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A report on the use of animal models and phenotyping methods in pulmonary hypertension research

机译:动物模型和表型方法在肺动脉高压研究中的应用报告

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摘要

The failure to translate positive results from preclinical studies into new clinical therapies is a major problem throughout medical research. Specifically, in pulmonary hypertension, numerous research studies have shown beneficial effects of new therapies in experimental models, but these have largely failed to translate into clinical benefit in human trials. This is undoubtedly due, at least in part, to inadequacies of the models, but while monogenic animal models will never fully recapitulate human disease, they do still provide the best platform on which to test novel therapeutic agents. In the postgenomic era, there is emphasis on a greater understanding of disease pathogenesis, which has subsequently led to the development of both new targets and new models in which to test them. The evolution of new technologies means that we are now better equipped to phenotype these models, but the level of detail provided varies dramatically throughout the literature. However, subtle variances in experimental methods can make comparing data/findings between research laboratories difficult and are a possible contributing factor to variance between preclinical and clinical data. The aim of this report was to capture information on current practice for use of the growing array of animal models, to help movement toward developing guidelines and standards for the “best” use of animal models of pulmonary hypertension.
机译:未能将临床前研究的阳性结果转化为新的临床疗法是整个医学研究的主要问题。具体而言,在肺动脉高压中,许多研究表明新疗法在实验模型中具有有益效果,但在人体试验中,这些疗法很大程度上未能转化为临床益处。毫无疑问,这至少部分是由于模型的不足所致,但是尽管单基因动物模型将永远无法完全概括人类疾病,但它们仍然提供了测试新型治疗剂的最佳平台。在后基因组时代,人们对​​疾病的发病机理有了更深入的了解,从而导致了新靶标和新模型的开发。新技术的发展意味着我们现在已经能够更好地对这些模型进行表型化,但是所提供的详细程度在整个文献中差异很大。但是,实验方法中的细微差异可能会导致难以比较研究实验室之间的数据/发现,并且可能是导致临床前数据与临床数据之间差异的一个可能因素。本报告的目的是收集有关使用越来越多的动物模型的当前实践信息,以帮助朝着“最佳”使用肺动脉高压动物模型的指导方针和标准发展。

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