Endocrine Abstracts

Pancreatic neuroendocrine tumours (PNETs) are increasing in incidence, and have a 5-year survival rate of <50%. This is largely because, despite recent advances, current treatments are often ineffective, and therefore additional therapeutic agents are required. Epigenetic inhibitors may offer a novel class of anti-cancer drugs, as PNETs harbour mutations of chromatin remodelling genes including ATRX and DAXX, while menin, encoded by MEN1, interac...

Current treatments, including surgery, medical therapy, radiotherapy, and radionuclide therapy for neuroendocrine tumours of the pancreas (PNETs) and bronchus (BNETs) are often unsatisfactory, leading to a 5-year survival of <50% and 5%, respectively. PNETs and BNETs frequently have mutations in chromatin-remodelling genes and the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin. Menin binds the...

Current treatments, including surgery, medical therapy, radiotherapy, and radionuclide therapy for neuroendocrine tumours of the pancreas (PNETs) and bronchus (BNETs) are often unsatisfactory, leading to a 5-year survival of <50% and 5%, respectively. PNETs and BNETs frequently have mutations in chromatin-remodelling genes and the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin. Menin binds the...

Corticotrophinomas represent >10% of all surgically removed pituitary adenomas, which are the most commonly encountered intracranial neoplasms that are identified in >25% of unselected autopsies and approximately 20% of the population undergoing intracranial imaging. Corticotrophinomas are associated with hypersecretion of adrenocorticotropic hormone (ACTH), which leads to excessive production of glucocorticoids by the adrenal cortex and the resulting hypercortisolemia causes ...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by occurrence of parathyroid tumours and neuroendocrine tumours (NETs) of the pancreas and pituitary, which is caused by mutations of the MEN1 gene, encoding menin. Mouse models are important in elucidating mechanisms of MEN1 tumourigenesis and treatments, but the current models have limitations. Thus, in conventional heterozygous MEN1 knockout models, tumour d...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid tumours, and neuroendocrine tumours (NETs) of the pancreas and pituitary. Reliable biomarkers, ideally in plasma or serum, for the early detection and recurrence of MEN-1 associated tumours, and especially pancreatic NETs are required, and we explored the potential use of microRNAS (miRNAs), which are small non-coding RNAs that bind target mRNAs ...

Epigenetic modifications and chromatin remodelling have been demonstrated to play a key role in the development, and progression of multiple cancers, and compounds regulating these mechanisms represent a novel class of anti-cancer drugs. Menin, which is encoded by the MEN1 gene, whose mutations result in a syndrome characterised by pituitary, parathyroid and pancreatic islet tumours, binds histone modifying enzymes, including the histone methyltransferase MLL1. Furthe...

JQ1 is a bromodomain inhibitor that specifically targets the BET protein family (comprising Brd2, Brd3, Brd4 and BrdT), which promote the transcription of genes by binding acetylated histone residues and recruiting transcriptional machinery. JQ1 has been shown to have efficacy in the treatment of neuroendocrine tumours, however the genes regulated by the BET family in endocrine tissues, particularly in the pituitary, have not been elucidated. We therefore performed RNA-Seq ana...

Neuroendocrine tumours (NETs), occurring at multiple sites including the pancreas, lung and pituitary, are increasing in incidence and usually present at an advanced metastatic stage, and current medical treatments have limited efficacy. Epigenetic modifiers are promising new drugs, as mutations in the multiple endocrine neoplasia type 1 (MEN1) gene, encoding the histone methyltransferase MLL1 interacting protein, menin, are known to cause both familial and sporadic N...

There are currently no curative treatments for metastatic pancreatic neuroendocrine tumours (PNETs), and the 5-year survival is <50%. Such tumours frequently have mutations in chromatin remodelling genes as well as the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin, which is mutated in up to 40% of sporadic PNETs, and binds the histone methyltransferase MLL1. Histone modifications, and specifically acetylated residues on histone tail...