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Growth inhibition of medullary thyroid carcinoma cells by pyrazolo-pyrimidine derivates

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Abstract

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 pyrazolo-pyrimidine 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 MZ-CRC-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.

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Authors and Affiliations

  1. Department of Clinical Sciences and Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza’, Rome

    R. Morisi, E. Tosi, E. Ferretti, C. Durante & S. Filetti

  2. Department of Pharmacobiological Sciences and Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, Catanzaro

    M. Celano, G. Costante, M. D’Agostino & D. Russo MD

  3. Department of Pharmaceutical Sciences, University of Genoa, Genoa

    S. Schenone & C. Brullo

  4. Pharmacobiological Department, University of Messina and IRCCS Centro Neurolesi ‘Bonino Pulejo’, Messina

    M. Navarra

  5. Pharmacochemical-technological Department, University of Siena, Siena, Italy

    G. Botta & M. Botta

Authors
  1. R. Morisi
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  2. M. Celano
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  3. E. Tosi
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  4. S. Schenone
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  5. M. Navarra
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  6. E. Ferretti
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  7. G. Costante
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  8. C. Durante
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  9. G. Botta
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  10. M. D’Agostino
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  11. C. Brullo
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  12. S. Filetti
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  13. M. Botta
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  14. D. Russo MD
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Corresponding author

Correspondence to D. Russo MD.

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Morisi, R., Celano, M., Tosi, E. et al. Growth inhibition of medullary thyroid carcinoma cells by pyrazolo-pyrimidine derivates. J Endocrinol Invest 30, RC31–RC34 (2007). https://doi.org/10.1007/BF03349220

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  • DOI: https://doi.org/10.1007/BF03349220

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