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)
Presenting Author: Dr Rosario Pivonello
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