食管癌放疗过程中肿瘤干细胞加速再增殖与乏氧微环境关系及PET分子影像研究

项目名称： 食管癌放疗过程中肿瘤干细胞加速再增殖与乏氧微环境关系及PET分子影像研究

项目编号： No.81472813

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 岳金波

作者单位： 山东省医学科学院

项目金额： 72万元

中文摘要： 放疗是食管癌的主要治疗手段，但疗效仍不令人满意。肿瘤加速再增殖是导致放疗耐受的重要生物学因素，其本质是放疗过程中聚集在乏氧微环境下的肿瘤干细胞发生了氧合、加速增殖。我们前期研究发现，PET分子影像是监测肿瘤加速再增殖及乏氧的理想手段，于是推测可以利用PET分子影像结合肿瘤干细胞标志物检测肿瘤干细胞动态变化。本项目拟通过动物实验和临床研究，（1）与病理标本比对，确定PET分子影像反映的加速再增殖与乏氧微环境之间的关系（2）以肿瘤干细胞生物荧光成像和免疫组化比对，确定PET分子影像能否监测肿瘤干细胞加速再增殖（3）比较PET分子影像检测的肿瘤干细胞乏氧微环境和加速再增殖生物学壁龛与放疗耐受的关系，探讨应用PET分子影像构建肿瘤干细胞生物学靶区的可能性。本研究将揭示食管癌放疗耐受与肿瘤干细胞加速再增殖、乏氧微环境之间的关系，并为动态监测肿瘤干细胞变化和构建肿瘤干细胞生物学靶区提供分子影像手段。

中文关键词： C06_食管肿瘤；加速再增殖；乏氧微环境；肿瘤干细胞；放射治疗

英文摘要： Radiotherapy is main modality for esophageal cancer, but the outcome remains unsatisfying. Accelerated repopulation of tumor cells during radiotherapy is believed to contribute to radioresistance and is an important cause for treatment failure. In essence the mechanism of tumor accelerated repopulation involves the accelerated proliferation of clonogenic cancer stem cells (CSCs). Our studies found that PET molecular imaging could detect tumor accelerated repopulation and hypoxia during radiotherapy in esophageal cancer. It is hypothesized that detecting CSCs changing during treatment by PET molecular imaging together with molecular stem cell markers will be helpful to reveal biological mechanism of radio-resistance and further guide individualized radiotherapy. This study using tumor model and clinical data is proposed to: (1) define the relationship between accelerated repopulation and hypoxia microenvironment measured by PET molecular imaging based on pathology; (2) identify whether PET molecular imaging could detect accelerated repopulation of CSCs during radiotherapy compared with fluorescence-based optical imaging and immunohistochemistry imaging; (3) analyze the relationship between radio-resistance and biological niches including accelerated repopulation and hypoxia detected by PET molecular imaging; explore the potential role of PET molecular imaging in defining CSCs biological target. This study will reveal the biological niches including accelerated repopulation and hypoxia correlated with radio-resistance and provide a molecular imaging tool for detecting CSCs dynamically and defining biological target of CSCs during radiotherapy in esophageal cancer.

英文关键词： esophageal cancer;accelerated repopulation;hypoxia microenvironment;cancer stem cells;radiotherapy