CLM29 (a pyrazolo[3,4-d]pyrimidine, that inhibits RET, epidermal growth factor receptor, vascular endothelial growth factor receptor, and has an anti-angiogenic activity) has anti-neoplastic activity in papillary dedifferentiated thyroid cancer. Here we tested CLM29 in medullary thyroid cancer (MTC), in primary MTC cells (P-MTC) obtained at surgery, and in TT cells harboring (C634W) RET mutation. CLM29 (10, 30, 50 μM) inhibited significantly (P<0.001) the proliferation, and increased the percentage of apoptotic P-MTC, TT and human dermal microvascular endothelial cells. The inhibition of proliferation by CLM29 was similar in P-MTC cells with/without RET mutation. TT cells were injected sc in CD nu/nu mice, and tumor masses became detectable between 20 and 30 days after xenotransplantation; CLM29 (50mg/kg/die) reduced significantly tumor growth and weight, and microvessel density. The anti-tumor activity of CLM29 has been shown in MTC in vitro, and in vivo, opening the way to a future clinical evaluation.

CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity in medullary thyroid cancer in vitro and in vivo

ANTONELLI, ALESSANDRO;BOCCI, GUIDO;LA MOTTA, CONCETTINA;Ferrari SM;Fallahi P;FIORAVANTI, ANNA;SARTINI, STEFANIA;ORLANDI, PAOLA;CORTI, ALESSANDRO;MATERAZZI, GABRIELE;FONTANINI, GABRIELLA;DANESI, ROMANO;DA SETTIMO PASSETTI, FEDERICO;MICCOLI, PAOLO
2014-01-01

Abstract

CLM29 (a pyrazolo[3,4-d]pyrimidine, that inhibits RET, epidermal growth factor receptor, vascular endothelial growth factor receptor, and has an anti-angiogenic activity) has anti-neoplastic activity in papillary dedifferentiated thyroid cancer. Here we tested CLM29 in medullary thyroid cancer (MTC), in primary MTC cells (P-MTC) obtained at surgery, and in TT cells harboring (C634W) RET mutation. CLM29 (10, 30, 50 μM) inhibited significantly (P<0.001) the proliferation, and increased the percentage of apoptotic P-MTC, TT and human dermal microvascular endothelial cells. The inhibition of proliferation by CLM29 was similar in P-MTC cells with/without RET mutation. TT cells were injected sc in CD nu/nu mice, and tumor masses became detectable between 20 and 30 days after xenotransplantation; CLM29 (50mg/kg/die) reduced significantly tumor growth and weight, and microvessel density. The anti-tumor activity of CLM29 has been shown in MTC in vitro, and in vivo, opening the way to a future clinical evaluation.
Antonelli, Alessandro; Bocci, Guido; LA MOTTA, Concettina; Ferrari, Sm; Fallahi, P; Corrado, A; Fioravanti, Anna; Sartini, Stefania; Orlandi, Paola; Piaggi, S; Corti, Alessandro; Materazzi, Gabriele; Galleri, D; Ulisse, S; Fontanini, Gabriella; Danesi, Romano; DA SETTIMO PASSETTI, Federico; Miccoli, Paolo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/565267
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