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基于微小RNA的选定胃肠道癌症动物模型治疗

MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers.

作者信息

Merhautova Jana, Demlova Regina, Slaby Ondrej

机构信息

Molecular Oncology II - Solid Cancer, Central European Institute of Technology, Masaryk UniversityBrno, Czech Republic; Department of Pharmacology, Faculty of Medicine, Masaryk UniversityBrno, Czech Republic.

Department of Pharmacology, Faculty of Medicine, Masaryk University Brno, Czech Republic.

出版信息

Front Pharmacol. 2016 Sep 27;7:329. doi: 10.3389/fphar.2016.00329. eCollection 2016.

Abstract

Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of and evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs) is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method), pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration) and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.

摘要

胃肠道癌是全球20种最常见的癌症疾病之一,人们一直迫切希望将具有新作用机制的新疗法应用于临床实践。大量证据表明,病理失衡的微小RNA(miRNA)的外源变化能够改变癌细胞表型。本综述分析了在胃癌、胰腺癌、胆囊癌和结直肠癌动物模型中基于miRNA的临床前治疗尝试。从400多篇原始文章中,发现有26篇评估了局部或全身施用的miRNA模拟物、前体、表达载体或抑制剂的效果,这是一种具有较高转化潜力的方法。我们专注于梳理有关所用动物模型(动物品系、细胞系、异种移植方法)、药理学方面(寡核苷酸化学、递送系统、剂量、给药途径)和毒理学评估的现有信息。我们还总结了基于miRNA疗法的药代动力学和毒性领域的研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41b/5037200/d0f317b8f287/fphar-07-00329-g0001.jpg

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