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比较肿瘤基因组和组织学相关性与影像学变化:一项小鼠SCC VII模型研究。

Comparing genomic and histologic correlations to radiographic changes in tumors: a murine SCC VII model study.

作者信息

Yang Yi-Shan, Guccione Samira, Bednarski Mark D

机构信息

Lucas MRS Research Center, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

Acad Radiol. 2003 Oct;10(10):1165-75. doi: 10.1016/s1076-6332(03)00327-1.

DOI:10.1016/s1076-6332(03)00327-1
PMID:14587635
Abstract

RATIONALE AND OBJECTIVES

To investigate the correlation between the temporal changes in T1- and T2-weighted contrast-enhanced magnetic resonance imaging (MRI), histologic evaluation, and genomic analysis using oligonucleotide microarrays in a murine squamous cell carcinoma tumor models.

MATERIALS AND METHODS

The squamous cell carcinoma (SCC VII) cell line was used to initiate subcutaneous tumors in mice. This mouse model has been used as a model for human head and neck carcinomas. Animals were imaged using contrast enhanced MRI (CE-MRI). Different stages of tumor growth were defined based on changes in the T1- and T2-weighted MRI patterns. The contrast enhancing (CE) and nonenhancing (NE) regions of the tumors were marked and biopsied for oligonucleotide microarray and histologic analysis. Tumors with no differential contrast enhancement were used as controls.

RESULTS

Distinct temporal stages of tumor progression can be defined using both T1- and T2-weighted CE-MRI and microarray analysis. The early stage tumors show a homogeneous contrast enhancement pattern in the T1- and T2-weighted images with no significant differential gene expression from the center and periphery of the tumor. The more advanced tumors that show discrete regions of contrast enhancement in the post-contrast T1-weighted MRIs and tissues from the CE and NE regions show distinctly differential gene expression profiles. Histologic analysis (hematoxylin-eosin stain) showed that the samples obtained from the periphery and center of the early stage tumors and the CE and NE regions from these more advanced tumors were similar. The gene expression profiles of late-stage tumors that showed changes in T2-weighted MRI signal intensity were consistent with tissue degradation in the NE region, which also showed characteristic signs of tissue necrosis in histologic analysis.

CONCLUSION

These results show that temporal changes in T1- and T2-weighted CE-MRI are related to distinct gene expression profiles, and histologic analysis may not be sufficient to detect these detailed changes. As tumors progress, discrete regions of post-contrast T1 enhancement are identified; these regions have distinct gene expression patterns despite similar histologic features. In late-stage tumors, regions of T2 signal changes are observed which correspond with tissue necrosis.

摘要

原理与目的

在小鼠鳞状细胞癌肿瘤模型中,研究T1加权和T2加权对比增强磁共振成像(MRI)的时间变化、组织学评估以及使用寡核苷酸微阵列进行基因组分析之间的相关性。

材料与方法

使用鳞状细胞癌(SCC VII)细胞系在小鼠体内引发皮下肿瘤。该小鼠模型已被用作人类头颈癌的模型。使用对比增强MRI(CE-MRI)对动物进行成像。根据T1加权和T2加权MRI模式的变化定义肿瘤生长的不同阶段。标记肿瘤的对比增强(CE)和非增强(NE)区域,并进行活检以进行寡核苷酸微阵列和组织学分析。无差异对比增强的肿瘤用作对照。

结果

使用T1加权和T2加权CE-MRI以及微阵列分析可以定义肿瘤进展的不同时间阶段。早期肿瘤在T1加权和T2加权图像中显示均匀的对比增强模式,肿瘤中心和周边的基因表达无明显差异。在对比后T1加权MRI中显示离散对比增强区域的更晚期肿瘤以及来自CE和NE区域的组织显示出明显不同的基因表达谱。组织学分析(苏木精-伊红染色)表明,从早期肿瘤的周边和中心以及这些更晚期肿瘤的CE和NE区域获得的样本相似。T2加权MRI信号强度发生变化的晚期肿瘤的基因表达谱与NE区域的组织降解一致,在组织学分析中也显示出组织坏死的特征性迹象。

结论

这些结果表明,T1加权和T2加权CE-MRI的时间变化与不同的基因表达谱相关,组织学分析可能不足以检测这些详细变化。随着肿瘤进展,可识别出对比后T1增强的离散区域;尽管组织学特征相似,但这些区域具有不同的基因表达模式。在晚期肿瘤中,观察到T2信号变化区域,其与组织坏死相对应。

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