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Title: Growth inhibition of medullary thyroid carcinoma cells by pyrazolo-pyrimidine derivatives
Authors: R., Morisi
M., Celano
E., Tosi
S., Schenone
M., Navarra
E., Ferretti
G., Costante
C., Durante
G., Botta
M., D'Agostino
C., Brullo
S., Filetti
Botta, Maurizio 
D., Russo
Issue Date: 2007
Project: None 
There is no effective treatment for recurrent or metastatic medullary thyroid carcinoma (MTC), a tumor arising from thyroid C-cells commonly presenting an inherited or acquired RET mutation. In this study we examined the sensitivity of two human MTC cell lines to novel pyrazolopyrimidine derivates, able to inhibit src-family tyrosine kinase activity. In TT cells [carrying the multiple endocrine neoplasia (MEN)2A Ret mutation Cys 634Trp] and MZ-CRC-1 cells (carrying the MEN2B RET mutation Met891Thr), one of these compounds, namely Si 34, determined a significant growth inhibitory effect (approximately 90% vs control for TT, 80% vs control for MZ-CRC-1) mainly due to enhanced cell mortality after a 6-day incubation. At concentrations that increased cell mortality, neither biochemical or morphological characteristics of apoptosis were detected in TT and MZCRC- 1 cells treated with Si 34. These results, when confirmed in other in vivo preclinical models, suggest that this novel tyrosine kinase inhibitor may be useful for the treatment of MTC.
ISSN: 0391-4097
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