Endocrine Abstracts

Current systemic treatments are not satisfying for the treatment of adrenocortical carcinoma (ACC). However, translation of preclinically promising approaches were often disappointing indicating that existing tumor models might have inadequately predicted clinical applicability. Thus, our workgroup initiated a comparative drug screen of relevant chemotherapies and therapies targeting IGFR, EGFR, VEGFR/PDGFR and Wnt signalling pathway in the classical NCI-H295R and recently dev...

In an attempt, to overcome the lack of preclinical models for adrenocortical carcinoma (ACC), we recently aimed at the development of patient-individual tumor models for ACC. During these studies one xenograft (MUC-1), derived from a neck metastasis of an ACC, showed extraordinary engraftment properties and sustained tumor growth over several passages in the murine host. During ongoing studies we investigated and compared all currently available xenograft models for ACC (NCI-H...

Bone morphogenic proteins (BMPs) have been demonstrated to impact tumorigenesis in a variety of tumors. As for the adrenal cortex, BMP6 has been implicated as an important modulator of aldosterone secretion. To screen for alterations of BMP dependent pathways in adrenal tumorigenesis we performed gene profiling experiments. By comparing human adrenal carcinoma (ACC) against normal adrenal glands (Co) we detected a down-regulation of various BMPs (e.g. BMP2, BMP5) which was fur...

The adrenal gland displays an important role in integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. The adrenal is the central organ of the stress response system, responsible for responses to acute and chronic stress stimuli and, thereby, playing a major role in numerous stress-related disorders. While for other diseases translational scientists developed programs to generate healthy cells to regenerate damaged tissues in pati...

To date, the in depth analysis of the key molecular mechanisms involved in functional autonomy and tumor formation in aldosterone producing adenomas has been hampered by the rarity of the disease and the lack of adequate tumor cell lines. Herein, we cultivated a primary cell culture of an aldosterone producing adenoma taken from a 40 year old male patient with a left sided adrenal tumor mass. The cells have been passaged 24 times and still continue to grow after nearly 11 mont...

Radioactive and transgenic tracing experiments indicate that in the adult adrenal stem cells persist in the periphery of the cortex, which migrate centripetally and populate the inner cortical zones upon differentiation. However, investigation of these cells has been hampered by the lack of known marker genes. Vital Hoechst dye exclusion has been described as a method for isolating a side population (SP) from mouse bone marrow, which was enriched with stem cells. Utilizing thi...

Current systemic treatment options for patients with ACCs are far from being satisfactory. DNA damage/repair mechanisms, which involve e.g. ATM/ATR-signalling or RRM1/RRM2 encoded ribonucleotide reductase (RNR) activation commonly contribute to drug resistance. Moreover, also the regulation of RRM2b, the p53-induced alternative to RRM2, is of unclear importance for ACC. Upon extensive drug screening, including a large panel of classical chemotherapies (doxorubicin, etoposide, ...