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New insights into erythropoietin and epoetin alfa: mechanisms of action, target tissues, and clinical applications.

机译:促红细胞生成素和促红细胞生成素α的新见解:作用机理,靶组织和临床应用。

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摘要

Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the treatment of various anemias. The mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in cancer patients are reviewed here. Epoetin alfa may also attenuate the cognitive dysfunction associated with cancer therapy. Interestingly, functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues. Of particular importance, epoetin alfa confers neurotrophic and neuroprotective effects in cultured neurons and in several animal models for neurologic disease. In one clinical trial, epoetin alfa appeared to limit functional and histologic damage in patients with stroke. Therefore, in cancer patients receiving chemotherapy, the beneficial effects of epoetin alfa could be mediated not only through enhanced erythrocyte production but also via direct effects on the nervoussystem. Further investigation into the nonerythropoietic effects of epoetin alfa could broaden its clinical utility for patients with cancer and also provide new therapies for various neurologic disorders.
机译:重组人促红细胞生成素(epoetin alfa)已被证明可治疗多种贫血。本文综述了内源性促红细胞生成素的作用机制和促红细胞生成素α在刺激癌症患者红细胞产生和改善生活质量方面的治疗用途。依泊汀α也可以减轻与癌症治疗有关的认知功能障碍。有趣的是,功能性内源性促红细胞生成素受体信号通路已在许多非促红细胞组织中得到证实。尤为重要的是,依泊汀α在培养的神经元和几种神经系统疾病的动物模型中具有神经营养和神经保护作用。在一项临床试验中,依泊汀α似乎可以限制中风患者的功能和组织学损害。因此,在接受化疗的癌症患者中,依泊汀α的有益作用不仅可以通过增加红血球的产生来介导,还可以通过对神经系统的直接作用来介导。对依泊汀α的非促红细胞作用的进一步研究可以扩大其对癌症患者的临床应用,也可以为各种神经系统疾病提供新的疗法。

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