Endocrine Abstracts

Background: Gigantism and acromegaly are the main consequences of GH excess, mainly due to a pituitary adenoma. Surgery is the first therapeutic option, but also medical therapy is employed, being represented mostly by somatostatin analogues (SSA), that reduce both tumour mass and GH hypersecretion. However about 10% of patients is resistant to SSA.PI3K/Akt/mTOR pathway, activated by growth-factors such as IGF1, is important in regulating many cellular p...

Background: Surgery is the main therapeutic option for advanced endometrial cancer; however, when disease relapses, chemotherapy is the only option. Chemoresistance is a very common phenomenon in these tumors. We previously demonstrated that GH protects breast cancer cells towards the cytotoxic effects of doxorubicin, inducing chemoresistance. Recent evidences show that endometrial cancer cells secrete GH, stimulating their own growth in an autocrine fashion.<p class="abst...

Background: Bronchial carcinoids (BC) are still orphan of medical therapy. We previously demonstrated that the typical BC human cell line NCI-H727 is sensitive to Everolimus, in terms of cell viability reduction, while the atypical human BC cell line NCI-H720 is not. However, the mechanisms underlying this phenomenon have not been fully clarified.Aim: The aim of our study is to investigate the mechanisms of resistance to mTOR inhibitors in BC cells.<...

Introduction: CDKN1B gene, which encodes a cyclin-dependent kinase (Cdk) inhibitor, regulates the progression throughout G1 to S cell cycle progression. CDKN1B loss-of-function germinal mutations cause the multiple endocrine neoplasia type 4 syndrome (MEN4).Objective: The aim of the study is the functional characterization of a new 4 bp deletion in CDKN1B 5′-UTR region, identified in an acromegalic patient.Materials and metho...

Introduction: Medical therapy of Pancreatic neuroendocrine tumors (P-NETs) may take advantage from mammalian target of rapamycin (mTOR) inhibitors. However, so far, the extent of therapeutic response cannot be predicted.Aim: To investigate the possible predictors of sensitivity to mTOR inhibitors in P-NETs.Materials and methods: P-NET primary cultures were treated with IGF1 and/or Everolimus. Cell viability and caspase activity wer...

Adrenocortical cancer (ACC) is a rare and aggressive malignancy. Currently the main therapeutic option is surgery, but due to difficult and delayed diagnosis and to the onset of metastases, medical therapy is often tried. ACC treatment is mainly represented by Mitotane alone or in association with chemotherapy, with variable results. Understanding the molecular mechanisms that regulate ACC proliferation could be useful to identify new therapeutic options. Sunitinib, a multitar...

Follicular thyroid carcinoma (FTC) is the second most common thyroid malignant epithelial tumor. It is clinically asymptomatic, usually represented by a single nodule, less often multiple, with origin from thyroid follicular epithelial cells. Despite its well-differentiated characteristics, FTC may develop distant metastases through hematogenous dissemination. The molecular alterations involved in the pathogenesis of follicular neoplasia are not completely known. Recent studie...

Background: Bronchial carcinoids (BCs) are rare neuroendocrine tumors that are still orphan of medical treatment. Human BC primary cultures may display resistance to everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), in terms of cell viability reduction.Aim: To assess whether the novel dual PI3K/mTOR inhibitor, NVP-BEZ235, may be effective in everolimus-resistant human BC tissues and cell lines. In addition, we search for possible mark...

Abdominal obese (AO) women might have a hyperactivation of the HPA axis. The limitations of previous studies have been often represented by the limited and heterogeneous number of patients enrolled. Our aim was to asses urinary free cortisol (UFC) output during daily and nightly hours in a large cohort of AO women vs. normal weight controls (CT). 107 AO women and 37 CT were enrolled in the study. In basal condition, each subject underwent OGTT, biochemical determinations. Each...

TIM16 a component of the translocase complex TIM23 of the mitochondrial inner membrane is encoded by the Magmas gene. Magmas was found to be over-expressed in human pituitary adenomas. Silencing Magmas in ACTH secreting rat pituitary adenoma cells enhances sensitivity to pro-apoptotic stimuli. Moreover, Magmas overexpression protects GH secreting rat pituitary adenoma cell lines towards apoptosis. Recently, we found that compound 5, a TIM16 inhibitor, is not cytotoxic but enha...