基于临床手术标本的胰腺癌原位移植模型建立及评价
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(1. 沈阳军区总医院医务部,沈阳 110015; 2. 第四军医大学实验动物中心,西安 710032)

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国家自然科学基金(No. 31572340,No. 31772546),军队实验动物专项课题(No. SYDW2016?006)


Establishment and characterization of a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer
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(1. Department of Medical Administration, the General Hospital of Shenyang Military Region, Shenyang 110015, China. 2. Laboratory Animal Center, the Fourth Military Force Medical University, Xi’an 710032)

Fund Project:

National Natural Science Foundation of China (No. 315723240, No. 31772546), Supported by Laboratory Animal Foundation of Military(No. SYDW2016?006)

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    摘要:

    目的 建立基于临床肿瘤标本的胰腺癌原位移植模型,开展模型的评价研究?方法 将临床新鲜的胰腺癌手术标本移植到裸鼠胰腺部位,建立原位异种移植模型(PDOX),通过活体成像技术和PET/ CT 对肿瘤生长状况进行评价;采用STR 技术分析移植瘤的来源,通过组织形态观察和免疫组化判定移植瘤的病理学特征,同时检测PDOX 模型外周血中CA19?9 的表达水平?结果 模型建立6 周后,通过活体成像观察到近红外荧光信号明显富集在肿瘤部位,通过荧光强度可以初步判断肿瘤位置和大小;使用小动物PET/ CT 可清晰观察到腹部18 F?FDG分子探针富集区域,与预期的肿瘤位置和大小一致;安死术后,解剖分离的各个脏器组织及肿瘤组织,通过近红外荧光成像进一步确认肿瘤生长状况;STR 检测证实移植瘤人源性比率为99.99%;组织形态学和免疫组化分析表明移植肿瘤生长于裸鼠胰腺;血清中CA19?9 检测进一步证实了胰腺癌的发生?结论 成功建立了人胰腺癌原位异种移植模型,通过小动物活体成像?PET/ CT 等技术对模型进行了全面评估,为胰腺癌的发病机制和治疗研究提供了良好的动物模型?

    Abstract:

    Objective To establish and evaluate a patient?derived orthotopic xenograft ( PDOX) model of pancreatic cancer. Methods Tissues of patient?derived pancreatic tumor were transplanted into nude mouse pancreas by surgery. The PDOX models were evaluated by the small animal near infrared fluorescence (NIRF) optical imaging and PET/ CT. The traceability of PDOX models was detected by STR technology, and the pathological changes were observed by H&E staining, immunohistochemistry, and serum level of CA19?9 was detected by ELISA. Results Apparent NIRF were observed to be accumulated in pancreatic site by optical imaging system. The location and size of the xenografts tumor were revealed by fluorescence intensity. The PET/ CT images with 18 F?FDG molecular probe confirmed the tumor’s location and size. Ex vivo NIRF imaging of isolated organ further showed the tumor formation. The traceability of PDOX models was 99.99% with human origin. H&E staining pathology and immunohistochemistry indicated the pancreatic cancer characteristics. The high serum level of ca19?9 confirmed the mice bearing tumor. Conclusions Pancreatic PDOX modelsare successfully established in this study, and it can be evaluated comprehensively by NIRF optical imaging and PET/ CT, providing an appropriate platform for further research of pancreatic cancer.

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张贺,张彩勤,赵勇,谭邓旭,师长宏.基于临床手术标本的胰腺癌原位移植模型建立及评价[J].中国实验动物学报,2018,26(3):296~301.

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  • 收稿日期:2018-02-27
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  • 在线发布日期: 2018-07-20
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