Endocrine Abstracts

Introduction: In case of inoperable disease or tumor recurrence, therapy with mitotane (MIT), sometimes in combination with doxorubicin (DOX), etoposide (ETO), cisplatin (CIS) or streptozocin (STREP), is frequently applied in patients with adrenocortical carcinoma (ACC). The multidrug resistance pump MDR1 is responsible for resistance of tumor cells to cytostatic drugs. The activity of MDR1 is inhibited by the calcium-channel blocker verapamil. There are equivocal data in the ...

Introduction: ACTH stimulates adrenocortical steroid production through the melanocortin 2 receptor (MC2R). MC2R trafficking and signaling depend on the melanocortin 2 receptor accessory protein (MRAP). The MRAP-homolog MRAP2 also transports the MC2R but prevents effective activation. We investigated expression of these components of the MC2R complex in human adrenal tissues in order to uncover novel regulatory mechanisms and their contribution to ACTH responsiveness.<p cl...

Introduction: Neuroendocrine tumors (NET) are rare tumors originating from various types of neuroendocrine cells. The somatostatin receptor type 2 (sst2) is expressed in NET cells and is a target for therapy with somatostatin analogues.Epigenetic changes including methylation of DNA at CpG dinucleotides, and particularly in the promoter region of genes can inhibit transcription. Methylation can be inhibited by cytidine analogues such as 5-aza-...

Background: Of the currently available treatment regimes for acromegaly, pegvisomant (PEG-V) has the highest efficacy. During PEG-V treatment, GH serum levels increase. The exact mechanism behind this is remains unclear. It could be explained by an ultra-short feedback loop via GH receptors in the anterior pituitary gland.Objective: To assess the level of GH receptor (GHR) mRNA expression in somatotroph adenomas and to evaluate whether GHR blockade by PE...

The pathogenesis of pheochromocytomas (pheo) is poorly understood and malignant pheo need new treatment options. mTOR inhibitors, as sirolimus (S) and everolimus (E), are new promising antineoplastic drugs.Aim: To evaluate whether the IGF/mTOR pathways have a role in the pathogenesis and whether S and E may have antiproliferative effects in pheo.In 24 human pheo and two normal adrenal medulla (NM), we evaluated the mRNA expression ...

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Many patients with ACC need new treatment options. mTOR inhibitors, as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several kinds of tumors.Methods: In three human ACC cell lines (H295, HAC15 and SW13), we evaluated the mTOR and IGF2 expression at mRNA level (by qPCR) and at protein ...