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通过酶触发荧光探针增强γ-谷氨酰转肽酶成像,揭示放疗/化疗后混合物中的胶质瘤复发情况以实现精确病理诊断

Enhanced γ-Glutamyltranspeptidase Imaging That Unravels the Glioma Recurrence in Post-radio/Chemotherapy Mixtures for Precise Pathology via Enzyme-Triggered Fluorescent Probe.

作者信息

Shi Ben, Zhang Zhenyu, Lan Chuanjin, Wang Bao, Xu Shangchen, Ge Mingxu, Xu Ge, Zhu Tianli, Liu Yingchao, Zhao Chunchang

机构信息

Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China.

School of Medicine, Shandong University, Jinan, China.

出版信息

Front Neurosci. 2019 May 31;13:557. doi: 10.3389/fnins.2019.00557. eCollection 2019.

DOI:10.3389/fnins.2019.00557
PMID:31213974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6554337/
Abstract

Accurate pathological diagnosis of gliomas recurrence is crucial for the optimal management and prognosis prediction. The study here unravels that our newly developed γ-glutamyltranspeptidase (GGT) fluorescence probe (Figure 1A) imaging in twenty recurrent glioma tissues selectively recognizes the most malignant portion from treatment responsive tissues induced by radio/chemo-therapy (Figure 1B). The overexpression of GGT in recurrent gliomas and low level in radiation necrosis were validated by western blot analysis and immunohistochemistry. Furthermore, the ki-67 index evaluation demonstrated the significant increase of malignancy, aided by the GGT-responsive fluorescent probe to screen out the right specimen through fast enhanced imaging of enzyme activity. Importantly, our GGT-targeting probe can be used for accurate determination of pathologic evaluation of tumor malignancy, and eventually for guiding the following management in patients with recurrent gliomas.

摘要

准确的胶质瘤复发病理诊断对于优化治疗管理和预后预测至关重要。本研究揭示,我们新开发的γ-谷氨酰转肽酶(GGT)荧光探针(图1A)在20例复发性胶质瘤组织中的成像能够从放化疗诱导的治疗反应性组织中选择性识别出最具恶性的部分(图1B)。通过蛋白质免疫印迹分析和免疫组织化学验证了复发性胶质瘤中GGT的过表达以及放射性坏死中的低水平表达。此外,ki-67指数评估显示恶性程度显著增加,借助GGT反应性荧光探针通过快速增强的酶活性成像筛选出合适的标本。重要的是,我们的GGT靶向探针可用于准确确定肿瘤恶性程度的病理评估,并最终指导复发性胶质瘤患者的后续治疗管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/bbb078b7331f/fnins-13-00557-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/f7be15e8a785/fnins-13-00557-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/0127d200447c/fnins-13-00557-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/3775d7a3c8d7/fnins-13-00557-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/c2233b607c06/fnins-13-00557-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/c244f8f8a81c/fnins-13-00557-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/bbb078b7331f/fnins-13-00557-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/f7be15e8a785/fnins-13-00557-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/0127d200447c/fnins-13-00557-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/3775d7a3c8d7/fnins-13-00557-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/c2233b607c06/fnins-13-00557-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/c244f8f8a81c/fnins-13-00557-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/6554337/bbb078b7331f/fnins-13-00557-g006.jpg

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