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去铁胺铁螯合作用增加异种移植脑肿瘤模型中 δ-氨基酮戊酸诱导的原卟啉 IX。

Deferoxamine iron chelation increases delta-aminolevulinic acid induced protoporphyrin IX in xenograft glioma model.

机构信息

Dartmouth Medical School, Dartmouth College, Hanover, NH, USA.

出版信息

Photochem Photobiol. 2010 Mar-Apr;86(2):471-5. doi: 10.1111/j.1751-1097.2009.00664.x. Epub 2009 Dec 7.

DOI:10.1111/j.1751-1097.2009.00664.x
PMID:20003159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2875336/
Abstract

Exogenous administration of delta-aminolevulinic acid (delta-ALA) leads to selective accumulation of protoporphyrin IX (PpIX) in brain tumors, and has shown promising results in increasing extent of resection in fluorescence-guided resection (FGR) of brain tumors. However, this approach still suffers from heterogeneous staining and so some tumor margins may go undetected because of this variation in PpIX production. The aim of this study was to test the hypothesis that iron chelation therapy could increase the level of fluorescence in malignant glioma tumors. Mice implanted with xenograft U251-GFP glioma tumor cells were given a 200 mg kg(-1) dose of deferoxamine (DFO), once a day for 3 days prior to delta-ALA administration. The PpIX fluorescence observed in the tumor regions was 1.9 times the background in animal group without DFO, and 2.9 times the background on average, in the DFO pre-treated group. A 50% increase in PpIX fluorescence contrast in the DFO group was observed relative to the control group (t-test P-value = 0.0020). These results indicate that iron chelation therapy could significantly increase delta-ALA-induced PpIX fluorescence in malignant gliomas, pointing to a potential role of iron chelation therapy for more effective FGR of brain tumors.

摘要

外源性给予 δ-氨基酮戊酸(δ-ALA)会导致原卟啉 IX(PpIX)在脑肿瘤中的选择性积累,并已显示出在荧光引导切除(FGR)脑肿瘤中增加切除范围的有前景的结果。然而,这种方法仍然存在染色不均匀的问题,因此由于 PpIX 产生的这种变化,一些肿瘤边缘可能无法被检测到。本研究旨在测试铁螯合疗法是否可以增加恶性胶质瘤肿瘤荧光水平的假设。在给予 δ-ALA 之前,将植入异种移植 U251-GFP 神经胶质瘤肿瘤细胞的小鼠每天给予 200mg/kg 的去铁胺(DFO),连续 3 天。在没有 DFO 的动物组中,肿瘤区域观察到的 PpIX 荧光是背景的 1.9 倍,而在 DFO 预处理组中平均为背景的 2.9 倍。与对照组相比,DFO 组的 PpIX 荧光对比度增加了 50%(t 检验 P 值=0.0020)。这些结果表明,铁螯合疗法可显著增加恶性胶质瘤中 δ-ALA 诱导的 PpIX 荧光,表明铁螯合疗法在更有效地进行 FGR 脑肿瘤方面具有潜在作用。

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