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碱性磷酸酶:一种新型荧光探针,作为一种潜在的即时诊断工具用于评估脑膜瘤复发风险。

AlkaPhos: a novel fluorescent probe as a potential point-of-care diagnostic tool to estimate recurrence risk of meningiomas.

作者信息

Hemmer Sina, Hui Xin, Draeger Julia, Menges Johannes, Schwarz Eva C, Wrede Arne, Oertel Joachim, Kaestner Lars, Jung Gregor, Urbschat Steffi

机构信息

Department of Neurosurgery, Saarland University Medical Center, Homburg, Germany.

Biophysical Chemistry, Saarland University, Saarbrücken, Germany.

出版信息

Neurosurg Rev. 2025 Jan 8;48(1):27. doi: 10.1007/s10143-024-03172-8.

DOI:10.1007/s10143-024-03172-8
PMID:39775316
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11706915/
Abstract

Deletion of the short arm of chromosome 1 (1p) increases recurrence rates in meningiomas by up to 33%, regardless of tumor grade, correlating with absence of intracellular alkaline phosphatase enzyme activity. Current screening methods for 1p deletion like fluorescence in situ hybridization (FISH) and loss of heterozygosity (LOH) analysis are resource-intensive. This study evaluated AlkaPhos, a novel fluorescent probe, for detecting alkaline phosphatase in meningioma cells and compared findings with FISH, LOH, and histochemical analysis. AlkaPhos sensitivity in detecting alkaline phosphatase on BEN-MEN-1 cells and primary meningioma cultures was assessed via microscopic fluorescent ratio measurements. FISH and LOH were conducted on the same tumors to detect 1p deletions. Histochemical analysis served as a reference. AlkaPhos results were compared with FISH, LOH, and histochemical analysis. AlkaPhos effectively indicated alkaline phosphatase activity in BEN-MEN-1 cells and correctly identified 1p deletion in 8/14 primary meningioma cultures, matching FISH and LOH findings, respectively. AlkaPhos showed potential superiority over histochemical analysis in identifying tumors with 1p deletion and LOH of 1p. AlkaPhos bears potential as a future diagnostic tool for identifying alkaline phosphatase absence in meningiomas, indicative of 1p deletion. Further evaluation on a larger sample size is necessary for routine clinical application.

摘要

1号染色体短臂(1p)的缺失会使脑膜瘤的复发率提高33%,无论肿瘤分级如何,这与细胞内碱性磷酸酶活性缺失相关。目前用于检测1p缺失的筛查方法,如荧光原位杂交(FISH)和杂合性缺失(LOH)分析,资源消耗大。本研究评估了一种新型荧光探针AlkaPhos,用于检测脑膜瘤细胞中的碱性磷酸酶,并将结果与FISH、LOH和组织化学分析进行比较。通过显微镜荧光比率测量评估AlkaPhos在检测BEN-MEN-1细胞和原发性脑膜瘤培养物中碱性磷酸酶的敏感性。对同一肿瘤进行FISH和LOH检测以检测1p缺失。组织化学分析作为参考。将AlkaPhos的结果与FISH、LOH和组织化学分析进行比较。AlkaPhos有效地显示了BEN-MEN-1细胞中的碱性磷酸酶活性,并在14例原发性脑膜瘤培养物中的8例中正确识别出1p缺失,分别与FISH和LOH结果相符。在识别有1p缺失和1p LOH的肿瘤方面,AlkaPhos显示出优于组织化学分析的潜在优势。AlkaPhos有潜力成为未来诊断脑膜瘤中碱性磷酸酶缺失(提示1p缺失)的诊断工具。为用于常规临床应用,有必要对更大样本量进行进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e4/11706915/5496f35a2503/10143_2024_3172_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e4/11706915/5496f35a2503/10143_2024_3172_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e4/11706915/677525915f4f/10143_2024_3172_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e4/11706915/3ad67ee86780/10143_2024_3172_Fig2_HTML.jpg
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