Endocrine Abstracts

Pheochromocytomas (PHEO) and paragangliomas (PGL) are neuroendocrine tumors that were born to be imaged using specific radiopharmaceuticals. This is based on the expression of the cell membrane norepinephrine transporter system and somatostatin receptors, as well as GLUT and amino acid transporters found on PHEO/PGL cells.Anatomical imaging modalities (e.g. CT or MRI) may define the size, shape, structure and enhancement of tumors well, but they lack the...

Endocrine tumors differ from other tumors in that that they use specific pathways to synthesize, store, and release hormones, their metabolites, or precursors; these tumors may differentially express specific receptors or transporters located in either the cell membrane or intracellular space. Additionally, they can uptake released hormones back into their cells. These characteristics allow for the existence of several (neuro)endocrine, tumor-specific markers that can be used ...

Mutations in the mitochondrial succinate dehydrogenase (SDH) subunits A, B, C, and D have been shown to hamper oxidative phosphorylation and predispose to pheochromocytomas (PHEOs) and paragangliomas (PGLs). These tumors are characterized by a glycolytic and pseudohypoxic phenotype, which is also seen in most PHEOs/PGLs occurring as part of von Hippel–Lindau (VHL) syndrome, due to VHL gene mutations. The rate of extra-adrenal tumor origin and malignancy however is particu...

This study examined whether different forms of hereditary pheochromocytoma are characterized by different catecholamine phenotypes and whether this is reflected by differences in plasma concentrations of normetanephrine, metanephrine and methoxytyramine – the respective O-methylated metabolites of norepinephrine, epinephrine and dopamine. Subjects included 154 patients with hereditary pheochromocytoma, 72 with tumors associated with von Hippel–Lindau (VHL) syndrome, ...

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors. About 30-40% of Pheo/PGLs are due to a germ-line mutation in one of the 13 main susceptibility genes which include the genes encoding the four subunits of the succinate dehydrogenase (SDH - mitochondrial complex II). In PHEO/PGL due to SDHB mutations up to 80% of affected patients develop metastatic disease and no successful cure is at present available. To obtain an experimental model resembli...

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors. About 30–40% of Pheo/PGLs are due to a germ-line mutation in one of the 13 main susceptibility genes which include the genes encoding the four subunits of the succinate dehydrogenase (SDH - mitochondrial complex II). In PHEO/PGL due to SDHB mutations up to 80% of affected patients develop metastatic disease and no successful cure is at present available. Tumor microenvironment plays a pivo...

Paragangliomas are rare neuroendocrine tumors derived from neural crest cells: if localized in the adrenal medulla they are called Pheocromocytomas (Pheo).The 30–40% of Pheo are mutated in one of the susceptibility genes among which there are genes encoding for the four subunits of the succinate dehydrogenase (SDH). Germ line mutations of SDHB are metastatic in about 80% of the cases. Surgery is the current therapy, but in presence of metastasis there is no effective trea...

Introduction: In our previous studies we found that the combination of 13-cis retinoic acid (13cRA) and lovastatin significantly reduced tumour growth in a mouse phaeochromocytoma allograft model, with the lowest microvessel density in the combination-treated tumours. We have now investigated the effect of 13cRA plus lovastatin on neuroendocrine (BON1, H727) and non-endocrine tumour (HepG2, Huh7) cell viability and signalling pathways (EGFR, AKT, ERK, p70S6K) to eluci...

Background: Patients with advanced pheochromocytoma/paraganglioma (PPGL) or pancreatic neuroendocrine tumor (panNET) are in need of novel targeted therapies. Hypoxia-inducible factor 2α (HIF-2α) is one of the key oncogenic drivers in neuroendocrine tumors. Hypoxia signaling pathway alterations or other mechanisms that stabilize HIFs are common in some PPGLs and panNETs. Belzutifan (MK-6482), a HIF-2α inhibitor, has shown antitumor activity in advanced renal cell...

Background: GI neuroendocrine tumors express somatostatin (SSTR) receptors, and the radioloabeled SSTR analog Lu-177-DOTATATE is an FDA-approved systemic treatment for those with metastatic disease. Olaparib is a poly (ADP-ribose) polymerase inhibitor (PARPi) which inhibits cells from repairing damaged DNA, especially single-stranded DNA breaks caused by beta particle emissions from the radioactive decay of Lu-177. We report the first results of a phase 1/2 study evaluating th...