Endocrine Abstracts

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that negatively regulate gene expression through imperfect base pairing to the 3′ untranslated regions (UTRs) of target mRNAs. We have investigated the role of the miR-15a–miR-16-1 cluster in pituitary tumourigenesis, as it functions in other cancers as a tumour suppressor via regulation of the cell-cycle regulator cyclin D1. We have used two approaches: 1) in vitro studies examinin...

Familial Juvenile Hyperuricaemic Nephropathy (FJHN) is an autosomal dominant disorder that is associated with gout and progressive renal failure. FJHN in 43 families has been reported to be caused by mutations in the UMOD gene, which encodes Uromodulin, also known as the Tamm-Horsfall Glycoprotein, and two families have been reported to have mutations in the transcription factor Hepatocyte Nuclear Factor 1β (HNF-1β), mutations of which usually cause maturity-o...

Pancreatic endocrine tumours (PETs) have a low proliferation index and this partially accounts for their lack of response to chemotherapy. The assessment of proliferation rates relies largely on the use of markers such as Ki67 in patients, and uptake of DNA nucleotide precursors such as tritiated thymidine or 5-bromo-2-deoxyuridine (BrdU) in animals. Amongst these, BrdU is recognised to be the most reliable marker of cell proliferation as it allows the substitution of an endog...

D cells comprise 3–10% of the human endocrine pancreas and secrete somatostatin, which inhibits cell proliferation and hormone secretion. Pancreatic tumours secreting somatostatin are associated with the somatostatinoma syndrome, which is characterised by hyperglycaemia, cholethiasis, a low acid output and anaemia. We have examined for the presence of somatostatin secreting cells in pancreatic tumours from a multiple endocrine neoplastic type 1 (MEN1) knockout mouse model...

The Na+/I- symporter (NIS) is a plasma membrane glycoprotein that mediates active I- transport in the thyroid follicular cells (the first step in thyroid hormone biosynthesis), and in other tissues, such as lactating mammary gland. NIS is the basis for the effective use of radioiodide in the diagnostic and treatment of thyroid cancer. NIS mutations hae been identified as causes of congenital iodide transport defect (ITD). We have isolated the cDNA that encodes NIS, generated h...

Dent's disease is an X-linked renal tubular disorder characterised by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis. The disease is caused by inactivating mutations of a renal-specific chloride channel, hCLC-5, that belongs to the family of mammalian voltage-gated chloride channels (CLCs). Heterologous expression of wild-type CLC-5 in Xenopus oocytes results in chloride (Cl-) conductance, which is markedly reduced or abolished by the m...

2-Methoxyoestradiol (2-MeOE2) is a human endogenous metabolite of oestradiol which is known to inhibit the proliferation of breast cancer cells. Sulphamoylation of 2-MeOE2 greatly enhances its ability to inhibit breast cancer cell proliferation and induce apoptosis. To establish whether 2-MeOE2 and its mono- and bis-sulphamoylated derivatives would also be an effective treatment for other endocrine cancers, we have investigated their effects, and those of 2-ethyloestradiol (2-...

Ovarian cancer is the leading cause of death from all gynaecological malignancies. The observation that decreased levels of the natural oestrogen-17beta metabolite, 2-methoxyoestradiol (2-MeOE2) may create a predisposition to oestrogen dependent cancer, has led to considerable interest in the potential use of oestrogen derivatives for the prevention and treatment of hormone dependent cancers. The sulphamoylated oestrone derivative 2-methoxyoestrone-3-O-sulphamate (2-MeO...

Background: Education in diabetes is a fundamental component of self-management. Health care systems that have structured education from diagnosis have demonstrated improving trends in HbA1c. Within Wales, education for Children and Young People (CYP) was delivered informally and this deficiency was highlighted in the National Paediatric Diabetes Audit. While structured education is being delivered in some parts of the UK, there is no overarching programme covering the entire ...

Approximately 230 new patients with GEP-NEN are referred annually to the centre. Prevalence of GEP-NEN is increasing due to the availability of 2nd, 3rd or 4th line treatments. Oral chemotherapy is being used with increasing frequency in this setting. The NEN Team wished to explore the outcomes of patients treated with temozolomide singe agent and temozolomide/capecitabine during the previous 5 years and compare the findings with current literature. 18 patients were included i...