Searchable abstracts of presentations at key conferences in endocrinology

ea0035p681 | Growth hormone IGF axis basic | ECE2014

Effects of two mTOR inhibitors on in-vitro models of GH-secreting pituitary adenomas

Bellio Mariaenrica , Gagliano Teresa , Zatelli Maria Chiara , Uberti Ettore Degli

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...

ea0035oc7.1 | IGF-1 and Thyroid Basic | ECE2014

GH induces chemoresistance in human endometrial cancer cell lines involving ERK 1/2 and PKCdelta

Zuolo Giulia , Minoia Mariella , Gentilin Erica , Gagliano Teresa , Tagliati Federico , Zatelli Maria Chiara , Uberti Ettore degli

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...

ea0035p538 | Endocrine tumours and neoplasia | ECE2014

Cyclin D1 levels are involved in the resistance to m-TOR inhibitors in human bronchial carcinoids

Benfini Katiuscia , Gagliano Teresa , Gentilin Erica , Minoia Mariella , Daniela Mole , Uberti Ettore degli , Zatelli Maria Chiara

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.<...

ea0035p831 | Pituitary Basic (<emphasis role="italic">Generously supported by IPSEN</emphasis>) | ECE2014

Functional characterization of a new deletion in CDKN1B 5′-UTR region

Ruvo Mauro Di , Tagliati Federico , Gentilin Erica , Gagliano Teresa , Pellegata Natalia , Benfini Katiuscia , Uberti Ettore degli , Zatelli Maria Chiara

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...

ea0041ep591 | Endocrine tumours and neoplasia | ECE2016

Mtor inhibitors responsiveness associates with Akt/Mtor pathway activation in pancreatic neuroendocrine tumors

Falletta Simona , Partelli Stefano , Rubini Corrado , Nann Dominik , Doria Andrea , Marinoni Ilaria , Polenta Vanessa , Di Paquale Carmelina , Uberti Ettore Degli , Perren Aurel , Falconi Massimo , Zatelli Maria Chiara

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...

ea0037gp.29.05 | Endocrine tumours and neoplasia – Adrenal Tumour | ECE2015

EGFR as potential new molecular target in the medical treatment of adrenocortical cancer

Gagliano Teresa , Balboni Francesco , Pasquale Carmelina Di , Gentilin Erica , Benfini Katiusci , Falletta Simona , Bondanelli Marta , Franceschetti Paola , Feo Carlo , Uberti Ettore degli , Zatelli Maria Chiara

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...

ea0037ep868 | Thyroid cancer | ECE2015

Role of miR-26a in follicular thyroid carcinoma

Gentilin Erica , Ortolan Elisa , Gagliano Teresa , Pasquale Carmelina Di , Falletta Simona , Rossi Roberta , Benfini Katiuscia , Tagliati Federico , Uberti Ettore Degli , Zatelli Maria Chiara

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...

ea0032p519 | Endocrine tumours and neoplasia | ECE2013

mTOR, AKT, p70S6K and ERK1/2 levels predict sensitivity to mTOR and PI3K/mTOR inhibitors in human bronchial carcinoids

Gagliano Teresa , Bellio Mariaenrica , Gentilin Erica , Mole Daniela , Tagliati Federico , Schiavon Marco , Cavallesco Narciso Giorgio , Calabrese Fiorella , Ambrosio Maria Rosaria , Rea Federico , Uberti Ettore degli , Zatelli Maria Chiara

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...

ea0014p205 | (1) | ECE2007

Daily and nightly urinary free cortisol ratio as a marker of the hypothalamic-pituitary-adrenal (HPA) axis activity in abdominal obesity

Vicennati Valentina , Pagotto Uberto , Ambrosi Bruno , Maccario Mauro , Uberti Ettore Degli , Boscaro Marco , Cavagnini Francesco , Mantero Franco , Armanini Decio , Vettor Roberto , Marugo Mario , Pasquali Renato

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...

ea0037ep1097 | Endocrine tumours | ECE2015

The sensitising action of a TIM16 inhibitor towards chemotherapeutic agents in human breast cancer cells depends on TIM16 expression

Gagliano Teresa , Tagliati Federico , Riva Eleonora , Zerbini Denise , Sambugaro Silvia , Gentilin Erica , Falletta Simona , Benfini Katiuscia , Pasquale Carmelina Di , Trapella Claudio , Salvadori Severo , Uberti Ettore degli , Zatelli Maria Chiara

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...