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[小儿L-天冬酰胺酶治疗的最新进展]

[Update on L-asparaginase treatment in paediatrics].

作者信息

Moscardó Guilleme C, Fernández Delgado R, Sevilla Navarro J, Astigarraga Aguirre I, Rives Solà S, Sánchez de Toledo Codina J, Fuster Soler J L, Parra Ramirez L, Molina Garicaño J, González Martínez B, Madero López L

机构信息

Hospital General Universitario, Alicante, España.

出版信息

An Pediatr (Barc). 2013 Nov;79(5):329.e1-329.e11. doi: 10.1016/j.anpedi.2013.03.015. Epub 2013 May 31.

Abstract

L-asparaginase (L-ASP) is one of the cornerstones of the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma. It is an enzyme of bacterial origin capable of transforming L-asparagine to aspartic acid. The extracellular depletion of L-asparagine inhibits protein synthesis in lymphoblasts, inducing their apoptosis. Numerous studies have demonstrated that treatment with L-ASP improves survival of patients, but there are clear differences in the characteristics of the three currently available formulations. This article reviews the dosage, activity and side effects of the two L-ASP derived from Escherichia coli (native and pegylated), and the one derived from Erwinia chrysanthemi (Erwinia ASP). Despite its indisputable indication over the past50 years, there are still many points of contention, and its use is still marked by the side effects of the inhibition of protein synthesis. The short half-life of native forms, and the most frequently used parenteral administration by intramuscular injections, affects the quality of life of the patients. Therefore, recent studies claim to evaluate alternatives, such as the formulation of longer half-life pegylated L-ASP, and the use of intravenous formulations. There are encouraging results to date with both preparations. Still, further studies are needed to establish which should be the formulation and frontline indicated route of administration, optimal dosing, and management of adverse effects.

摘要

L-天冬酰胺酶(L-ASP)是急性淋巴细胞白血病和非霍奇金淋巴瘤治疗的基石之一。它是一种源自细菌的酶,能够将L-天冬酰胺转化为天冬氨酸。L-天冬酰胺的细胞外消耗会抑制淋巴母细胞中的蛋白质合成,诱导其凋亡。大量研究表明,L-ASP治疗可提高患者生存率,但目前可用的三种制剂在特性上存在明显差异。本文综述了两种源自大肠杆菌的L-ASP(天然型和聚乙二醇化型)以及源自菊欧文氏菌的L-ASP(菊欧文氏菌ASP)的剂量、活性和副作用。尽管在过去50年中其适应证无可争议,但仍存在许多争议点,其使用仍以蛋白质合成抑制的副作用为特征。天然形式的半衰期短,且最常用的肌内注射肠胃外给药方式影响患者的生活质量。因此,最近的研究声称要评估替代方案,如半衰期更长的聚乙二醇化L-ASP制剂以及静脉制剂的使用。迄今为止,这两种制剂都有令人鼓舞的结果。不过,仍需要进一步研究来确定哪种制剂、一线给药途径、最佳剂量以及不良反应的管理方式。

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