Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 EP867 | DOI: 10.1530/endoabs.37.EP867

ECE2015 Eposter Presentations Thyroid cancer (90 abstracts)

The two tyrosine kinase inhibitors, CLM29 and CLM3, have antineoplastic activity in primary cultures from anaplastic thyroid cancer obtained from fine needle aspiration

Silvia Martina Ferrari 1 , Poupak Fallahi 1 , Concettina La Motta 2 , Gabriele Materazzi 3 , Francesca Ragusa 1 , Francesca Limongi 1 , Ilaria Ruffilli 1 , Federico Da Settimo 2 , Paolo Miccoli 3 & Alessandro Antonelli 1


1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Pharmacy, University of Pisa, Pisa, Italy; 3Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.


Anaplastic thyroid cancer (ATC) is one of the most lethal endocrine malignancy, with a mean survival of about 6 months. Until now, the most effective therapy for ATC comprises a multimodal treatment protocol, including surgery, chemotherapy (doxorubicin and cisplatin), and hyperfractionated accelerated external beam radiotherapy, with a median patient survival of 10 months. A possible increase in the effectiveness of the treatment could be achieved testing the sensitivity of ‘primary anaplastic thyroid cancer cells’ (pATC) from each subject to different drugs, in this way avoiding the administration of inactive therapeutics to these patients. Here, we tested the in vitro antineoplastic effect of the two new ‘pyrazolo (3,4-d) pyrimidine’ compounds (CLM3, CLM29) in pATC obtained both from biopsy (biop-pATC), or from fine needle aspiration (FNA-pATC), from five patients. We evaluated different concentrations of both compounds (1, 10, 30, and 50 μM). A significant reduction of proliferation was evidenced in FNA-pATC, or biop-pATC, cells by WST-1 assay (a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, used in the MTT assay) with respect to the control, especially with CLM29, while slightly with CLM3. Furthermore the percentage of apoptotic cells in FNA-pATC, or biop-pATC, cells was increased dose-dependently by both compounds. Our results show no significant differences in sensitivity to CLM29 or CLM3 between the tested ATC cells from FNA, or biopsy.We conclude that: 1) primary FNA-pATC cells have a sensitivity to tyrosine kinase inhibitors (TKIs) agents quite similar to that observed in biop-pATC cells, and for this reason the use of primary FNA-pATC cells to conduct the in vitro tests could reduce the time needed for biopsy; 2) CLM29 and CLM3 reduce cell growth, increasing the percentage of apoptotic cells in ATC; 3) the possibility to test sensitivity to different TKIs in each patient could increase the efficacy of treatments, avoiding the administration of ineffective drugs.

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