Photodynamic diagnosis of malignant brain tumor: analysis of molecular mechanisms and application to clinical diagnosis

最近已经开发了放射性引导的大体全切除术，其中施用5-氨基乙酰丙酸（ALA）作为原卟啉IX（PpIX）的前体。本研究旨在深入了解ALA诱导PpIX在恶性脑肿瘤中蓄积的分子机制。通过比较基因表达谱，发现PpIX在脑肿瘤中的积累受两种转运蛋白PEPT和ABCG 2的调节，这两种转运蛋白分别转运ALA和PpIX。转录因子Nrf 2在调节ABCG 2基因表达中起重要作用，其中Nrf 2基因中的一个SNP（-617C>A）被认为是关键参与者。因此，我们开发了一种快速简便的方法来检测SNP等位基因。此外，我们确定了一种有效抑制ABCG 2的药物，并可能显着提高基于ALA的光动力学诊断和治疗的疗效。

Fluorescence-guided gross-total resection has recently been developed, where 5-aminolevulinic acid (ALA) is administered as the precursor of protoporphyrin IX (PpIX). This study has been undertaken to gain insight into the molecular mechanism underlying ALA-induced PpIX accumulation in malignant brain tumors. By comparing gene expression profiles, PpIX accumulation in brain tumor was found to be regulated by two transporters PEPT and ABCG2 that transport ALA and PpIX, respectively. Transcription factor Nrf2 plays a significant role in regulating ABCG2 gene expression, where one SNP (-617C>A) in the Nrf2 gene is suggested to be critically involved. We therefore developed a rapid and simple method to detect that SNP allele. Furthermore, we identified one drug that is potent for ABCG2-inhibition and may significantly enhance the efficacy of ALA-based photodynamic diagnosis and therapy.