Endocrine Abstracts

The expression of somatostatin (SS) receptors (sst) and dopamine (DA) D2 receptors (D2DR) on pituitary adenomas forms the basis for medical therapy using SS-analogues and DA-agonists. Different types of human pituitary adenomas variably express the five known sst subtypes, as well as D2DR. GH-secreting pituitary adenomas express predominantly sst2 and sst5 mRNA, prolactinomas mainly express sst5 mRNA, while clinically non-functioning pituitary adenomas express sst2 and sst3. I...

Background: In case of inoperable disease or tumor recurrence, there are only a few medical treatment options for patients with adrenocortical carcinoma (ACC). The oral alkylating drug Temozolomide (TMZ) shows efficacy in a subset of patients with melanoma, glioblastoma or pancreatic neurendocrine tumours. Response to TMZ seems determined by the tumoral expression level of the DNA repair enzyme O(6)-Methylguanine-DNA methyltransferase (MGMT).Aims: To eva...

Hepatocellular carcinoma (HCC) is often diagnosed at late stage or metastatic condition. Surgical resection is considered treatment of choice and other treatment options include chemoembolization, radiofrequency ablation and photodynamic therapy. We evaluated the expression levels of the 5 somatostatin receptors (SSTRs) in 23 biopsies of HCC patients and also mTOR, p70S6K and 4eBP1 in HuH-7 and HepG2 and investigated the in vitro effect of somatostatin analogs (SA) and ...

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor highly resistant to chemo-and radiotherapy. Since several reports showed that cAMP has an antiproliferative effect on different types of solid tumors both in vitro and in vivo, we evaluated the potential anti-neoplastic activity of cAMP analogues (8-Cl-cAMP and the equimolar combination of 8-PIP-cAMP and 8-HA-cAMP) in two MTC cell lines (TT and MZ-CRC-1 that harbor C634W and M918T RET mutations, respecti...

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 ...

Background: Novel treatment options are required for patients with adrenocortical carcinomas (ACCs). mTOR-inhibitors are anti-neoplastic drugs that target the mTOR-pathway.Aim: To describe the expression of the mTOR-pathway in normal and pathological adrenocortical tissues.Methods: We evaluated mRNA expression levels of mTOR, S6K and 4EBP1 in 10 normal adrenals (NA), 11 adrenal hyperplasias (AH), 19 adrenal adenomas (ACA) and 26 AC...

Introduction: Corticotroph pituitary adenomas that cause Cushing’s disease (CD) predominantly express the dopamine 2 receptor (D2) and somatostatin receptor subtype (sst) 5. The expression of sst2 is relatively low because of downregulating effects of high endogenous cortisol levels. This may explain why the sst2-preferring somatostatin analog octreotide is not effective in CD. To assess whether normalization of urinary free cortisol (UFC) excretion modulates the sst expr...

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-...

Increasing evidence has recently accumulated suggesting that IGF1 system is involved in the regulation of longevity. While in animal models alterations of IGF1 signalling increase life expectancy, in humans there are contradictory data. Centenarians are an extraordinary model to study human longevity, however, they present a number of drawbacks: rarity, frailty due to extreme age and lack of a control group of the same age. The availability of an age-matched control group is c...