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一种采用手术原位植入的绿色荧光蛋白标记的人结肠癌转移模型。

A GFP-labeled human colon cancer metastasis model featuring surgical orthotopic implantation.

作者信息

Chen Hong-Jin, Yang Bo-Lin, Chen Yu-Gen, Lin Qiu, Zhang Shu-Peng, Gu Yun-Fei

机构信息

Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China.

出版信息

Asian Pac J Cancer Prev. 2012;13(9):4263-6. doi: 10.7314/apjcp.2012.13.9.4263.

Abstract

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP- labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

摘要

结直肠癌已成为威胁人类健康的主要疾病。建立具有人类结直肠癌特征的动物模型,不仅有助于有效研究其发生发展机制,还能为药物筛选及疗效检测提供理想载体。在本研究中,我们通过手术原位植入(SOI)建立了一种稳定的、高表达绿色荧光蛋白(GFP)的结肠癌裸鼠自发转移模型。15只裸鼠均成功建立了SOI后转移的GFP标记结肠癌模型,且无手术相关并发症或死亡。在第3周时,在荧光镜下观察到所有模型动物均有表达GFP的原发性肿瘤,同时通过荧光成像监测到两个转移性肿瘤。肿瘤体积随时间逐渐增大。15只肿瘤移植小鼠中有7只死亡,主要死亡原因是恶性肿瘤生长导致的肠梗阻和恶病质。实验结束时8只模型动物存活,其中6只发生转移(6例转移至肠系膜淋巴结,4例肝转移,2例胰腺转移,1例纵隔淋巴结转移)。我们的结果表明,我们的GFP标记结肠癌原位移植模型成功率高且实用;移植肿瘤表现出与人类结直肠癌相似的生物学特性,可用于对肿瘤细胞生长和转移进行实时、体内、非侵入性动态观察和分析。

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