Endocrine Abstracts

Cancer cells have shown an overexpressed fructose transporter GLUT5 and preferential utilization of fructose as compared to glucose, implicating that a fructose-based analogue would be a useful target for diagnosis and treatment of cancer. We have successfully synthesized the fructose conjugated-gefitinib compounds {N-[4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxy-quinazolin-6-yl]-4- [N-methyl-N-(1-deoxy-1-fructosyl)]aminobutanamide}, and examined its antitumor effic...

Introduction and Aims: Graves’ disease (GD) is mediated by thyroid stimulating antibodies (TSAbs) to the TSH receptor (TSHR). Treatments for GD have remained unchanged for more than 40 years with less than 50% of patients achieving long term remission with medical therapy. Experimental animal models have been described which facilitate understanding of disease mechanisms and permit studies of novel immunotherapeutic interventions. However studies aiming to perturb the Th1...

CRF mediates numerous complementary stress-related endocrine (HPA), autonomic and behavioral responses. CRF antagonists block many stress-induced responses in experimental animals. Furthermore, perturbations of the CRF system or HPA have been reported in human affective disorders. CRF acts through two Class B G protein coupled receptors derived from two genes, which have alternative splice variants and distinct expression patterns. Mice null for CRF-R1 exhibit reduced basal an...

Background:Circulating levels of IGFBP-3 are inversely associated with the risk of developing colorectal cancers (CRC). In addition to modulating IGF bioavailability, IGFBP-3 also exerts independent pro-apoptotic effects. Furthermore, the mode of action of several apoptotic and antiproliferative agents, including vitamin D, has been shown to involve induction of IGFBP-3.Aims:To quantitate and compare IGFBP-3 ...

Introduction: Subcutaneous (sc) pasireotide effectively reduces cortisol levels, improves signs/symptoms and is generally well tolerated in Cushing’s disease (CD) patients, as shown in previous clinical trials. We report interim results from a multicentre, real-world observational study evaluating the long-term safety and efficacy of pasireotide sc in clinical practice in CD patients.Methods: Adults with CD, for whom surgery has failed or is not an ...

Bile acids (BAs) are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). Modulation of bile acid profiles might affect the treatment of metabolic diseases, indicating new possible therapeutic avenues. The sodium taurocholate co-transporting polypeptide (NTCP) plays a pivotal role in the enterohepatic circulation of bile salts as the main uptake transpo...

Background: Gastrointestinal neuroendocrine tumors (GI NETs) are subdivided into grades (G) G1-G3 based on Ki-67 proliferation index (%) (G1<3%, G2 3-20%, and G3 >20%) or mitotic rate, with tumor grade informing prognosis and treatment. Grade progression (GP) over time in GI and pancreatic NETs has recently been identified, with low(G1/2)-to-high(G3) grade progression (L-to-H) the most clinically relevant form. L-to-H is associated with worse survival, yet the timefram...

Background: Pancreatic neuroendocrine tumors (panNETs) are heterogeneous, with grade (G) defined by Ki67 proliferation index (<3% G1, 3-20% G2, and >20% G3) or mitotic rate. Previous studies suggest that baseline Ki67 index may be confounded by biopsy site (primary or metastasis), biopsy technique and primary tumor size. Ki67 differences leading to grade discordance in PanNETs at baseline is relatively understudied. Our study aims to evaluate grade discordance in synch...

Kisspeptin is integral to hypothalamo-pituitary-gonadal (HPG) axis function and overall fertility. Functional deficiency of GnRH/lH secretion in the central reproductive disease, hypothalamic amenorrhoea (HA), indicates diminished kisspeptin signalling. Clinical trials have shown kisspeptin to be a viable therapeutic intervention. However, repeated administration led to the development of tachyphylaxis and so is likely a problem for future implementation. Indeed, elevated LH r...

Primary adrenal insufficiency in children can be due to mutations in >20 genes, most commonly CYP21A2, giving rise to 21-hydroxylase deficiency. Phenotypically these disorders overlap and present with conditions ranging from isolated (or familial) glucocorticoid deficiency (FGD) to syndromic disorders involving multiple tissues. Distinguishing between them can be problematic, especially where biochemical testing is not possible or not undertaken. Over the last 30 ...