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肝细胞癌中α-甲胎蛋白靶向报告基因表达成像

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

作者信息

Kim Kwang Il, Chung Hye Kyung, Park Ju Hui, Lee Yong Jin, Kang Joo Hyun

机构信息

Kwang Il Kim, Ju Hui Park, Yong Jin Lee, Joo Hyun Kang, Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, South Korea.

出版信息

World J Gastroenterol. 2016 Jul 21;22(27):6127-34. doi: 10.3748/wjg.v22.i27.6127.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

摘要

肝细胞癌(HCC)是东亚地区最常见的癌症之一,且其全球发病率正在上升。人们已开发出众多实验模型,以加深我们对HCC致病机制的理解,并评估新的治疗方法。分子成像是一种便捷且最新的生物医学工具,能够在活体中对生物过程进行可视化、特征化和定量分析。特别是基于报告基因表达的分子成像,可通过获取由肿瘤特异性增强子/启动子驱动的报告基因表达图像,来阐明肿瘤特异性事件或过程。在本综述中,我们讨论了各种实验性HCC小鼠模型的优缺点,并展示了在HCC小鼠模型中由甲胎蛋白(AFP)增强子/启动子系统驱动的肿瘤特异性报告基因表达的体内图像。当前的HCC发生小鼠模型是通过异种移植、致癌物诱导和基因工程建立的,代表了肿瘤诱导因子和肿瘤位置的范围。针对这些不同的HCC小鼠模型,介绍了由AFP增强子/启动子驱动的报告基因的成像分析方法。这种分子成像可提供有关致癌作用和肿瘤进展的纵向信息。我们期望AFP靶向报告基因表达成像系统的临床应用将有助于检测表达AFP的HCC肿瘤,并筛查因疾病或药物治疗导致的AFP水平升高/降低情况。

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