Details

Autor(en) / Beteiligte

• Antonelli, Alessandro
• Bocci, Guido
• La Motta, Concettina
• Ferrari, Silvia Martina
• Fallahi, Poupak
• Ruffilli, Ilaria
• Di Domenicantonio, Andrea
• Fioravanti, Anna
• Sartini, Stefania
• Minuto, Michele
• Piaggi, Simona
• Corti, Alessandro
• Alì, Greta
• Di Desidero, Teresa
• Berti, Piero
• Fontanini, Gabriella
• Danesi, Romano
• Da Settimo, Federico
• Miccoli, Paolo

Titel

CLM94, a Novel Cyclic Amide with Anti-VEGFR-2 and Antiangiogenic Properties, Is Active against Primary Anaplastic Thyroid Cancer in Vitro and in Vivo

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2012-04, Vol.97 (4), p.E528-E536

Ort / Verlag

United States: Endocrine Society

Erscheinungsjahr

2012

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Context and Objective: We have studied the antitumor activity of a novel cyclic amide, CLM94, with anti-vascular endothelial growth factor (VEGF) receptor-2 and antiangiogenic activity in primary anaplastic thyroid cancer (ATC) cells in vitro and in vivo. Design and Main Outcome Measures: CLM94 was tested: 1) in two human cell lines (HMVEC-d, dermal microvascular endothelial cells; and 8305C, undifferentiated thyroid cancer) at 0.001–100 μm; 2) in ATC cells at the concentrations of 10, 30, and 50 μm; and 3) in an ATC cell line (AF) in CD nu/nu mice. Results: CLM94 significantly inhibited VEGF receptor-2 and epidermal growth factor receptor phosphorylation in HMVEC-d and proliferation in HMVEC-d and 8305C cells. 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 μm 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 d afterward. CLM94 (40 mg/kg · d) significantly inhibited tumor growth (starting 10 d 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 tumor tissues. Conclusions: The antitumor and antiangiogenic activity of a new “cyclic amide” compound, CLM94, is very promising in ATC, opening the way to a future clinical evaluation.