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A systematic comparison of anti-angiogenesis efficacy and cardiotoxicity of receptor tyrosine kinase inhibitors in zebrafish model.
Ma, Cui; Wu, Zhenghua; Wang, Xue; Huang, Mengling; Wei, Xiaona; Wang, Wei; Qu, Han; Qiaolongbatu, Xijier; Lou, Yuefen; Jing, Lili; Fan, Guorong.
Afiliación
  • Ma C; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China; Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, PR China.
  • Wu Z; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China; Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, PR China.
  • Wang X; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China.
  • Huang M; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China.
  • Wei X; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China.
  • Wang W; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China.
  • Qu H; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China; Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, PR China.
  • Qiaolongbatu X; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China; Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, PR China.
  • Lou Y; Department of Pharmacy, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200434, PR China. Electronic address: louyuefen@sina.cn.
  • Jing L; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China. Electronic address: lilijing@sjtu.edu.cn.
  • Fan G; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai 200240, PR China; Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, PR China. Electronic address: fanguorong@sjtu.edu.cn.
Toxicol Appl Pharmacol ; 450: 116162, 2022 09 01.
Article en En | MEDLINE | ID: mdl-35830948
Pathological angiogenesis is fundamental to progression of cancerous tumors and blinding eye diseases. Anti-angiogenic receptor tyrosine kinase inhibitors (TKIs) are in broad use for the treatment of these diseases. With more and more TKIs available, it is a challenge to make an optimal choice. It remains unclear whether TKIs demonstrate similar anti-angiogenesis activities in different tissues. Many TKIs have shown varying degrees of toxic effects that should also be considered in clinical use. This study investigates the anti-angiogenic effects of 13 FDA-approved TKIs on the intersegmental vessels (ISVs), subintestinal vessels (SIVs) and retinal vasculature in zebrafish embryos. The results show that vascular endothelial growth factor receptor TKIs (VEGFR-TKIs) exhibit anti-angiogenic abilities similarly on ISVs and SIVs, and their efficacy is consistent with their IC50 values against VEGFR2. In addition, VEGFR-TKIs selectively induces the apoptosis of endothelial cells in immature vessels. Among all TKIs tested, axitinib demonstrates a strong inhibition on retinal neovascularization at a low dose that do not strongly affect ISVs and SIVs, supporting its potential application for retinal diseases. Zebrafish embryos demonstrate cardiotoxicity after VEGFR-TKIs treatment, and ponatinib and sorafenib show a narrow therapeutic window, suggesting that these two drugs may need to be dosed more carefully in patients. We propose that zebrafish is an ideal model for studying in vivo antiangiogenic efficacy and cardiotoxicity of TKIs.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pez Cebra / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pez Cebra / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2022 Tipo del documento: Article