Endocrine Abstracts

Context: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC) and in clinical use for more than 50 years. Mitotane counteracts both tumour growth and tumoral steroid hormone production but treatment is associated with severe side effects. The molecular mechanism of mitotane is still unknown, which hampers progress in treatment of ACC.Objective: To identify the mechanism of action and molecular target of mitotane.<p class...

Recently, we demonstrated for adrenocortical carcinoma (ACC) promising antitumoural effects for LEDP-M (etoposide, liposomal doxorubicin, liposomal cisplatin, mitotane) a novel liposomal variant of the classical EDP-M protocol (etoposide, doxorubicin, cisplatin, mitotane). However, clinical translation of novel therapeutic regimens remains challenging due to high tumor heterogeneity. Thus, to obtain preclinical results with more clinically predictive power we investigated for ...

Primary aldosteronism caused by aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia is the most prevalent cause of secondary hypertension. Somatic mutations of KCNJ5, ATP1A1, CACNA1D and ATP2B3 have been shown to be involved in the formation of APA. We studied the immunoexpressions of CYP11B2 and HSD3B2, the rate-limiting enzyme for aldosterone production and the prevalent isoform of β-HSD found in APA respectively, and...

Background: Current drug treatment options for adrenocortical carcinoma (ACC) are rather limited and intensive efforts are going on to find novel effective agents. In our previous functional genomics study, retinoid signalling via the retinoid X receptor (RXR) was identified as a major pathogenic pathway in ACC and we have demonstrated the in vitro activity of 9-cis retinoic acid (9-cisRA) acting via the RXR on NCI-H295R cells and also found that 9-cisRA has antitumou...

Adrenocortical cancer (ACC) is a rare and aggressive malignancy. Currently the main therapeutic option is surgery, but due to difficult and delayed diagnosis and to the onset of metastases, medical therapy is often tried. ACC treatment is mainly represented by Mitotane alone or in association with chemotherapy, with variable results. Understanding the molecular mechanisms that regulate ACC proliferation could be useful to identify new therapeutic options. Sunitinib, a multitar...

Background: Von Hippel Lindau (VHL) disease is a rare tumour syndrome with a high penetrance. VHL mutation carriers develop numerous disease related manifestations in multiple organs during life, but precise difference in growth velocity and incidence of lesions in different organs is still unknown. We aimed to gain insight in the incidence of consecutive new disease manifestations in the organs of patients with VHL.Patients and methods: Clinical data in...

Context: Germline mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to head and neck paraganglioma (HNPGL), sympathetic PGL, phaeochromocytoma and renal cell carcinoma for which regular surveillance is required. SDHB-associated tumors harbor germline and somatic mutations, consistent with Knudson’s two-hit hypothesis stating that the combination of an inactivating germline mutation as a first hit and somatic loss of funct...