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昂科纳酶:一种具有抗肿瘤活性的核糖核酸酶

[Onconase: a ribonuclease with antitumor activity].

作者信息

Zwolińska Małgorzata, Smolewski Piotr

机构信息

Klinika Hematologii Uniwersytetu Medycznego w Łodzi, Łódź.

出版信息

Postepy Hig Med Dosw (Online). 2010 Feb 19;64:58-66.

Abstract

Onconase (ranpirnase) is a homologous protein obtained from Rana pipiens frog eggs. The activity of onconase, and particularly its antitumor effect, is strictly connected with ribonuclease(RN-ase) activity. Onconase induces cell death through the decomposition of inner cellular RNA,inhibition of protein synthesis, and inhibition of cell growth and proliferation and it also specifically triggers tumor cell apoptosis. A very important mechanisms of its cytotoxicity is also its antioxidant activity. The results of preclinical trials demonstrated a high activity of onconase against tumor cells, also those resistant to cytostatics. Moreover, onconase showed synergic activity with other commonly used anticancer drugs. Several clinical trials were performed on patients suffering from kidney, breast, and pancreatic cancers. Most recently a phase III study of onconase in patients with mesothelioma was completed. There are also ongoing phase I and II clinical trials with non-small-cell lung cancer (NSCLC).

摘要

昂科纳酶(兰瑞肽酶)是一种从豹蛙蛙卵中获得的同源蛋白。昂科纳酶的活性,尤其是其抗肿瘤作用,与核糖核酸酶(RN酶)活性密切相关。昂科纳酶通过分解细胞内RNA、抑制蛋白质合成以及抑制细胞生长和增殖来诱导细胞死亡,并且还能特异性地触发肿瘤细胞凋亡。其细胞毒性的一个非常重要的机制也是其抗氧化活性。临床前试验结果表明昂科纳酶对肿瘤细胞具有高活性,对细胞抑制剂耐药的肿瘤细胞也有活性。此外,昂科纳酶与其他常用抗癌药物表现出协同活性。对患有肾癌、乳腺癌和胰腺癌的患者进行了多项临床试验。最近,一项关于昂科纳酶治疗间皮瘤患者的III期研究已经完成。针对非小细胞肺癌(NSCLC)的I期和II期临床试验也在进行中。

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