Endocrine Abstracts

The vault complex, consisting of a major vault protein (MVP), two minor vault proteins (VPARP and TEP1) and small untranslated RNA molecules (vault RNAs 1–4), is considered the largest intracellular ribonucleoprotein particle. Although in recent years, vaults were believed to be involved in multidrug resistance, the exact function of this complex has remained unclear. Recently, we investigated the therapeutic applicability of a Tumour-Vascular-Disrupting Agent (ASA) in pr...

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...

Medical treatment of adrenocortical carcinoma (ACC) is limited to common cytotoxic agents, which are usually given in combination with mitotane (M). Recently, we investigated together with M the effects of i) the classical EDP protocol (etoposide, doxorubicin, and cisplatin) and ii) a novel paclitaxel containing scheme PDP (paclitaxel, doxorubicin, and cisplatin) on human NCIh295 cells indicating anti-tumoral superiority of PDP-M over EDP-M regarding cell viability (P...

Vascular disrupting agents (VDAs) differ from angiogenesis inhibitors by attacking established tumor blood vessels rather than preventing growth of new ones. We investigated effects of the tumor-VDA ASA404 against neuroendocrine tumors of the gastroenteropancreatic system (GEP-NETs) and adrenocortical carcinoma (ACC) 24 h after treatment of BON and NCIh295 tumor bearing mice with ASA404 (A), paclitaxel (P) or the combined administration (A+P). A significant decrease in cell pr...

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...

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 ...

Only two human cell lines are available for adrenocortical carcinoma (ACC) which do not reflect the functional heterogeneity of individual patient tumors and metastases. To overcome the lack of preclinical models for testing of novel therapeutic options in recent years we aimed at the development of patient-individual tumor models for endocrine tumors. Therefore, pieces of surgically excised patient tumors were implanted subcutaneously in the neck of athymic nude mice. To inve...

ASA404 (Vadimezan) belongs to a class of agents with disrupting properties against tumor vasculature. Herein, putative therapeutic applicability was investigated in preclinical models for neuroendocrine tumors of the gastroenteropancreatic system (BON) and adrenocortical carcinoma (NCIh295). Upon treatment of tumor bearing mice we detected a significant disruption of microvessels, decrease in cell proliferation, increase of apoptotic cells and extensive necrosis in BON tumors ...

In an attempt to amend the lack of preclinical models for endocrine tumors, we recently initiated establishment of patient-individual tumor models. Pieces from four adrenocortical carcinomas (ACC), one aldosterone producing adenoma (APA), one pheochromocytoma (pheo), one metastasis of a malignant pheo, one pheo and medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 and 11 neuroendocrine tumors (NETs, nine NETs of the gastroenteropancreatic system i...