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Endocrine Abstracts (2012) 29 P1780

ICEECE2012 Poster Presentations Thyroid cancer (108 abstracts)

CLM94, a novel cyclic amide with anti-VEGFR-2 and antiangiogenic properties, is active against primary anaplastic thyroid cancer in vitro and in vivo

A. Antonelli , G. Bocci , C. La Motta , S. Ferrari , P. Fallahi , I. Ruffilli , A. Di Domenicantonio , F. Da Settimo & P. Miccoli


University of Pisa, Pisa, Italy.


Introduction: The antitumor activity of a novel cyclic amide, CLM94, with anti-VEGFR-2 and antiangiogenic activity, in primary anaplastic thyroid cancer (ATC) cells in vitro and in vivo, has been studied.

Design and Methods: CLM94 was tested: i) in two human cell lines (HMVEC-d, dermal microvascular endothelial cells; 8305C, undifferentiated thyroid cancer) at 0.001–100 mcM; ii) in ATC cells at the concentrations of 10, 30, 50 mcM; iii) in a ATC-cell line (AF) in CD nu/nu mice.

Results: CLM94 significantly inhibited VEGFR-2 and EGFR phosphorylation in HMVEC-d, and proliferation in HMVEC-d and 8305C cell. A significant reduction of proliferation with CLM94 in ATC cells (P<0.01, ANOVA) and a slight but significant reduction of proliferation with CLM94 30 and 50 mcM in normal thyroid follicular cells (P<0.01, ANOVA) were shown. CLM94 increased the percentage of apoptotic ATC cells dose-dependently (P<0.001, ANOVA) and inhibited migration (P<0.01) and invasion (P<0.001). AF-cell line was injected sc in CD nu/nu mice and tumor masses became detectable 25 days after. CLM94 (40 mg/kg/die) inhibited significantly tumor growth (starting 10 days after the beginning of treatment). CLM94 significantly decreased the VEGF-A gene expression in the AF cell line and the VEGF-A protein and microvessel density in AF tumour tissues.

Conclusions: The antitumor and antiangiogenic activity of a new ‘cyclic amide’ compound CLM94 is very promising in anaplastic thyroid cancer, opening the way to a future clinical evaluation.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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