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尼罗替尼和伊马替尼在新建立的异种移植模型中对人嗜酸性粒细胞白血病细胞的生长具有相当的抑制作用。

Nilotinib and imatinib are comparably effective in reducing growth of human eosinophil leukemia cells in a newly established xenograft model.

机构信息

Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical-Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

PLoS One. 2012;7(2):e30567. doi: 10.1371/journal.pone.0030567. Epub 2012 Feb 14.

Abstract

We developed a xenograft model of human Chronic Eosinophilic Leukemia (CEL) to study disease progression and remission-induction under therapy with tyrosine kinase inhibitors using imatinib and nilotinib as examples. The FIP1L1/PDGFRA+ human CEL cell lineEOL-1 was injected intravenously into scid mice, and MR imaging and FACS analysis of mouse blood samples were performed to monitor disease development and the effects of imatinib and nilotinib. Organ infiltration was analyzed in detail by immunohistochemistry after sacrifice. All animals developed CEL and within one week of therapy, complete remissions were seen with both imatinib and nilotinib, resulting in reduced total tumor volumes by MR-imaging and almost complete disappearance of EOL-1 cells in the peripheral blood and in tissues. The new model system is feasible for the evaluation of new tyrosine kinase inhibitors and our data suggest that nilotinib may be a valuable additional targeted drug active in patients with FIP1L1/PDGFRA+ CEL.

摘要

我们建立了人慢性嗜酸性白血病(CEL)的异种移植模型,以研究使用伊马替尼和尼罗替尼作为范例的酪氨酸激酶抑制剂治疗下疾病的进展和缓解诱导。将 FIP1L1/PDGFRA+人 CEL 细胞系 EOL-1 静脉内注射到 scid 小鼠中,并进行 MR 成像和小鼠血液样本的 FACS 分析,以监测疾病的发展以及伊马替尼和尼罗替尼的作用。在处死动物后通过免疫组织化学详细分析器官浸润。所有动物均发生 CEL,在治疗的一周内,伊马替尼和尼罗替尼均出现完全缓解,MR 成像显示总肿瘤体积减少,外周血和组织中 EOL-1 细胞几乎完全消失。新的模型系统可用于评估新的酪氨酸激酶抑制剂,并且我们的数据表明尼罗替尼可能是 FIP1L1/PDGFRA+CEL 患者中一种有价值的附加靶向药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/3279340/64747f3715de/pone.0030567.g001.jpg

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