ECE2013 Poster Presentations Thyroid cancer (64 abstracts)
A novel multi-target pyrazolopyrimidine derivative with anti-neoplastic properties, CLM29, is active against medullary thyroid cancer in vitro and in vivo
Poupak Fallahi , Silvia Martina Ferrari , Guido Bocci , Concettina La Motta , Ilaria Ruffilli , Andrea Di Domenicantonio , Alda Corrado , Caterina Mancusi , Romano Danesi , Federico Da Settimo , Paolo Miccoli & Alessandro Antonelli
University of Pisa, Pisa, Italy.
Introduction: CLM29, a pyrazolo[3,4-d]pyrimidine compound, inhibits several targets (including the RET tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor and has an anti-angiogenic effect). Recently it has been shown to inhibit proliferation and migration in primary papillary dedifferentiated thyroid cancer cells. The aim of this study is to evaluate the anti-tumor activity of CLM29 in medullary thyroid cancer (MTC).
Methods/design: The CLM29 anti-proliferative and proapoptotic effects (5, 10, 30, 50 μmol/l) were tested in vitro in primary MTC (P-MTC) cells obtained at surgey, in TT cells harboring (C634W) RET mutation, and in human dermal microvascular endothelial cells (HMVEC-d). TT cells were injected in CD nu/nu mice which were treated with CLM29.
Results: CLM29 (10 μmol/l, 30 μmol/l or 50 μmol/l) inhibited significantly (P<0.001) the proliferation of P-MTC, or TT cells. CLM29 increased the percentage of apoptotic cells in TT and P-MTC cells dose-dependently (P<0.001), while had no effect on migration and invasion. CLM29 inhibited significantly the proliferation, blocking extracellular regulated kinase 1 and 2 phosphorylation and inducing apoptosis in HMVEC-d. The inhibition of proliferation by CLM29 was similar in P-MTC cells with/without RET mutation. TT cells were injected s.c. in CD nu/nu mice and tumor masses became detectable between 20 and 30 days after xenotransplantation. CLM29 (50 mg/kg per die) inhibited significantly tumor growth and weight and the therapeutic effect was significant from the 48th day after cell implantation (18 days after the beginning of treatment). A significant reduction of Ki-67 immunostaining and of microvessel density was observed in the CLM29-treated tumors.
Conclusion: The anti-tumor activity of a ‘pyrazolo[3,4-d]pyrimidine’ compound, CLM29, has been shown in MTC in vitro, and in vivo, opening the way to a future clinical evaluation.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more