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快速类固醇作用的转化研究。

Translational research on rapid steroid actions.

机构信息

Clinical Pharmacology Mannheim, University of Heidelberg, Mannheim, Germany.

出版信息

Steroids. 2010 Aug-Sep;75(8-9):619-23. doi: 10.1016/j.steroids.2009.09.007. Epub 2009 Sep 24.

Abstract

Translational research is a burgeoning science that shows potential to improve the transition of research from bench to bedside. This novel science explores all major aspects of preclinical and clinical issues which are relevant for the success of translational pharmaceutical or medical device/diagnostic innovations. This includes target risk assessment, biomarker evaluation and predictivity grading both for efficacy and toxicity, early human trial design adequate to guide stop/go decisions on grounds of biomarker panels, and biostatistical methods to analyze multiple readout situations and quantify risk projections. Representing a comparably novel science, rapid steroid actions have been recognized to carry potential clinical implications in various fields. Findings in this field have not yet been successfully translated into clinically relevant new medicines except for neurosteroids. A promising compound is the membrane estrogen receptor agonist STX, which may be applicable for estrogen withdrawal symptoms. Nongenomic vitamin D analogs may be useful as antiinflammatory, anticancer or diabetes preventing agents. Further the membrane thyroid receptor agonist tetrac may be useful in cancer treatment. Unfortunately lazaroids (membrane-only active glucocorticoids), which have been clinically tested as neuroprotective agents, had to be abandoned because of lacking clinical efficacy. Yet, the hierarchy of antirheumatic glucocorticoid action in regard to their clinical potency may better correlate with their membrane effects than their ability to bind to the classic glucocorticoid receptor. To improve the translational success of the rapid actions of steroids research, scientists should become familiar with major aspects of translational work and always seek for translational dimensions in their research.

摘要

转化研究是一门新兴的科学,具有改善研究从实验室到临床转化的潜力。这门新科学探索了与转化制药或医疗设备/诊断创新成功相关的所有主要临床前和临床问题。这包括目标风险评估、生物标志物评估和预测性分级,既适用于疗效也适用于毒性,早期人体试验设计充分,可根据生物标志物组指导停止/继续决策,以及生物统计学方法分析多种读出情况并量化风险预测。快速类固醇作用代表了一个相对较新的科学领域,已经被认为在各个领域具有潜在的临床意义。除了神经甾体外,这一领域的发现尚未成功转化为具有临床相关性的新药。一种有前途的化合物是膜雌激素受体激动剂 STX,它可能适用于雌激素撤退症状。非基因组维生素 D 类似物可能作为抗炎、抗癌或预防糖尿病的药物有用。此外,膜甲状腺受体激动剂 tetrac 可能对癌症治疗有用。不幸的是,拉扎罗伊德(仅具有膜活性的糖皮质激素)已被临床测试为神经保护剂,但由于缺乏临床疗效而不得不放弃。然而,抗风湿糖皮质激素作用的临床效力等级与其膜作用相关性可能优于与经典糖皮质激素受体的结合能力。为了提高类固醇快速作用转化研究的成功率,科学家们应该熟悉转化工作的主要方面,并在研究中始终寻求转化维度。

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