Ettore degli Uberti

University of Ferrara | UNIFE

Background: Hypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacologi...

Background: Hypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacologic...

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, de...

Background: BRAFV600E (c.1799T>A) somatic mutation evaluation in fine needle aspiration biopsies (FNAB) is a powerful diagnostic tool in the settings of papillary thyroid cancer (PTC). However, its prognostic value is still a matter of great debate and has been addressed mostly in retrospective studies. Objectives: To evaluate whether the somati...

PurposeInsulin-like growth factor 1 (IGF1) controls growth hormone (GH) secretion via a negative feed-back loop that may disclose novel mechanisms possibly useful to control GH hyper-secretion. Our aim was to understand whether PI3K/Akt/mTOR pathway is involved in IGF1 negative feedback on GH secretion. Methods Cell viability, GH secretion, Akt, an...

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Indeterminate thyroid nodules include heterogeneous lesions that could benefit from a differential management. Our aim is to better define the management of the Bethesda System for Reporting Thyroid Cytopathology class III and IV nodules, by identifying cytological subcategories among Bethesda System for Reporting Thyroid Cytopathology class III as...

Growth Hormone may influence neoplastic development of endometrial epithelium towards endometrial adenocarcinoma, which is one of the most occurring tumors in acromegalic patients. Since chemoresistance often develops in advanced endometrial adenocarcinoma, we investigated whether Growth Hormone might influence the development of chemoresistance to...

Background In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term efficacy and safety. AimWe here reviewed the emerging aspects of the use of PEG in clinical practice in the light of the mos...

Background Human herpesviruses have been hypothesized as environmental triggers in the development of autoimmune thyroid diseases (AITD), and in particular active human herpesvirus 6A (HHV-6A) infection was detected in thyrocytes of Hashimoto’s thyroiditis (HT) patients, who also show specific anti-viral immune responses. On the other hand, AITD pa...

MicroRNAs (miRNAs) are non-coding RNAs generated from endogenous hairpin-shaped transcripts that powerfully regulate gene expression at post-transcriptional level. Each miRNA is capable to regulate the expression levels of hundreds of transcripts and each mRNA may have more than one miRNA recognition sequence. There is emerging evidence that deregu...

Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viability and induced apoptosis in pri...

Background: Information regarding the safety of herbal drugs is often not reported. We describe the case of a 65-year-old woman referred to us for a iatrogenic hypercortisolism, who denied any previous steroid consumption. She reported only a chronic application of a phytocosmetic cream, containing ethanol extract of the Cardiospermum halicacabum...

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 cul...

Introduction: It is known that growth hormone (GH) may influence neoplastic development of endometrial epithelium. GH is produced by normal and neoplastic endometrial cells and elevated levels have been observed in endometrial epithelium of patients with endometriosis and endometrial adenocarcinoma (EA). Moreover, endometrium cancer is one of the m...

The incidence of thyroid nodules is increasing, representing a malignant neoplasm only in 5–15 % of cases. Preoperative, ultrasonographically guided fine-needle aspiration biopsy (FNAB) is the cornerstone of thyroid-nodule evaluation. Most diagnostic FNAB are read as cytopathologically benign or malignant, but 15–30 % remain indeterminate [1]. The...

Hashimoto’s thyroiditis (HT) is a very common autoimmune disease of the thyroid. In addition to genetic background, several viruses, including herpesviruses, have been suggested to play a role as possible environmental triggers of disease, but conclusive data are still lacking. Previous results showed that HT patients have an increased cellular imm...

Protein Kinase C Delta (PRKCD) has been highlighted among disrupted pathways in corticotroph adenomas. PRKCD is expressed at low level in human corticotroph adenomas and controls cell cycle in vitro. Therefore, PRKCD may play an important role in the development/progression of corticotroph adenomas, warranting further studies to understand the role...

Medical treatment of adrenocortical carcinoma (ACC) is still far from optimal, since even molecular targeted therapy failed to demonstrate striking results. Clinical trials enrolling ACC patients with high tissue Vascular Endothelial Growth Factor Receptor (VEGFR) expression levels showed controversial results after treatment with Sunitinib, possib...

Context Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. It has been previously demonstrated that insulin-like growth factor I (IGF-I) protects MTC from the effects of antiproliferative drugs. Everolimus, an mTOR inhibitor, has shown potent antiproliferative effects in a human MTC cell line, TT, and...

Surgery is not feasible for infiltrating and metastatic bronchopulmonary NET(BP-NET). In those cases, medical therapy is tried with controversial results. Thus, it is important to identify new therapeutic targets to provide adequate medical treatment for patients with BP-NET. Sunitinib, is a multi-targeted receptor tyrosine kinase inhibitor (TKI),...

Introduction: Neuroendocrine tumours (NETs) are heterogeneous neoplasms arising from neuroendocrine cells spread in the respiratory and gastro-entero-pancreatic epithelium. The role of transforming growth factor beta-1 (TGFβ1) in NET biology is largely unknown. TGFβ1 signalling pathway is tumour suppressive in most non-transformed epithelial cell l...

Background: Bronchial carcinoids (BC) are rare neoplasm, still orphan of medical therapy, which arise from neuroendocrine cells. It has been previously demonstrated that the atypical BC human cell line NCI-H720 is sensitive to everolimus (E), an m-TOR inhibitor, in terms of cell viability reduction, with a G0 cell-cycle arrest and a Cyclin D1 prote...

We found that Magmas protein (Tim16) in the MCF7 cell line is highly expressed as compared to MDA-MB231 cells and MCF12A. Our data show that treatment with compound 5 did not influences cell viability in the 3 cell lines , while Doxorubicin decrease this parameter by 20-30%. Only in MCF7 co-treatment with compound 5 enhance the antiproliferative ef...

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 mostly represented by somatostatin analogues (SSA), that reduce both tumour mass and GH hypersecretion. However about 10% of patients is resistant to SSA...

TIM16, a protein of the translocase complex TIM23 of the mitochondrial inner membrane, is encoded by the Magmas a gene. Magmas silencing has been associated with a greater sensitivity to apoptotic stimuli in pituitary adenoma cell lines. We recently demonstrated that in a human medullary thyroid carcinoma cell line (TT) compound 5, a TIM16 inhibito...

Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapi...

The truncated somatostatin receptor variant sst5TMD4 associates with increased invasiveness and aggressiveness in breast cancer. We previously found that sst5 activation may counteract sst2 selective agonist effects in a medullary thyroid carcinoma (MTC) cell line, the TT cells, and that sst5TMD4 is overexpressed in poorly differentiated thyroid ca...

Genetic alterations frequently are involved in the development of a pituitary adenoma in young age. We here characterize the functional role of a deletion in CDKN1B 5'-UTR region (c.-29_-26delAGAG) identified in an acromegalic patient that developed a growth hormone in pituitary adenoma during childhood. Our results show that the identified novel h...

Purpose Rare endocrine–metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism,...

Background: A molecular profile including BRAF and RAS mutations as well as RET/PTC rearrangement evaluation has been proposed to provide an accurate presurgical assessment of thyroid nodules and to reduce the number of unnecessary diagnostic surgeries, sparing patients' health and saving healthcare resources. However, the application of such mole...

Mitotane is currently employed as adjuvant therapy as well as in the medical treatment of adrenocor-tical carcinoma (ACC), alone or in combination with chemotherapeutic agents. It was previously demonstrated that mitotane potentiates chemotherapeutic drugs cytotox-icity in cancer cells displaying chemoresistance due to P-glycoprotein (P-gp), an eff...

Introduction Pituitary function is influenced by several drugs, including anti-depressant, opioids, glucocorticoids, chemotherapeutic agents, immunomodulators and the newly developed tyrosine kinase inhibitors. In most instances, treatment with these drugs negatively affects pituitary function, but in rare cases an activation of specific hypothala...

Background: Prospective uncontrolled study to investigate in papillary thyroid carcinoma (PTC) patients: (1) Distribution of lymph node metastases within the neck compartments, (2) factors predicting lymph nodes metastases, and (3) disease recurrence after thyroidectomy associated with radio-guided selective compartment neck dissection (RSCND). M...

We recently demonstrated that Magmas overexpression protects GH-secreting rat pitutitary adenoma cell lines from apoptosis by inhibiting cytochrome c release from mitochondria after treatment whit Staurosporine, strongly suggesting a role of Magmas in preventing apoptosis. The aim of this study was to produce a drug that, by inhibiting Tim16, may s...

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...

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 i...

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. Rece...

Adrenocortical cancer (ACC) is still orphan of medical treatment. Our preliminary data show that EGF induces ACC cell lines proliferation (+20 and +10% vs control in SW13 and NCI-H295 cell lines respectively). EGF receptor (EGFR) expression is higher and ubiquitous in SW13 cells, while it is weaker in NCI-H295 cells, where it is present only on the...

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....

Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors and pituitary adenomas, due to inactivating mutations of the MEN1 gene (chromosome 11q13). MEN1 mutations are mainly represented by nonsense, deletions/insertions, splice site or missen...

Mitotane represents the mainstay medical treatment for metastatic, inoperable or recurrent adrenocortical carcinoma. Besides the well known adverse events, mitotane therapy is associated also with endocrinological effects, including sexual and reproductive dysfunction. The majority of male patients undergoing adjuvant mitotane therapy show a pictur...

Bisphosphonates (BPs) are the first-line therapy for osteoporosis. In recent years, atypical femoral fractures (AFF) have been described in patients on BPs therapy. However, the relationship between BPs and AFF remains to be clarified. We evaluated clinical and hormonal characteristics of AFF patients, in order to determine AFF risk factors. We stu...

Medical therapy for Cushing's disease (CD) is currently based on agents mainly targeting adrenocortical function. Lately, pituitary-directed drugs have been developed, with limited efficacy. Mitotane, a potent adrenolitic drug, has been recently investigated for the treatment of CD, but the direct pituitary effects have not been clarified, so far.T...

The optimal method of assessing GH status in acromegalic patients receiving medical therapy with somatostatin analogs (SSA) has been matter of debate. The aim of the study has been to investigate whether OGTT may add information in patients with discordant random GH (GHr) and IGF values. Moreover, we evaluated the association of GH nadir with the p...

Bronchial carcinoids (BC) 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. Our aim is to assess whether the novel dual PI3K/mTOR inhibitor, NVP-BEZ235, may be effec...

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 b...

Protein kinase C (PKC) is a family of serine-threonine kinases that regulate many cellular processes including proliferation and survival. Previous evidence has shown that PKC is involved in the control of human medullary thyroid carcinoma (MTC) proliferation and survival by modulating apoptosis, with a mechanism that implicates PKCβII isoform and...

The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting...

Background Concomitant papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) is a frequent occurrence. Whether these two conditions are linked and whether PTC with concurrent HT has distinct clinicopathological characteristics are still debated issues. Lymphocytic infiltration is abundant in HT and might be relevant in the pathogenesis an...

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...

Bronchial carcinoids (BC) are rare tumors originating from endocrine cells dispersed in the respiratory epithelium. Currently, the main BC treatment is surgery, that can be curative in most of the cases, but is not feasible for large, infiltrating and metastatic disease. In these settings, medical therapy is often tried, being mainly represented by...

Hashimoto's thyroiditis (HT) is the most common of all thyroid diseases and is characterized by abundant lymphocyte infiltrate and thyroid impairment, caused by various cell- and antibody-mediated immune processes. Viral infections have been suggested as possible environmental triggers, but conclusive data are not available. We analyzed the presenc...

Germline mutations of aryl-hydrocarbon-receptor interacting protein (AIP) are associated with pituitary adenoma predisposition. They occur in 20 % of familial isolated pituitary adenoma (FIPA) and in about 3-5 % of sporadic pituitary adenomas, especially in early onset somatotropinomas and prolactinomas. Our aim was to evaluate the clinical and gen...

Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the most reliable nonsurgical test for distinguishing benign from malignant thyroid nodules. However, there is no consensus on which nodules should undergo FNAB. The aims of this study were to evaluate the utility of US-guided FNAB in the diagnostic assessment of nodules with or without...

GH and IGF-I play a role in breast cancer (BC) development. We previously demonstrated that GH protects the estrogen receptor (ER) positive BC-derived MCF7 cell line toward the cytotoxic effects of doxorubicin (D), independently of IGF-I. This issue may be important in ER negative BC cells that are more aggressive and more likely to develop chemore...

We investigate the role of protein kinase C (PKC) in the control of medullary thyroid carcinoma (MTC) cell proliferation by a PKC inhibitor, Enzastaurin, in human MTC primary cultures and in the TT cell line. We found that PKC inhibition reduces cell proliferation by inducing caspase-mediated apoptosis and blocks the stimulatory effect of IGF-I on...

Dopamine (DA) therapy of non-functioning pituitary adenomas (NFA) can result in tumor stabilization and shrinkage. However, the mechanism of action is still unknown. Previous evidence showed that DA can inhibit pituitary vascular endothelial growth factor expression (VEGF), that may be involved in pituitary tumor growth. The aim of our study was to...