Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment
Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment
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DOI：
10.1038/srep04410
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发表时间：
2014-03-19
影响因子：
4.6
通讯作者：
Logsdon, Craig D.
中科院分区：
文献类型：
--
作者：
Cruz-Monserrate, Zobeida;Roland, Christina L.;Logsdon, Craig D.
胰腺导管腺癌（PDAC）是美国癌症死亡的第四大原因，每年约有40，000人死亡。PDAC预后差主要是由于诊断较晚。目前，PDAC最敏感的诊断需要侵入性手术，如内窥镜超声检查，其具有固有的风险和高度依赖于操作者的准确性。在这里，我们利用了实体瘤的一般特征，即作为代谢副产物产生的酸性微环境，开发了一种使用pH（低）插入肽（pHLIPs）进行PDAC成像的新方法。我们表明，荧光标记的pHLIPs可以本地化和特异性检测PDAC在人类异种移植以及PDAC和PanIN病变的基因工程小鼠模型。这种新的方法可以提高PDAC的检测，鉴别诊断和分期。
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for similar to 40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.