Endocrine Abstracts

Background: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC). Molecular events leading to cell death in adrenocortical cells are unknown preventing the development of drugs with improved efficacy-toxicity ratio.Methods: We employed the ACC model cell line NCI-H295 to investigate the effects of mitotane on genome-wide mRNA expression using microarray analysis. Several algorithms were used to delineate signaling pathways t...

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...

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...

Adrenocortical carcinomas (ACC) are associated with heterogeneous prognosis and limited treatment options for advanced stages. Until now no efficient targeted therapies have been identified. This study aims to identify possible new molecular drug targets for a future personalized therapeutic approach. We isolated good quality RNA from 40 formalin-fixed paraffin-embedded tumor samples (33 from primary surgery, 5 from local recurrences and 2 from distant metastasis) of ACC patie...

Adrenocortical carcinomas (ACC) are associated with heterogeneous prognosis and limited treatment options for advanced stages. Until now no efficient targeted therapies have been identified. This study aims to identify possible new molecular drug targets for a future personalized therapeutic approach. RNA was isolated from 40 formalin-fixed paraffin-embedded tumor samples from ACC patients (26F&14M, median age 46 yrs) with known genetic background (Lippert et al. JCEM ...

Adrenocortical carcinoma (ACC) is an orphan tumor entity the pathogenesis of which is poorly understood. In advanced tumour stages, prognosis is unfavorable, but biomarkers for early diagnosis are lacking. MALDI-Mass Spectrometry Imaging (MALDI-MSI) enables semi-quantitative detection of a broad spectrum of analytes including endogenous cell metabolites in tissue sections. MALDI-MSI was used as a discovery approach to analyse tissue specimens of 72 ACC patients in FFPE tissue ...

Adrenocortical carcinoma (ACC) is a rare tumor with heterogeneous outcome and no available targeted therapy. The aim of the study is to identify prognostic molecular markers and novel potential drug targets.A total of 43 FFPE tumor samples were retrospectively investigated for somatic mutations and copy number variations (CNV) by next-generation sequencing (160 cancer-related genes, Qiagen). Gene expression was evaluated by quantitative RT-PCR in a subgr...

Background: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis and current medical therapies have limited efficacy in its advanced stages. Genome-wide multi-omics-studies identified molecular patterns associated with clinical outcome. Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine.Methods: 117 tumor samples from 107 AC...

Introduction: Adrenocortical tumours comprise frequent adenomas (ACA) and rare highly malignant carcinoma (ACC). Livin/ML-IAP/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumorigenesis, mostly through the inhibition of caspase-3. Aim of the study was to evaluate the expression of livin/BIRC7 in normal and neoplastic adrenal glands.Methods: The mRNA expression of BIRC7, its isoforms livin α...

Adrenocortical carcinoma (ACC) has heterogeneous prognosis and no effective targeted therapies. Pan-genomic studies identified complex molecular patterns related to outcome. Our study aimed at identification of an ‘easy-to-apply’ molecular signature for better personalized prognostic stratification. A total of 107 ACC patients were enrolled. Clinical/histopathological parameters of prognostic relevance were evaluated. Targeted molecular analysis was performed on DNA ...