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Igf-I influences everolimus activity in medullary thyroid carcinoma.

ABSTRACT: Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. It has been previously demonstrated that insulin-like growth factor I (IGF-I) protects MTC from the effects of antiproliferative drugs. Everolimus, an mTOR inhibitor, has shown potent antiproliferative effects in a human MTC cell line, TT, and in two human MTC primary cultures.To verify whether IGF-I may influence the effects of everolimus in a group of human MTC primary cultures.We collected 18 MTCs that were dispersed in primary cultures, treated without or with 10?nM-1??M everolimus and/or 50?nM IGF-I. Cell viability was evaluated after 48?h, and calcitonin (CT) secretion was assessed after a 6?h incubation. IGF-I receptor downstream signaling protein expression profile was also investigated.Everolimus significantly reduced cell viability in eight MTC [by ~20%; P?

SUBMITTER: Gentilin E

PROVIDER: S-EPMC4419838 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Igf-I influences everolimus activity in medullary thyroid carcinoma.

Gentilin Erica E Di Pasquale Carmelina C Rossi Martina M Tagliati Federico F Gagliano Teresa T Rossi Roberta R Pelizzo Mariarosa M Merante Boschin Isabella I Degli Uberti Ettore C EC Zatelli Maria Chiara MC

Frontiers in endocrinology 20150505

<h4>Context</h4>Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. It has been previously demonstrated that insulin-like growth factor I (IGF-I) protects MTC from the effects of antiproliferative drugs. Everolimus, an mTOR inhibitor, has shown potent antiproliferative effects in a human MTC cell line, TT, and in two human MTC primary cultures.<h4>Objective</h4>To verify whether IGF-I may influence the effects of everolimus in a group of human MTC p ...[more]

PMID: 25999915

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Project description:Multiple endocrine neoplasia type 2 is an autosomal dominant inherited syndrome caused by activating mutations in the RET proto-oncogene. The RETK666N DNA variant was previously reported in two isolated medullary thyroid carcinoma (MTC) cases, but no family studies are available, and its oncogenic significance remains unknown.The clinical features, genetic data, and family information of eight index MTC patients with a germline RETK666N variant were assessed.Four probands presented with MTC and extensive nodal metastasis, one with biopsy-confirmed distant metastasis. Two additional probands presented with localized disease. However, nodal status was not available. Of the final two probands, one had an incidental 1.5?mm MTC and C-cell hyperplasia uncovered after surgery for papillary thyroid carcinoma, and one had two foci of MTC (largest dimension 2.3?cm) detected after surgery for dysphagia. Genetic screening identified 16 additional family members carrying the K666N variant (aged 5-90 years), 11 of whom have documented evaluation for MTC. Of these, only two were found to have elevated basal serum calcitonin upon screening, and the remaining patients had calcitonin levels within the reference range. One patient who elected to have a thyroidectomy at 70 years of age was confirmed to have MTC. The other subject, 57 years old, elected surveillance. Four prophylactic thyroidectomies were performed, with one case of C-cell hyperplasia at 20 years and three cases that revealed normal pathology at ages 21, 30, and 30 years. None of the K666N DNA variant carriers had evidence of primary hyperparathyroidism or pheochromocytoma.From this case series, the largest such experience to date, it is concluded that the RETK666N variant is likely pathogenic and associated with low penetrance of MTC. However, the findings are insufficient to define its pathogenicity clearly and make firm recommendations for screening and treatment. Given the potential benefit associated with early detection of aberrant C-cell growth, and the noninvasive nature of genetic testing, "at risk" individuals should be screened, and if the K666N variant is identified, they should be managed using a personalized screening approach for detection of MTC.

Dataset Information

Igf-I influences everolimus activity in medullary thyroid carcinoma.

Publications

Igf-I influences everolimus activity in medullary thyroid carcinoma.

Similar Datasets

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