Endocrine Abstracts

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 ...

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...

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...

Pancreatic neuroendocrine tumours (NETs) are reported to show frequent mutations in chromatin remodelling genes, while pituitary NETS have alterations in histone modification. Histone modifications, and specifically acetylated residues on histone tails are recognised by members of the bromo and extra terminal (BET) protein family, via their bromodomains, causing alterations in the transcription of growth stimulating genes. BET bromodomain inhibitors have been demonstrated to s...

Neuroendocrine tumours (NETs), occurring at multiple sites including the pancreas, gastrointestinal tract, lung, thymus and pituitary, usually present at an advanced metastatic stage, and are increasing in incidence and prevalence as awareness and diagnostic techniques have improved. Treatments for NETs including surgery, drugs (e.g. somatostatin analogues), chemotherapy, radiotherapy and radionuclide therapy, are often not effective and as such additional therapeutic agents a...