Endocrine Abstracts

Introduction: Pancreatic neuroendocrine neoplasms (PNEN) present with a fibrotic stroma which constitutes the tumor microenvironment (TME). The role played by stromal fibroblasts over the growth of PNEN and their sensitivity to the mTOR inhibitor, RAD001, are as yet unestablished.Methods: We investigated reciprocal interactions between 1) human PNEN cell lines (BON-1/QGP-1) or primary cultures of human ileal neuroendocrine neoplasm (iNEN) or PNEN, and 2)...

Introduction: Temozolomide (TMZ) treatment has been used for aggressive pituitary tumours with positive results, but has proven ineffective in controlling tumour regrowth in cases of disease recurrence. TMZ resistance has been linked to the expression of O6-methyl-guanine-DNA-methyltransferase (MGMT) protein and mismatch repair components (MMR). In the present study, we describe the development of an in vitro model of acquired resistance to TMZ and the mechanisms invo...

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...

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...

Introduction: Ketoconazole is an antifungal agent that, in a high dose, suppresses adrenocortical steroidogenesis by inhibition of cytochrome P-450 dependent enzymes. Currently, ketoconazole is used to decrease cortisol production in patients with Cushing’s syndrome. However, ketoconazole often causes gastrointestinal side effects and hepatotoxicity. Fluconazole may also inhibit steroidogenesis and has the advantage over ketoconazole that it has less side effects. Therefo...

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 ...