Endocrine Abstracts

Iodide uptake via the sodium iodide symporter (NIS) is reduced in many thyroid cancers, resulting in poor prognosis following treatment with 131I. The pituitary tumor transforming gene (PTTG) and its binding factor (PBF) are proto-oncogenes implicated in thyroid tumourigenesis and we previously demonstrated PTTG and PBF-induced repression of NIS in vitro. We have recently generated murine transgenic models of targeted overexpression of PBF and PTTG in the thy...

PBF is a proto-oncogene implicated in the aetiology of thyroid cancer. PBF binds to several proteins, including PTTG and NIS, but its full function is unknown. Understanding the range of interactions PBF has within thyroid cells is therefore vital; these were explored by tandem mass spectrometry (MS/MS), which relies on the predictable fragmentation pattern of an amino acid chain to identify the exact proteins present in a sample.K1 and TPC1 papillary th...

The human pituitary tumor transforming gene (hPTTG) plays important roles in tumourigenesis through its function as a securin and by interaction with the tumour suppressor gene p53. We have previously indentified hPTTG expression as a prognostic indicator for differentiated thyroid cancer. We recently generated a transgenic mouse model overexpressing hPTTG targeted to the thyroid gland via a thyroglobulin promoter to delineate PTTG effects on thyroid tumourigenesis in vivo<...

PTTG binding factor (PBF) is a poorly characterised transforming gene that is overexpressed in thyroid tumours and inhibits the activity of the sodium iodide symporter (NIS) in vitro. Our recent investigations demonstrated that PBF mRNA expression was 2.6-fold higher in thyroid tissue excised from patients with multinodular goitres (MNG) than in normal thyroid tissue (n=25, P<0.01). We have now generated a murine transgenic model of targeted overexpres...

The human pituitary tumor transforming gene (hPTTG) is overexpressed in thyroid cancers; it induces genetic instability and propagates growth through the induction of growth factors. We set out to investigate the autocrine and paracrine pathways of interaction between hPTTG and epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and insulin-like growth factor 1 (IGF1) in vitro and in vivo. Synchronised K1 papillary thyroid carcinoma cell...

Ablative therapy for thyroid cancer depends upon the adequate uptake of radioiodine via the sodium iodide symporter (NIS). However, thyroid tumours frequently show reduced iodide uptake, impacting on prognosis. We previously demonstrated that the proto-oncogene PBF binds NIS and modulates its subcellular localisation. We now demonstrate that PBF binds the thyroid hormone transporter MCT8 in GST-pulldown assays, and alters MCT8 subcellular localisation in vitro. To inves...

The pituitary tumor transforming gene-binding factor (PBF) is a poorly characterised gene that is over expressed in pituitary and thyroid tumours. Recently we showed that subcutaneous expression of PBF elicits tumours in nude mice, and expression correlates with thyroid tumour recurrence in man. Given the established role of ionising radiation in thyroid tumourigenesis we have now investigated the relationship between PBF and the tumour suppressor protein p53. Initially, we de...

Recent studies suggest that adult humans have active brown or beige adipocytes, the activation of which might be a therapeutic strategy for the treatment of metabolic diseases. Treatment of CL-316243, a β3-adrenergic receptor agonist, activates brown/beige adipocytes and can cause significant reductions in adiposity. Many transcriptional pathways regulating brown/beige adipose tissue have been identified, the role of lipid biosynthetic enzymes in brown/beige adipose tissu...

Current systemic treatment options for patients with ACCs are far from being satisfactory. DNA damage/repair mechanisms, which involve e.g. ATM/ATR-signalling or RRM1/RRM2 encoded ribonucleotide reductase (RNR) activation commonly contribute to drug resistance. Moreover, also the regulation of RRM2b, the p53-induced alternative to RRM2, is of unclear importance for ACC. Upon extensive drug screening, including a large panel of classical chemotherapies (doxorubicin, etoposide, ...

ObjectivesThere is a paucity of real-world studies analyzing comorbidities, lab testing and treatment patterns of patients with chronic hypoparathyroidism (cHP). This study describes a large cohort of cHP patients identified using a diagnosis-based approach from a US claims database.MethodsThis retrospective study was conducted using a large (130 million individuals) claims database (HealthVerity Closed Payer...