权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The secret of radiation-surviving cell : multidisciplinary approach to eradicate cancer

辐射存活细胞的秘密：根除癌症的多学科方法

基本信息

批准号：
20390319
负责人：
NISHIOKA Takeshi
金额：
$ 10.98万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390319/
关键词：
放射線生物学 irradiation p16 repopulation mitosis MMP HIF1-alpha radiation cancer stem cell cell movement Radiotherapy TGFB-1 細胞形態細胞運動

项目摘要

Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated ; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated ; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.

用任何细胞毒性药物治疗都可以触发肿瘤中存活的细胞比以前更快地分裂。这一现象被广泛认为是“人口再增长”。为了更好地阐明机制，进行了基因表达谱分析和病理学实验。使用小鼠纤维肉瘤细胞系QRsP。用10戈伊照射细胞。进行集落测定和克隆。建立了6个克隆。对在第2次10戈伊照射时显示最大菌落数的克隆进行cDNA分析。然后进行小鼠移植实验。cDNA分析表明，细胞周期蛋白依赖性激酶抑制剂，p16和p57下调，14.8和12.0倍，分别为耐受克隆。基质金属蛋白酶3和13分别上调22.5和25.8倍。抗性无性系的移植率为100%（5/5），而亲本的移植率为40%（2/5）。在光学显微镜下，亲本的平均有丝分裂细胞数为4.0+/-3.9，耐受克隆的平均有丝分裂细胞数为12.8+/-3.4（p<0.01，Student’s t检验）。这项研究表明，再增殖不是一个暂时的反应，照射。它可能是由“克隆”基因表达变化引起的，尽管目前尚不清楚这些变化是归因于耐受细胞选择还是归因于基因突变/修饰。