Rat N-ERC/mesothelin as a marker for in vivo screening of drugs against pancreas cancer.

Rat N-ERC/mesothelin as a marker for in vivo screening of drugs against pancreas cancer.
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DOI:
10.1371/journal.pone.0111481
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Tsuda H
Tsuda H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fukamachi K;Iigo M;Hagiwara Y;Shibata K;Futakuchi M;Alexander DB;Hino O;Suzui M;Tsuda H

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胰腺导管腺癌(PDA)是一种高致死率的疾病,通常在晚期被诊断出来。我们建立了携带由Cre/loxP激活控制的突变K-ras基因的转基因大鼠。动物的PDA在组织病理学上与人类相似。之前,我们报道了患PDA的大鼠血清N-ERC/间皮素水平显著高于对照组。在本研究中,为了确定血清N-ERC/间皮素水平是否与肿瘤大小相关,我们测量了患PDA大鼠的N-ERC/间皮素水平。血清N-ERC/间皮素水平升高与肿瘤大小增大相关。提示血清N-ERC/间皮素水平与肿瘤大小之间存在相关性。我们接下来研究了化疗对血清N-ERC/间皮素水平的影响。将大鼠胰腺癌细胞皮下植入NOD-SCID小鼠侧腹。与对照组相比,200 mg/kg吉西他滨组小鼠肿瘤重量和血清N-ERC/间皮素水平显著降低。这些结果表明血清N-ERC/间皮素测量可能对监测治疗反应有用。
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease, which is usually diagnosed in an advanced stage. We have established transgenic rats carrying a mutated K-ras gene controlled by Cre/loxP activation. The animals develop PDA which is histopathologically similar to that in humans. Previously, we reported that serum levels of N-ERC/mesothelin were significantly higher in rats bearing PDA than in controls. In the present study, to determine whether serum levels of N-ERC/mesothelin correlated with tumor size, we measured N-ERC/mesothelin levels in rats bearing PDA. Increased serum levels of N-ERC/mesothelin correlated with increased tumor size. This result indicates an interrelationship between the serum level of N-ERC/mesothelin and tumor size. We next investigated the effect of chemotherapy on serum N-ERC/mesothelin levels. Rat pancreatic cancer cells were implanted subcutaneously into the flank of NOD-SCID mice. In the mice treated with 200 mg/kg gemcitabine, tumor weight and the serum level of N-ERC/mesothelin were significantly decreased compared to controls. These results suggest that serum N-ERC/mesothelin measurements might be useful for monitoring response to therapy.
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