopharyngioma, nonfunctioning pituitary adenomas, Pituitary carcinoma, hypophysitis, germcell tumours, chordoma, cysts and empty sella syndrome.
Abstract: Space Occupying Lesions in the hypothalamic/pituitary region include tumours derived from endocrine or neural tissues, as well as a wide spectrum of more uncommon conditions such us inflammatory processes or metastases. The clinical expression of these lesions depends not only of their nature, but also on the size and position of the lesion, with some common patterns that can lead the clinician to the diagnosis, being some of them clinically silent. There is an increasing interest in the study of the molecular abnormalities in these uncommon conditions, and new drugs have started to be used as a result of the understanding of the pathways involved in the tumourigenesis. A literature search in Pubmed was performed, focused on articles referred to craniopharyngioma, non-functioning pituitary adenomas, pituitary carcinoma, hypophysitis, germ-cell tumours, chordoma, cysts and empty sella syndrome. Articles published from 2010 to 2015 in high impact factor journals were selected. Selected articles were mainly referred to new signaling pathways involved in tumourigenesis, somatic mutations, expressed receptors, new treatments and guidelines. Review articles were also used. This chapter reviews the pathogenesis, clinical manifestations and treatments of the main hypothalamic/pituitary space occupying lesions. It also provides a general and practical approach for the evaluation of these patients.
6 citations