Detection of pancreatic ductal adenocarcinoma in mice by ultrasound imaging of thymocyte differentiation antigen 1.
Detection of pancreatic ductal adenocarcinoma in mice by ultrasound imaging of thymocyte differentiation antigen 1.
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DOI：
10.1053/j.gastro.2013.06.011
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发表时间：
2013-10
期刊：
影响因子：
29.4
通讯作者：
Willmann JK
中科院分区：
文献类型：
--
作者：
Foygel K;Wang H;Machtaler S;Lutz AM;Chen R;Pysz M;Lowe AW;Tian L;Carrigan T;Brentnall TA;Willmann JK
胰腺导管腺癌（PDAC）的早期检测允许手术切除，并增加患者的生存时间。结合并放大肿瘤中新生血管蛋白信号的成像剂可以通过超声检测，从而能够准确检测小病变。我们寻找PDAC中新生血管的新标记物，并通过超声分子成像评估其用于肿瘤检测的潜力。胸腺细胞分化抗原1（Thy1）是通过蛋白质组学分析确定的PDAC新生血管的特异性生物标志物。PDAC的上调通过免疫组织化学分析来自28名健康个体、15名原发性慢性胰腺炎组织和196名PDAC的胰腺组织样本来验证。在培养的细胞中，在具有原位PDAC异种移植肿瘤的小鼠中，在新生血管上表达人Thy 1，以及在PDAC遗传小鼠模型的新生血管上，评估Thy 1靶向造影剂微泡的结合。基于免疫组化分析，Thy1在人PDAC血管中的水平显著高于慢性胰腺炎（P=.007）或正常组织样本（P<.0001）。在小鼠中，超声成像准确地检测到人类Thy1阳性PDAC异种移植物，以及PDAC遗传小鼠模型中表达内源性Thy1的PDAC。我们已经确定并验证了Thy1作为PDAC的标志物，可以通过超声分子成像在小鼠中检测到。特异性成像剂的开发和Thy1作为新生物标志物的鉴定可以帮助诊断这种癌症和患者的管理。
Early detection of pancreatic ductal adenocarcinoma (PDAC) allows for surgical resection and increases patient survival times. Imaging agents that bind and amplify the signal of neovascular proteins in neoplasms can be detected by ultrasound, enabling accurate detection of small lesions. We searched for new markers of neovasculature in PDAC and assessed their potential for tumor detection by ultrasound molecular imaging. Thymocyte Differentiation Antigen 1 (Thy1) was identified as a specific biomarker of PDAC neovasculature by proteomic analysis. Upregulation in PDAC was validated by immunohistochemical analysis of pancreatic tissue samples from 28 healthy individuals, 15 with primary chronic pancreatitis tissues, and 196 with PDAC. Binding of Thy1-targeted contrast microbubbles was assessed in cultured cells, in mice with orthotopic PDAC xenograft tumors expressing human Thy1 on the neovasculature, and on the neovasculature of a genetic mouse model of PDAC. Based on immunohistochemical analyses, levels of Thy1 were significantly higher in the vascular of human PDAC than chronic pancreatitis (P=.007) or normal tissue samples (P<.0001). In mice, ultrasound imaging accurately detected human Thy1-positive PDAC xenografts, as well as PDACs that express endogenous Thy1 in genetic mouse models of PDAC. We have identified and validated Thy1 as a marker of PDAC that can be detected by ultrasound molecular imaging in mice. The development of a specific imaging agent and identification of Thy1 as a new biomarker could aid in the diagnosis of this cancer and management of patients.
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影响因子：
3.7
作者：
Baine MJ;Chakraborty S;Smith LM;Mallya K;Sasson AR;Brand RE;Batra SK
通讯作者：
Batra SK
影响因子：
7.5
作者：
Chen, X;Higgins, J;So, S
通讯作者：
So, S
影响因子：
14.8
作者：
Laib, Anna M.;Bartol, Arne;Augustin, Hellmut G.
通讯作者：
Augustin, Hellmut G.
影响因子：
3.3
作者：
Iozzelli, Andrea;D'Orta, Giovanni;Sardanelli, Francesco
通讯作者：
Sardanelli, Francesco
DOI：
10.1002/biof.41
发表时间：
2009-05
期刊：
BioFactors (Oxford, England)
影响因子：
--
作者：
Bradley JE;Ramirez G;Hagood JS
通讯作者：
Hagood JS