Endocrine Abstracts

Studies on the distribution of Somatostatin Receptor (sst)-subtypes on endocrine tumors, the development of sst-subtype specific analogues, the elucidation of phenomena like receptor desensitization and ligand-receptor internalization, and the potential consequences (and reversal) of the epigenetic silencing of sst offer new diagnostic and therapeutic modalities in endocrine diseases:1. apart from sst2 activation, Somatostatin analogues target...

Background: Pancreatic Neuroendocrine Neoplasms (pNENs) are malignancies arising from the endocrine pancreas. Past in vitro studies have led to a better comprehension and characterization of this malignancy under several points of view. However, effective medical therapies are still not available, therefore, it is essential to continue studying this malignancy in order to identify a successful approach. Due to tumour complexity, techniques such as 3D cultures, able to...

: Pancreatic neuroendocrine tumours (pNETs) are rare neoplasms arising from the endocrine pancreas. The fist line treatment is surgery that is often not curative in the presence of metastatic disease. Therefore, there is an increasing need for medical therapy. Sunitinib is a multi-target receptor tyrosine-kinase (RTK) inhibitor, described as having as main target VEGF receptor, with antitumor and antiangiogenic effects, approved for pNETs medical treatment. This study is aimed...

Finding new preclinical models to study the effects of anticancer drugs is one of the aims of biomedical research. Indeed, testing different in vitro systems can lead to a better understanding of the molecular pathways regulating tumor development and growth, and help to find new therapeutic approaches. This is crucial especially in the settings of pancreatic neuroendocrine tumours (pNET), where one of the main drugs approved for medical treatment is Sunitinib, a mult...

Background: Temozolomide (TMZ) has been suggested as a treatment option for patients with pancreatic neuroendocrine tumours (PNETs). The tumour response to TMZ has been linked to expression levels of O6-methylguanine-DNA methyltransferase (MGMT) and components of the mismatch repair (MMR) system. However, there is no in vitro data on TMZ sensitivity and the expression of MGMT and MMR components in PNETs. Moreover, the effect of TMZ exposure on chemosensitivity and exp...

Background: Previous studies indicate that PAS-LAR can achieve control of insulin-like growth factor I (IGF-I) levels and may reduce tumor size, however a subset of acromegaly patients responds poorly. T2-signal intensity, somatostatin receptor (SST) subtype 2 and 5 expression, and the response to first-generation somatostatin receptor ligands (SRLs) are recognized predictors of therapy response. Valid prediction of the response to PAS-LAR can alter treatment stratification.</...

Introduction: The steroidogenesis inhibitors ketoconazole and metyrapone are frequently used for treatment of Cushing’s syndrome, but can cause side effects. LCI699 is a known 11β-hydroxylase inhibitor, but effects on other steroidogenic enzymes are unknown. We aimed to compare effects of LCI699, ketoconazole, and metyrapone in vitro.Methods: HAC-15 cells, with or without 10 nM ACTH, and three primary human adrenocortical adenoma cultu...

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. Mitotane alone, or in combination with cytotoxic chemotherapy, represents the referral current treatment for patients with unresectable ACC. Recent studies have shown that mTOR inhibitors suppress growth of ACC cells. This study aimed at evaluating the effects of mitotane in combination with mTOR inhibitors. In H295 and SW13 cells we tested the effects of a 6 day treatment with increa...

The mTOR and IGF/insulin pathways are frequently dysregulated in HCC. Antitumoral activity of mTOR inhibitors (mTORi) has been demonstrated in experimental models but in early clinical studies mTORi alone have shown modest antitumoral activity. IGF/insulin-dependent Akt activation, via IGF1R and IR, has been suggested as potential mechanism for mTORi resistance. This study aimed at evaluating the expression of mTOR and IGF/insulin pathway components and the effects of mTORi al...

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Surgery, performed at early stages, offers the best chance for cure, but unfortunately, it is often noncurative. Medical treatment produced disappointing responses. mTOR inhibitors, such as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several types of carcinomas.Methods: To evaluate ...