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 (C634. W) 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 (50. mg/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. © 2014 Elsevier Ireland Ltd.
CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity in medullary thyroid cancer in vitro and in vivo / Alessandro, Antonelli; Guido, Bocci; Concettina La, Motta; Silvia Martina, Ferrari; Poupak, Fallahi; Corrado, Alda; Anna, Fioravanti; Stefania, Sartini; Paola, Orlandi; Simona, Piaggi; Alessandro, Corti; Gabriele, Materazzi; David, Galleri; Ulisse, Salvatore; Gabriella, Fontanini; Danesi, Romano; Federico Da, Settimo; Paolo, Miccoli. - In: MOLECULAR AND CELLULAR ENDOCRINOLOGY. - ISSN 0303-7207. - STAMPA. - 393:1-2(2014), pp. 56-64. [10.1016/j.mce.2014.06.002]
CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity in medullary thyroid cancer in vitro and in vivo
ULISSE, SALVATORE;
2014
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 (C634. W) 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 (50. mg/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. © 2014 Elsevier Ireland Ltd.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
