CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity in medullary thyroid cancer in vitro and in vivo

被引：21

作者：

Antonelli, Alessandro ^{[1
]}

Bocci, Guido ^{[1
,2
]}

La Motta, Concettina ^{[3
]}

Ferrari, Silvia Martina ^{[1
]}

Fallahi, Poupak ^{[1
]}

Corrado, Alda ^{[1
]}

Fioravanti, Anna ^{[1
]}

Sartini, Stefania ^{[3
]}

Orlandi, Paola ^{[1
]}

Piaggi, Simona ^{[4
]}

Corti, Alessandro ^{[4
]}

Materazzi, Gabriele ^{[5
]}

Galleri, David ^{[5
]}

Ulisse, Salvatore ^{[6
]}

Fontanini, Gabriella ^{[5
]}

Danesi, Romano ^{[1
]}

Da Settimo, Federico ^{[3
]}

Miccoli, Paolo ^{[5
]}

机构：

[1] Univ Pisa, Dept Clin & Expt Med, I-56126 Pisa, Italy

[2] Ist Toscano Tumori, Florence, Italy

[3] Univ Pisa, Dept Pharm, I-56126 Pisa, Italy

[4] Univ Pisa, Dept Translat Res & New Technol Med & Surg, I-56126 Pisa, Italy

[5] Univ Pisa, Dept Surg Med Mol Pathol & Crit Area, I-56126 Pisa, Italy

[6] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2014年 / 393卷 / 1-2期

关键词：

Tyrosine kinase inhibitors; Pyrazolo[3,4-d]pyrimidine; CLM29; Medullary thyroid cancer; Thyroid cancer; TYROSINE KINASE INHIBITOR; CELL-PROLIFERATION; ONCOGENIC RET; CARCINOMA; THIAZOLIDINEDIONES; COMBINATION; MECHANISMS; THERAPIES;

D O I：

10.1016/j.mce.2014.06.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

CLM29 (a pyrazolo[3,4-d]pyrimidine, that inhibits RET, epidermal growth factor receptor, vascular endothelial growth factor receptor, and has an anti-angiogenic activity) has anti-neoplastic activity in papillary dedifferentiated thyroid cancer. Here we tested CLM29 in medullary thyroid cancer (MTC), in primary MTC cells (P-MTC) obtained at surgery, and in TT cells harboring (C634 W) RET mutation. CLM29 (10, 30, 50 mu M) inhibited significantly (P < 0.001) the proliferation, and increased the percentage of apoptotic P-MTC, TT and human dermal microvascular endothelial cells. The inhibition of proliferation by CLM29 was similar in P-MTC cells with/without RET mutation. TT cells were injected sc in CD nu/nu mice, and tumor masses became detectable between 20 and 30 days after xenotransplantation; CLM29 (50 mg/kg/die) reduced significantly tumor growth and weight, and microvessel density. The anti-tumor activity of CLM29 has been shown in MTC in vitro, and in vivo, opening the way to a future clinical evaluation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：56 / 64

页数：9

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