Endocrine Abstracts

Adrenocortical carcinoma (ACC) is a rare and aggressive tumour with a poor prognosis, characterized by radio/chemotherapy resistance. The lack of an effective medical treatment is due to the poor knowledge of the mechanisms underlying malignant tumour transformation and aggressiveness. In vitro studies on the ACC H295R cell model have demonstrated that RGZ, an antidiabetic drug belonging to the thiazolidinedione ligands of PPARgamma, blocks cell proliferation/migration ...

Germline mutations in the RET gene cause MEN2, an inherited cancer syndrome associated with medullary thyroid carcinoma (MTC). We performed genetic analysis on DNA from whole blood of a 58 yr old female affected by a multifocal MTC. Exons 10, 11, 13, 15 and 16 of RET gene were amplified by PCR using specific primers and characterised by direct automatic sequencing. Here, we report a new RET point mutation: a heterozigous missense mutation Y606C, a G to A nucleotide substitutio...

Fascin-1(FSCN1) is an actin-bundling protein expressed in several solid carcinomas and often associated to an invasive and aggressive phenotype as it is involved in cytoskeleton rearrangement and filopodia formation. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by a poor prognosis, particularly when metastatic at diagnosis. Complete surgical resection of the tumor mass is the main therapy for ACC patients in addition to the adjuvant administratio...

Background: Extracellular vesicles (exosomes, microvesicles) shed from tumor cells containing microRNAs can be exploited as markers of malignancy. The preoperative diagnosis of adrenocortical malignancy is difficult and microRNAs have proved useful in the diagnosis of many tumors, including adrenocortical cancer (ACC), but there have no studies to date on extracellular vesicle associated microRNAs in ACC.Aim: To evaluate the diagnostic potential of extra...

Adrenocortical cancer (ACC) is a rare aggressive malignancy, with poor prognosis when metastaic at diagnosis. Recent ACC pan-genomics analysis contributed to redefine the risk groups on molecular bases, including tumor micro RNA (miR), which can be detectable not only in the primary lesion but also in the bloodstream.We develop a quantitative real-time assay for the measurement of absolute levels in plasma samples of miR483 and its mature miR483-5p form....

The potential therapeutic applications of targeting brown adipose tissue open new clinical avenues in fighting against metabolic pathologies. However, due to the limited brown depots in adult humans, dramatically reduced after birth, solid cell models to study human brown adipogenesis and its pathophysiological regulation are urgently needed.In our study, we characterized a novel human model of brown adipose stem cells, hfB-ASC, derived from fetal inters...

Background: The differential expression of tissue microRNAs in benign and malignant adrenocortical tumours has been described in several studies including ours. Novel data show that microRNAs are also present in the bloodstream and can be exploited as minimally invasive markers of malignancy.Objective: To analyze the microRNAs expressed in different studies by an in silico approach and to establish the molecular pathways affected. Furthermore, circulatin...

The recent discovery of the presence of brown adipose tissue (BAT) also in human adults is pivotal for development of anti-obesity therapies. This type of fat, in fact, mainly consists of brite cells (brown adipocytes appearing for a browning process in white fat) which are involved in adiposity control. The origin of brite cells in adult white adipose tissue (WAT) is still unclear as human cell models are lacking.Our study demonstrated the presence of B...

Besides their well-known anti-diabetic effects, the peroxisome proliferator-activated receptor γ (PPARγ) thiazolidinedione ligands (TZD) have been suggested to also display anti-inflammatory properties. The receptor role in mediating such effects is far from being elucidated. Here, we demonstrate that PPARγ is necessary for TZD to interfere with TNFα and IFNγ inflammatory activity in human endothelial cells. Different PPARγ ligands similarly inhib...

The molecular mechanisms underlying the reawakening of hypothalamic GnRH neurons at puberty remain to be elucidated. Recently, the G protein-coupled receptor 54 (GPR54) and its endogenous ligand kisspeptin, encoded by the KISS1 gene, have been involved. In fact, GPR54 mutations cause idiopathic hypogonadotropic hypogonadism in human and mice. We used the previously characterized primary culture of human fetal olfactory GnRH-secreting neurons, FNC-B4, to study in vitro t...