Expression of IGF/mTOR Pathway Components in Human Pheochromocytomas and In Vitro Inhibition of PC12 Rat Pheochromocytoma Cell Growth by mTOR Inhibitors Abstract #269

Introduction: The pathogenesis of pheochromocytomas (pheo) is poorly understood and malignant pheo need new treatment options. mTOR inhibitors, as sirolimus(S) and everolimus(E), are promising antineoplastic drugs.
Aim(s): To evaluate whether the IGF/mTOR pathways have a role in the pathogenesis and whether S and E may have antiproliferative effects in pheo.
Materials and methods: In 24 human pheo and two normal adrenal medulla (NM), we evaluated the mRNA expression of: IGFI, IGFII, IGF-I-Receptor [IGF-R], Insulin-Receptor[IR]A, IRB, IGF-IIR, IGF-Binding-Proteins [BP] 1, 2, 3 and 6, mTOR, 4EBP1 and p70S6K (by qPCR). We tested the dose- and time-dependent effects of S and E on cell growth in the PC12 rat pheo cell line.
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: MD Maria Cristina De Martino

To read results and conclusion, please login ...

Further abstracts you may be interested in

#19 Antitumor activity of Pasireotide (SOM230) alone and in combination with Everolimus (RAD001) in DU-145 human prostate cancer model
Introduction: Pasireotide (SOM230) is a novel multi-receptor ligand somatostatin analogue with high affinity for somatostatin receptor subtypes sst1,2,3 and sst5. Like octreotide, which binds primarily to sst2, it inhibits hypersecretion of hormones from patients with functional pituitary tumors and gastroenteropancreatic neuroendocrine (GEP/NET) tumors. In addition, tumor shrinkage has been observed with both compounds in patients with acromegaly, Cushing’s disease and GEP/NETs, but its tumor-reducing mechanism of action has so far not been revealed. In patients with breast and liver cancer, octreotide had little or no antitumor activity.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr. Herbert A. Schmid
#38 Expression of mTOR signaling pathway and effects of mTOR inhibitors on its pathway in human neuroendocrine tumors
Introduction: Neuroendocrine tumors (NET), especially well-differentiated endocrine tumors, are often slow-growing, indolent, and may not become clinically apparent until the manifestations of metastatic spread or carcinoid syndrome. Results of previous studies demonstrated that phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway may be activated in the great majority of NET cells. mTOR inhibitors are therefore considered effective anti-tumor reagents but they may also induce an activation of PI3K/Akt and MAPK pathways as a compensatory action and reduce their own anti-tumor activities.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Professor Hironobu Sasano
Authors: Iida S, Miki Y, Ono K, Sasano H
#48 Preliminary report of the use of everolimus in a patient with progressive medullary thyroid carcinoma
Introduction: Medullary thyroid carcinoma (MTC) accounts for about 5-10% of all thyroid cancers, and while disease localized to the thyroid can be cured by surgery, there is no effective treatment for disseminated MTC. Constitutive activation of the RET proto-oncogene is implicated in familial and a proportion of sporadic cases, and up-regulates the AKT/PI3-kinase/mTOR signal transduction pathway. Recent studies have shown that the inhibitor of mTOR, everolimus (RAD001, Novartis, Basel), can inhibit the proliferation of the TT cell line and human MTC tumor cells in vitro. Clinically, everolimus has been shown to attenuate the progression of some gastrointestinal neuroendocrine tumors, but its clinical use in MTC has not yet been evaluated.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr Maralyn R Druce
#59 Incidence and clinical significance of adrenal masses in patients with gastrenteropancreatic neuroendocrine tumors
Introduction: The widespread application of modern imaging modalities, mainly computerized tomography (CT) and magnetic resonance imaging (MRI), has revealed a 2-3% incidence of inadvertently discovered adrenal masses, the majority of which are non-functioning benign adrenal adenomas. In the presence of a known malignancy, such lesions have a more than 30% incidence of being metastases. As patients with gastrenteropancreatic neuroendocrine tumors (GEP-NETS) have mainly well-differentiated and slow-growing tumors and are subject to routine abdominal imaging for disease staging or during follow-up, it is important to study the incidence and significance of such lesions based on the recently introduced TNM classification system.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr Georgios Kanakis
#96 Expression of components of the mTOR pathway in gastroenteropancreatic neuroendocrine tumors
Introduction: Recently, the mammalian target of rapamycin (mTOR) inhibitors have entered late phase clinical trials in a broad variety of solid human malignancies, including neuroendocrine tumors (NETs). Since these drugs will certainly be used as routine therapeutics in the near future, it is surprising that information on the exact expression patterns of mTOR and its downstream target 4EBP1 in NETs is still lacking.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Atsuko Kasajima