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EDIM-TKTL1/Apo10血液检测:一种基于先天免疫系统的液体活检技术,用于癌症的早期检测、特征分析和靶向治疗。

EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the Early Detection, Characterization and Targeted Treatment of Cancer.

作者信息

Coy Johannes F

机构信息

Zyagnum AG, Lyoner Straße 20, D-60528 Frankfurt am Main, Germany.

出版信息

Int J Mol Sci. 2017 Apr 20;18(4):878. doi: 10.3390/ijms18040878.

Abstract

Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the innate immune system. Activated monocytes (macrophages) phagocytose unwanted cells/cell fragments from the whole body including solid tissues. As they return to the blood, macrophages can be used for a non-invasive detection of biomarkers, thereby providing high sensitivity and specificity, because the intracellular presence of biomarkers is due to an innate immune response. Flow cytometry analysis of blood enables the detection of macrophages and phagocytosed intracellular biomarkers. In order to establish a pan-cancer test, biomarkers for two fundamental biophysical mechanisms have been exploited. The DNaseX/Apo10 protein epitope is a characteristic of tumor cells with abnormal apoptosis and proliferation. Transketolase-like 1 (TKTL1) is a marker for an anaerobic glucose metabolism (Warburg effect), which is concomitant with invasive growth/metastasis and resistant to radical and apoptosis inducing therapies. The detection of Apo10 and TKTL1 in blood macrophages allowed a sensitive (95.8%) and specific (97.3%) detection of prostate, breast and oral squamous cell carcinomas. Since TKTL1 represents a drugable target, the EDIM based detection of TKTL1 enables a targeted cancer therapy using the vitamin derivatives oxythiamine or benfo-oxythiamine.

摘要

单核细胞表位检测(EDIM)是一种利用先天免疫系统的液体活检方法。活化的单核细胞(巨噬细胞)会吞噬来自全身包括实体组织的不需要的细胞/细胞碎片。当它们回到血液中时,巨噬细胞可用于生物标志物的非侵入性检测,从而提供高灵敏度和特异性,因为生物标志物在细胞内的存在是由于先天免疫反应。血液的流式细胞术分析能够检测巨噬细胞和吞噬的细胞内生物标志物。为了建立一种泛癌检测方法,已利用了两种基本生物物理机制的生物标志物。DNaseX/Apo10蛋白表位是具有异常凋亡和增殖的肿瘤细胞的特征。转酮醇酶样1(TKTL1)是无氧糖代谢(瓦伯格效应)的标志物,这与侵袭性生长/转移相关,并且对自由基和诱导凋亡的疗法具有抗性。在血液巨噬细胞中检测Apo10和TKTL1能够对前列腺癌、乳腺癌和口腔鳞状细胞癌进行灵敏(95.8%)且特异(97.3%)的检测。由于TKTL1代表一个可成药靶点,基于EDIM对TKTL1的检测能够使用维生素衍生物氧硫胺或苯甲酰氧硫胺进行靶向癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bc/5412459/605c6989b6bc/ijms-18-00878-g001.jpg

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