The role of T-type calcium channels in medullary thyroid carcinoma (MTC): T-type calcium channel blockers inhibit hormone secretion and induce apoptotic cell death in a human MTC cell line Abstract #160

Introduction: Medullary thyroid carcinoma (MTC) accounts for approximately 5-10% of thyroid cancers. In the case of tumors limited to the thyroid gland, the prognosis is generally favorable, whereas 5-year survival averages only 40% in patients with metastatic disease. In these patients, conventional chemotherapy only occasionally leads to a complete response and partial responses are observed in less than 30% of the cases. Therefore, intense efforts are currently directed toward the identification of new druggable targets for the treatment of this devastating disease.
Aim(s): To investigate whether drugs acting at voltage-gated T-type calcium channels could affect hormone release and/or cell proliferation in a prototypical MTC cell line, the human TT cells.
Materials and methods: The expression of the three cloned isoforms of T-type calcium channels (CaV3.1, CaV3.2 and CaV3.3) was evaluated by RT-PCR, whereby T-type currents were recorded by whole cell patch clamp electrophysiology. The effect of T-type calcium channel blockers (Ni2+, mibefradil and NNC 55-0396) on calcitonin secretion and cell proliferation/viability was evaluated respectively by measuring calcitonin levels with a chemiluminescent immunoassay system and the percentage of cell cycle arrest or apoptosis by flow cytometry.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr Rosario Pivonello

To read results and conclusion, please login ...

Further abstracts you may be interested in

#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
#201 Comparison of 18F-DOPA, 68Ga-Somatostatin Analogues and 18F-FDG PET-CT in Patients with Recurrent Medullary Thyroid Carcinoma
Introduction: Various PET tracers have been proposed for detection of recurrent disease in medullary thyroid carcinoma (MTC). No data have been reported comparing 18F-DOPA and 68Ga-somatostin analogues (SA) in MTC.
Conference: 8th Annual ENETS Conference (2011)
Category: Clinical
Presenting Author: Dr. Giorgio Treglia
#266 Everolimus Reduces Cell Viability in Selected Human Medullary Thyroid Carcinoma Primary Cultures
Introduction: It has been demonstrated that everolimus, an mTOR inhibitor, has a potent anti-proliferative effect in a human Medullary Thyroid Carcinoma (MTC) cell line, TT, and in two human MTC primary cultures.
Conference: 8th Annual ENETS Conference (2011)
Category: Clinical
Presenting Author: MD Maria Chiara Zatelli
#276 Mammalian Target of Rapamycin Pathway Activation is Associated with RET Mutation Status in Medullary Thyroid Carcinoma
Introduction: The genetic pathways involved in medullary thyroid carcinoma (MTC), except for RET mutations, are largely unknown, as well as the detailed expression mapping of intracellular signalling transducers.
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: MD Marco Volante
#333 Sporadic Hypercalcitoninemia: Thyroid Medullary carcinoma, Autoimmune Thyroiditis or GLP-1 Agonists’ Effect?
Introduction: Glucagon-like peptide 1 (GLP-1) receptor agonists’ stimulated C-cell hyperplasia and tumors in rodents, but not in humans. Calcitonin also increased in autoimmune thyroid disease.
Conference: 8th Annual ENETS Conference (2011)
Category: Clinical
Presenting Author: Dr. Raluca A. Trifanescu