Endocrine Abstracts

Introduction: Mutations activating USP8 have been detected in a high proportion of pituitary adenomas causing Cushing’s disease and have been linked to an increase of ACTH production in corticotroph cells. Whether USP8 mutations are involved in the tumorigenesis of the ectopic Cushing’s syndrome (ECS) caused by neuroendocrine tumors has not been studied.Patients and methods: In this work we evaluate the role of USP8 in a series of 17 t...

Introduction: Regorafenib, a Tyrosine kinase inhibitor (TKI) recently approved for the treatment of metastatic colorectal cancer patients previously treated with fluoropyrimidine-based chemotherapy, VEGF and EGFR inhibitors, may, like others TKIs produce hypothyroidism, but this effect has not been systematically evaluated so far.Description of methods: Prospective evaluation of thyroid function, autoimmunity and morphology during treatment with Regorafe...

Pulmonary neuroendocrine tumors (PNTs) comprise a spectrum of neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis. To date, the role of FLNA in PNTs aggressiveness and progression is still unknown.To address this question, we decided: i) to evaluate FLNA expression in PNTs ranging from typical carc...

Neuroendocrine tumors (NETs) are uncommon neoplasms with increasing incidence and limited therapeutic options, wherein identification of new diagnostic/prognostic/therapeutic biomarkers is urgently required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of several cancers. Thus, we evaluated expression levels of SST/CORT/ghrelin system components in gastroenteropancreatic-neuroendocrine tumors (GEP-NETs...

Introduction: Neuroendocrine tumors of the lung (BP-NETs) are fairly rare tumors with very heterogeneous behavior and molecular characteristics. They are very heterogeneous concerning their malignancy, ranging from slow proliferating carcinoids (typical (TC) and atypical carcinoids (ATC)) to very aggressive large cell neuroendocrine carcinomas (LCNEC) and small cell lung cancers (SCLC). For the highly proliferative BP-NETs, combined chemotherapy is the standard therapy option,...

Background: Few effective medical treatment options are available for adrenocortical carcinoma (ACC). Intensive efforts are therefore going on for exploring novel pathways and treatment targets.Objective: To perform a proteomic and pathway analysis on a 9-cisRA (9-cis retinoic acid) and mitotane-treated ACC xenograft model.Methods: 43 male SCID mice xenografted with NCI-H295R cells were treated in four groups (i. control, ii. 5 mg/...

Embryonic transcription factors have been involved in tumourigenesis. The transcription factor TBX1 regulates the embryonic parathyroid cells fate. Indeed, it has never been investigated in human adult parathyroids. Here, expression, function and regulation of the TBX1 gene were analyzed in adult normal and tumour parathyroid tissues. Immunohistochemistry identified 30–70% (mean±S.E.M, 52.0±7.3%) of cells expressing TBX1 at nuclear levels...

Background: Heterozygous activating somatic mutations in the catalytic subunit α (Cα) of Protein Kinase A (PKA) underlie 30–40% of cortisol producing adrenocortical adenomas (CPA). The activity of the catalytic subunits α,β,γ is controlled by the regulatory subunits (Iα,Iβ, IIα, IIβ). Previous reports found uncommonly reduced levels of RIIβ in CPA compared to other adrenocortical tumors.Aim: Investig...

Gonadotropin-releasing hormone (GnRH) analogues are now the standard hormonal treatment for prostate cancer. A fundamental difference between GnRH agonist and antagonist treatment is the permanent suppression of both gonadotropins (LH and FSH) by antagonist, while a rebound in FSH is associated with agonist treatment. The benefits of antagonist include the immediate onset of action and profound long-term suppression of FSH, suggested to be an independent growth factor in prost...

An embryonic gene signature has been suggested in parathyroid tumours. We investigated the expression of early embryonic stem cell (ESC) genes in parathyroid tumours. POU5F1/OCT4, SOX2 and NANOG transcripts were detected in almost all parathyroid adenomas (PAds; n=22) and atypical PAds (n=3), besides the variable expression of ESC genes KLF4, EGR1, and REX1/ZFP42. OCT4, SOX2 and NANOG proteins expression w...