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丁酸及其衍生物在结直肠癌和血红蛋白病治疗中的作用。

Role of butyric acid and its derivatives in the treatment of colorectal cancer and hemoglobinopathies.

作者信息

Pouillart P R

机构信息

CAFISAP Porcine Biomedical Center, Beauvais, France.

出版信息

Life Sci. 1998;63(20):1739-60. doi: 10.1016/s0024-3205(98)00279-3.

Abstract

Butyric acid, a short chain fatty acid (SCFA), is a natural component of the animal metabolism. Physiological concentrations induce multiple and reversible biological effects. They concern regulatory mechanisms of gene expression conducing to promote markers of cell differentiation, apoptosis and cell growth control. The described hyperacetylation of histones and the induction of several immune or non-immune cell-activating mediators are consistent with the pleiotropic stimulatory effect of the agent. Butyric acid is considered as a biological response modifier (BRM) and is an interesting tool for biological studies. The history of butyric acid as a putative medication in human health is spanning since 60 years and is confusing in part because of conflicting data between exciting experimental results and clinical trials. In light of minimal impact of systemic therapy and the short half-life of the saline molecule used, it is evident that continuous infusions of butyrate are required to improve the efficacy of the treatment. Butyric acid has been viewed with skepticism because of less convenient for long-term chronic therapy. New experimental data from several studies conduced within the past decade with butyric derivatives, delivery systems, and long-acting prodrugs, have demonstrated the practical value of the therapeutic concept. To support issues regarding clinical development, it was of interest to evaluate the recent information, showing butyric acid currently considered as therapeutic purposes in the treatment of colorectal cancer and hemoglobinopathies.

摘要

丁酸是一种短链脂肪酸(SCFA),是动物新陈代谢的天然成分。生理浓度会引发多种可逆的生物学效应。这些效应涉及基因表达的调控机制,有助于促进细胞分化、凋亡和细胞生长控制的标志物。所描述的组蛋白高度乙酰化以及几种免疫或非免疫细胞激活介质的诱导与该物质的多效性刺激作用一致。丁酸被认为是一种生物反应调节剂(BRM),是生物学研究的一个有趣工具。丁酸作为一种潜在的人类健康药物的历史已有60年,部分原因是令人兴奋的实验结果和临床试验之间的数据相互矛盾,这使得情况有些混乱。鉴于全身治疗的影响最小,且所用盐分子的半衰期较短,显然需要持续输注丁酸盐以提高治疗效果。由于长期慢性治疗不太方便,丁酸一直受到怀疑。过去十年中对丁酸衍生物、递送系统和长效前药进行的几项研究得出的新实验数据,证明了这一治疗理念的实用价值。为了支持有关临床开发的问题,评估最近的信息很有意义,这些信息表明丁酸目前被认为可用于治疗结直肠癌和血红蛋白病。

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