Searchable abstracts of presentations at key conferences in endocrinology

ea0049gp121 | Endocrine Tumours | ECE2017

Immunity in adrenocortical carcinoma patients – interplay between anti-cancer immunity and steroid hormones

Sbiera Silviu , Dexneit Thomas , Sbiera Iuliu , Schreiner Jochen , Ronchi Cristina L. , Kroiss Matthias , Fassnacht Martin

Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. By applying a ‘multiple omics’ approach, we recently identified two distinct subgroups of ACC patients, a good prognosis “immune” and bad prognosis “steroid” phenotype.We hypothesized that the steroid phenotype is associated with glucocorticoid-induced suppression that can be ‘rescued’ by reactivating the immune system using immune...

ea0037ep1125 | Endocrine tumours | ECE2015

Mitotane directly interacts with lipid membranes and alters membrane structure and dynamics

Muller Peter , Theisgen Stephan , Schirbel Andreas , Sbiera Silviu , Haralampiev Ivan , Fassnacht Martin , Huster Daniel , Kroiss Matthias

Context: Mitotane (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane) is the only drug approved for treatment of adrenocortical carcinoma (ACC). Mitotane counteracts both tumor growth and tumoural steroid hormone production but treatment is severely hampered by unfavorable pharmacokinetics and serious side effects. Mitotane is a lipophilic compound and treatment emergent alterations of lipid metabolism are frequently observed. This raises the question whether mitotane d...

ea0035p533 | Endocrine tumours and neoplasia | ECE2014

High JAG1 expression in adrenocortical carcinomas is associated with better prognosis

Ronchi Cristina , Sbiera Silviu , Steinhauer Sonja , Scott-Wild Vanessa , Fassnacht Martin , Allolio Bruno

Background: Adrenocortical tumors consist of benign adenomas (ACA) and highly malignant carcinomas (ACC). Dysregulation of the Notch signalling pathway is implicated in several cancers with oncogenic or tumor suppressor functions. JAG1 is a Notch1 ligand of the Jagged family and a common target gene for Notch and Wnt/β catenin pathways. It has been reported that upregulated expression of JAG1 enhances cell proliferation in ACC.Material and methods: ...

ea0035p535 | Endocrine tumours and neoplasia | ECE2014

Expression of inhibitor of apoptosis protein BIRC7/livin in adrenocortical tumors

Altieri Barbara , Sbiera Silviu , Steinhauer Sonja , Fassnacht Martin , Allolio Bruno , Ronchi Cristina L

Introduction: Adrenocortical tumors consist in frequent benign adenomas (ACA) and rare highly malignant carcinomas (ACC). BIRC7/livin gene, a member of the inhibitors of apoptosis family, plays an important role in tumorigenesis in a variety of malignancies. Different studies demonstrated that BIRC7 overexpression represent a risk factor for cancer development and progression. The aim of our study was to evaluate the expression of BIRC7 in normal adrenals and adrenocortical tu...

ea0070oc1.4 | Adrenal and Cardiovascular Endocrinology | ECE2020

Immune infiltrate and PD-1 / PD-L1 expression in adrenocortical carcinoma: who can predict patients´ outcome?

Landwehr Laura-Sophie , Sbiera Iuliu , Schreiner Jochen , Weigand Isabel , Kroiss Matthias , Fassnacht Martin , Sbiera Silviu

Context: Adrenocortical carcinoma (ACC) are endocrine malignant neoplasms associated with severe aggressiveness. Tumour-related glucocorticoid excess occurs in 60% of patients and is associated with poor prognosis. First clinical trials using immune checkpoint inhibitors are quite unsatisfactory and treatment advancements are urgently needed.Recently, we characterized tumour-infiltrating lymphocytes (TILs) in ACC and identified the detrimental dependency...

ea0032oc4.2 | Adrenal | ECE2013

Single nucleotide polymorphism array profiling of adrenocortical tumors: evidence for an adenoma carcinoma sequence?

Ronchi Cristina , Sbiera Silviu , Leich Ellen , Rosenwald Andreas , Allolio Bruno , Fassnacht Martin

Background: Adrenocortical tumors consist of benign adenomas (ACA) and highly malignant carcinomas (ACC) with a still incompletely understood pathogenesis. Our aim was to test, whether there is evidence for an adenoma-carcinoma sequence.Patients and methods: High-resolution single nucleotide polymorphism (SNP) microarrays (Affymetrix SNP 6.0) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH) in 46 adreno...

ea0056p132 | Endocrine tumours and neoplasia | ECE2018

Role of GLUT-2 expression and MGMT methylation for streptozotocin clinical response in adrenocortical carcinoma

Sbiera Silviu , Maukner Alfred , Kroiss Matthias , Quinkler Marcus , Beuschlein Felix , Rosenwald Andreas , Herterich Sabine , Fassnacht Martin

Introduction: Streptozotocin (SZ) is an active drug for the treatment of advanced adrenocortical carcinoma (ACC) in a minority of patients with an objective response rate of <10%. It has been reported that expression of glucose transporter-2 (GLUT-2) is essential for SZ to enter tumor cells and that high activity of O-6-methylguanine-DNA methyltransferase (MGMT) counteracts the alkylating effect of SZ. Therefore, we aimed to clarify the role of GLUT-2 and MGMT in the respo...

ea0081p385 | Endocrine-Related Cancer | ECE2022

PD-1 and PD-L1 immune checkpoint expression - the prognostic impact on adrenocortical carcinoma

Landwehr Laura-Sophie , Sbiera Iuliu , Altieri Barbara , Remde Hanna , Kircher Stefan , Sbiera Silviu , Kroiss Matthias , Fassnacht Martin

Adrenocortical carcinoma (ACC) is a very severe endocrine malignancy with poor prognosis. While cancer immunotherapies have revolutionized the treatment of several cancer entities, the results of initial studies of different immune checkpoint inhibitors in ACC were heterogeneous and clinically substantial responses were observed only in a subset of patients. Expression of immune checkpoint molecules - programmed cell death 1 (PD-1) and its ligand PD-L1 - has been shown to pred...

ea0081p153 | Pituitary and Neuroendocrinology | ECE2022

Subtype-specific pattern of white blood cell differential in endogenous Cushing’s syndrome

Detomas Mario , Altieri Barbara , Chifu Irina , Remde Hanna , Landwehr Laura-Sophie , Sbiera Silviu , Kroiss Matthias , Fassnacht Martin , Deutschbein Timo

Objective: Glucocorticoid excess impairs immune function, thereby predisposing patients with endogenous Cushing’s syndrome (CS) to infections. However, it is still not clear whether there is a CS-subtype specific pattern in white blood cell (WBC) and WBC differential (WBCD) count.Methods: Retrospective monocentric cohort study in patients with either overt endogenous CS or adrenal adenomas with autonomous cortisol secretion (ACS), with WBC and WBCD ...

ea0063gp100 | Adrenal and Neuroendocrine - Basic | ECE2019

Characterization of cell death induced by mitotane in adrenocortical carcinoma cells

Weigand Isabel , Schreiner Jochen , Rohrig Florian , Kiseljak-Vassiliades Katja , Hofner Kerstin , Kendl Sabine , Fassnacht Martin , Sbiera Silviu , Kroiss Matthias

Background: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC). We have found that mitotane leads to endoplasmic reticulum stress and decreased viability in ACC cells. It is not known by which downstream mechanisms cell death is induced by mitotane.Aim: To characterize the mechanisms underlying cell death resulting from mitotane treatment in ACC cells.Methods: Lipid peroxidation in the ACC cell line ...