Searchable abstracts of presentations at key conferences in endocrinology

ea0081rc6.2 | Rapid Communications 6: Endocrine-Related Cancer | ECE2022

Reciprocal interactions between fibroblast and pancreatic neuroendocrine tumor cells: putative impact of the tumor microenvironment

Cuny Thomas , Mondielli Gregoire , van Koetsveld Peter , de Herder Wouter , Barlier Anne , Hofland Leo

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)...

ea0049ep933 | Pituitary - Basic | ECE2017

Acquired temozolomide resistance in ACTH-secreting pituitary tumour cells

Silva Ticiana , Van Koetsveld Peter , Dogan Fadime , Feelders Richard , Hofland Leo

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...

ea0056p129 | Endocrine tumours and neoplasia | ECE2018

The effect of temozolomide on pancreatic neuroendocrine tumours and role of MGMT and MMR system in temozolomide resistance

Blazevic Anela , Dogan-Oruc Fadime , Dedeci Mehtap , van Koetsveld Peter M. , Feelders Richard A. , de Herder Wouter W. , Hofland Leo J.

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...

ea0041gp26 | Adrenal (2) | ECE2016

LCI699 is a potent inhibitor of cortisol production in vitro

Creemers Sara G , Feelders Richard A , de Jong Frank H , Franssen Gaston J H , de Rijke Yolanda B , van Koetsveld Peter M , Hofland Leo J

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...

ea0037ep94 | Adrenal cortex | ECE2015

Combined effects of sirolimus and mitotane in the inhibition of growth in human adrenocortical carcinoma cells

De Martino Maria Cristina , van Koetsveld Peter M , Feeldes Richard A , Lamberts Steven W J , de Herder Wouter W , Colao Annamaria , Pivonello Rosario , Hofland Leo J

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...

ea0022p22 | Adrenal | ECE2010

Comparison of the in vitro effects of ketoconazole and fluconazole on human primary adrenocortical cultures and on the adrenocortical carcinoma cell line HAC15

van der Pas Rob , Hofland Leo , Waaijers Marlijn , de Jong Frank , Uitterlinden Piet , de Herder Wouter , van Koetsveld Peter , Feelders Richard

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...

ea0020p52 | Adrenal | ECE2009

Expression of mTOR pathway in human adrenocortical carcinomas and in vitro effects of mTOR inhibitors in human adrenocortical cell lines

De Martino Maria Cristina , van Koetsveld Peter , Sprij-Mooij Diana , Feelders Richard A , Lamberts Steven W J , de Herder Wouter W , Colao Annamaria , Pivonello Rosario , Hofland Leo J

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 ...