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肿瘤细胞中促红细胞生成素受体表达的临床前研究:对使用促红细胞生成蛋白纠正癌症相关贫血临床应用的影响

Preclinical studies of erythropoietin receptor expression in tumour cells: impact on clinical use of erythropoietic proteins to correct cancer-related anaemia.

作者信息

Osterborg Anders, Aapro Matti, Cornes Paul, Haselbeck Anton, Hayward Colin R W, Jelkmann Wolfgang

机构信息

Department of Oncology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.

出版信息

Eur J Cancer. 2007 Feb;43(3):510-9. doi: 10.1016/j.ejca.2006.10.012. Epub 2006 Dec 5.

Abstract

In vitro and animal model studies have shown erythropoietin receptor (Epo-R) mRNA and/or protein may be present in a range of human tumours and cancer cell lines, and erythropoiesis-stimulating agents (ESAs) have been reported to have tumour cell growth-modulating effects. Following a review of the literature, we conclude that considerations must be made when interpreting data from the preclinical studies. First, supraphysiological doses of ESAs were usually used. Second, there are no well validated, commercially available antibodies for identifying the presence and functionality of Epo-R at the protein level, either intracellularly or on the cell surface. Data from previous studies that used antibodies only for Epo-R detection must therefore be interpreted with caution. Together with diverging results in the literature, these methodological limitations indicate that findings from preclinical studies must not be over-translated in terms of their clinical relevance to patients with cancer.

摘要

体外和动物模型研究表明,促红细胞生成素受体(Epo - R)mRNA和/或蛋白质可能存在于一系列人类肿瘤和癌细胞系中,并且据报道促红细胞生成素(ESAs)具有肿瘤细胞生长调节作用。在回顾文献后,我们得出结论,在解释临床前研究数据时必须加以考虑。首先,通常使用超生理剂量的ESAs。其次,目前尚无经过充分验证的、可商购的抗体用于在蛋白质水平鉴定细胞内或细胞表面Epo - R的存在及其功能。因此,对于之前仅使用抗体检测Epo - R的研究数据,必须谨慎解读。鉴于文献中的结果存在分歧,这些方法学上的局限性表明,临床前研究的结果在与癌症患者的临床相关性方面绝不能过度解读。

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