Searchable abstracts of presentations at key conferences in endocrinology

ea0031oc5.7 | Pituitary and neoplasia | SFEBES2013

Uterine tumours with loss of progesterone receptor expression develop in mice deleted for a cell division cycle 73 allele

Walls Gerard , Manek Sanjiv , Thakker Rajesh

Mutations of the cell division cycle 73 (CDC73) gene, which encodes the 531 amino acid protein parafibromin, are associated with the Hyperparathyroidism-Jaw Tumour (HPT-JT) syndrome, an autosomal dominant disorder characterised by parathyroid tumours and ossifying jaw fibromas. In addition, ∼75% of women with HPT-JT develop benign and malignant uterine tumours, which include endometrial hyperplasia, adenosarcomas, adenofibromas, and leiomyomas. To explore the role of <em...

ea0031p152 | Neoplasia, cancer and late effects | SFEBES2013

Parathyroid gland studies in mouse models for endocrine tumours defines anatomical locations and ultrastructural differences between normal and tumour cells

Walls Gerard , Clark Anne , Thakker Rajesh

Investigation of parathyroids in mouse models is hampered by difficulties in identifying the small glands. We developed a microsurgical technique to identify murine parathyroids by dissecting from the distal thyrothymic ligament to the lower thyroid pole (LTP). Parathyroids were identified in 100 mice which comprised: 48 mice deleted for a cell-division-cycle 73 gene allele (Cdc73+/−), involved in the hyperparathyroidism-jaw tumour syndrome; ...

ea0046p6 | (1) | UKINETS2016

Whole-exome next generation sequencing of sporadic adrenocortical carcinomas - evidence for a proposed adenoma-carcinoma carcinogenesis sequence

Walls Gerard , Salatino Silvia , Wright Benjamin , Mihai Radu

Limited survival of patients with adrenocortical carcinoma (ACC) makes it imperative to understand the genetic basis of disease and support development of new therapies.Between 2010–2015, tissues from nine adrenalectomy patients (5M:4F, age 30–68 years) were snap frozen in liquid nitrogen and DNA extracted. Adjacent normal adrenal tissue (n=3) excised at adrenalectomy was collected as matched ‘normal’ controls. Whole-exome se...

ea0021p225.1 | Endocrine tumours and neoplasia | SFEBES2009

The microRNA let-7a is downregulated in pituitary tumours from a multiple endocrine neoplasia type-1 mouse model

Dyar Rebecca , Newey Paul , Nesbit Andrew , Walls Gerard , Thakker Rajesh

MicroRNAs are highly conserved non-coding RNAs that regulate diverse cellular processes. Altered microRNA expression is observed in many human cancers and microRNAs may have tumour suppressor or oncogenic properties. One group of putative tumour suppressor microRNAs is the let-7 family whose expression is reduced in several human tumours, and which inhibit the expression of several oncogenes including HMGA2 and K-Ras. Let-7 expression have also been observed to b...

ea0038p146 | Neoplasia, cancer and late effects | SFEBES2015

The somatostatin analogue pasireotide decreased proliferation and increased apoptosis in pancreatic and pituitary neuroendocrine tumors in a MEN1 mouse model

Stevenson Mark , Walls Gerard , Soukup Ben , Lines Kate , Grossman Ashley , Schmid Herbert , Thakker Rajesh

Improved therapies for pancreatic and pituitary neuroendocrine tumors (NETs), which may occur in Multiple Endocrine Neoplasia type 1 (MEN1), are needed. We assessed the effects of pasireotide, a somatostatin analogue with high affinity for somatostatin receptors (SSTRs) −1, −2, −3 and −5, in a mouse model of MEN1. Men1+/− mice treated from 12 months of age with 40 μg/g pasireotide (n=71), or phosphate-buffered sal...

ea0038p302 | Pituitary | SFEBES2015

Menin regulates the expression of miR-15a, which is downregulated and inversely correlates with cyclin D1 expression in mouse Men1-associated pituitary tumours

Lines Kate E , Newey Paul J , Yates Chris J , Walls Gerard V , Thakker Rajesh V

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid, pituitary and pancreatic islet tumours, and is due to mutations of the MEN1 gene, which encodes the tumour suppressor protein menin. MicroRNAs (miRNA) are non-coding single stranded RNAs that post-transcriptionally regulate gene expression. Alterations in miRNA expression, including downregulation of two miRNAs, miR-15a and miR-16-1, have been r...

ea0031yep1.1 | Young endocrinologists' prize lectures | SFEBES2013

Clinical and pre-clinical studies of neuroendocrine tumours (NETs) in multiple endocrine neoplasia type 1 (MEN1), and evaluation of MEN1 gene replacement therapy for MEN1-associated NETs.

Walls Gerard , Newey Paul , Lemos Manuel , Javid Mahsa , Piret Sian , Reed Anita , Thakker Rajesh

We have studied clinical and pre-clinical models to investigate neuroendocrine tumour (NET) development and efficacy of novel therapy for NETs. We focused on multiple endocrine neoplasia type 1 (MEN1), an autosomal dominantly inherited condition characterised by the combined occurrence of pancreatic islet and anterior pituitary NETs with parathyroid and adrenocortical tumours. MEN1 is due to MEN1 gene mutations that inactivate Menin, a tumour suppressor. Our clinical studies r...

ea0021oc2.2 | Neuroendocrine tumours/pituitary | SFEBES2009

Wnt/β-catenin signalling is down-regulated in pituitary tumours from a multiple endocrine neoplasia type 1 (MEN1) mouse model

Walls Gerard , Newey Paul , Nesbit M Andrew , Jeyabalan Jeshmi , Schulz Herbert , Huebner Norbert , Thakker Rajesh

The tumour suppressor menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, has been reported to be a component of the Wnt/β-catenin signalling pathway. To investigate the effects of menin loss on this pathway, we have determined the cDNA expression profiles of pituitary tumours from 5 Men1+/− mice and in normal pituitaries from 5 Men1+/+ littermates by extracting total RNA and by hybridizing it to Affymetrix Mous...

ea0021oc3.4 | Young Endocrinologists prize session | SFEBES2009

MicroRNAs, let-7 and miR-302, have an altered expression in Men1-null embryos, consistent with abnormal embryonic development

Bowl Michael , Newey Paul , Reed Anita , Walls Gerard , Baban Dilair , Nesbit Andrew , Thakker Rajesh

The multiple endocrine neoplasia type 1 (MEN1) gene, which when mutated gives rise to parathyroid, pancreatic and pituitary tumours, has been shown to have a role in embryogenesis, as Men1-null mice (Men1−/−) are embryonic lethal by 12.5 days post coitum (dpc). MicroRNAs (miRNAs) are emerging as potent regulators of early mammalian embryogenesis, and we therefore undertook expression profiling of miRNAs in Men1+/+ and M...

ea0021p304 | Pituitary | SFEBES2009

Pituitary tumours of mice deleted for a multiple endocrine neoplasia type 1 allele have alterations in apoptotic pathway components

Walls Gerard , Newey Paul , Jeyabalan Jeshmi , Nesbit A Michael , Schulz Herbert , Huebner Norbert , Thakker Rajesh

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of anterior pituitary, pancreatic islet and parathyroid tumours. Mice (Men1+/−) deleted for an MEN1 allele develop these tumours. The MEN1 gene encodes a 610 amino acid protein that has been reported to upregulate caspase 8 expression and promote apoptosis. To characterize the functional effects of menin loss in vivo, we asse...