An animal model of preclinical diagnosis of pancreatic ductal adenocarcinomas
An animal model of preclinical diagnosis of pancreatic ductal adenocarcinomas
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DOI：
10.1016/j.bbrc.2009.10.019
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发表时间：
2009-12-18
影响因子：
3.1
通讯作者：
Tsuda, Hiroyuki
中科院分区：
文献类型：
--
作者：
Fukamachi, Katsumi;Tanaka, Hajime;Tsuda, Hiroyuki
胰腺导管腺癌（PDA）是一种高致死性疾病，通常在晚期才被诊断出来。反映人类状况的动物PDA模型对于开发早期诊断工具和探索新的治疗方法显然是必要的。我们已经建立了转基因大鼠携带突变的H-或K-ras基因（Hras 250和Kras 327）控制的Cre/loxP激活。这些动物发生的PDA在组织病理学上与人类相似。我们利用该模型来鉴定生物标志物以检测早期PDA。我们在这里报告，Erc/间皮素的血清水平显着高于在对照组的大鼠轴承PDA。重要的是，在肉眼可见的癌发展之前，大鼠中的水平显著升高。即使在具有非常小的显微镜下导管癌病变的大鼠中，也可以检测到升高的血清Erc/间皮素。我们相信这是第一个胰腺肿瘤动物模型的报告，其中症状前病变可以诊断。(C)2009 Elsevier Inc. All rights reserved.
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease, which is usually diagnosed in an advanced stage. Animal PDA models which reflect the human condition are clearly necessary to develop early diagnostic tools and explore new therapeutic approaches. We have established transgenic rats carrying a mutated H- or K-ras gene (Hras250 and Kras327) controlled by Cre/loxP activation. These animals develop PDA which are histopathologically similar to that in humans. We utilized this model to identify biomarkers to detect early PDA. We report here that serum levels of Erc/Mesothelin are significantly higher in rats bearing PDA than in controls. Importantly, the levels are significantly elevated in rats before grossly visible carcinomas develop. Even in rats with very small microscopic ductal carcinoma lesions, elevated serum Erc/Mesothelin can be detected. We believe this is the first report of a pancreas tumor animal model in which pre-symptomatic lesions can be diagnosed. (C) 2009 Elsevier Inc. All rights reserved.