Murine portal vein catheterization to analyze liver-directed therapies.
Murine portal vein catheterization to analyze liver-directed therapies.
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DOI：
10.1016/j.jss.2013.06.051
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发表时间：
2013-12
影响因子：
2.2
通讯作者：
Evers, B. Mark
中科院分区：
文献类型：
--
作者：
Valentino, Joseph D.;Rychahou, Piotr G.;Mustain, W. Conan;Elliott, Victoria A.;Evers, B. Mark
小干扰RNA（siRNA）提供了一种高度选择性的方法来靶向突变的途径;然而，它的使用由于特异性递送到肿瘤细胞而变得复杂。本研究的目的是：i）开发用于向肝转移慢性递送治疗剂的门静脉导管插入术（PVC）的新型鼠模型，ii）确定向肝转移局部递送siRNA的益处，以及iii）确定上皮细胞粘附分子（EpCAM）作为向结肠直肠癌（CRC）转移递送siRNA的选择性靶标的效用。i）在2月龄Balb/C小鼠中通过中线剖腹术进行PVC。ii）使用荧光标记的微球评价门静脉血流分布和导管通畅性。通过脾脏注射CT 26鼠结肠癌细胞进行转移研究;通过IVIS成像评估DY-547标记的siRNA的摄取，并使用荧光显微镜证实转移的递送。iii）使用人组织微阵列的IHC染色评估EpCAM表达。i）通过盐水注射和超声确认成功的PVC。ii）微球的荧光成像证实了优异的分布和导管通畅性。门静脉注射DY 547标记的siRNA显示出整个肝脏中的高水平荧光，其中siRNA也在肝转移灶内被鉴定。iii）所有原发性CRC和肝转移瘤对EpCAM强烈染色，在正常肝细胞中没有表达。肝脏定向治疗提供了siRNA对CRC转移的选择性递送。EpCAM在CRC中的表达，而不是在正常肝脏中的表达，可以进一步选择性地靶向上皮来源的肝转移。
Small interfering RNA (siRNA) provides a highly selective method to target mutated pathways; however, its use is complicated by specific delivery to tumor cells. The aim of this study were to: i) develop a novel murine model of portal vein catheterization (PVC) for the chronic delivery of therapeutic agents to liver metastases, ii) determine the benefits of local delivery of siRNA to liver metastases, and iii) determine the utility of epithelial cell adhesion molecule (EpCAM) as a selective target for siRNA delivery to colorectal cancer (CRC) metastases. i) PVC was performed through midline laparotomy in 2 mo-old Balb/C mice. ii) Portal venous flow distribution and catheter patency were evaluated using fluorescently-labeled microspheres. Metastatic studies were performed by splenic injection of CT26 murine colon cancer cells; uptake of DY-547-labeled siRNA was assessed by IVIS imaging and delivery to metastases confirmed using fluorescent microscopy. iii) EpCAM expression was evaluated using IHC staining of human tissue microarrays. i) Successful PVC was confirmed by saline injection and ultrasound. ii) Fluorescent imaging of microspheres confirmed excellent distribution and catheter patency. Portal venous injection of DY547-labeled siRNA demonstrated a high level of fluorescence throughout the liver with siRNA also identified within the liver metastases. iii) All primary CRCs and liver metastases stained strongly for EpCAM with no expression in normal hepatocytes. Liver-directed therapy provides selective delivery of siRNA to CRC metastases. EpCAM expression in CRC, but not normal liver, may further selectively target hepatic metastases of epithelial origin.
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影响因子：
7.5
作者：
D'Angelica, Michael;Ammori, John;Shia, Jinru
通讯作者：
Shia, Jinru
影响因子：
13.5
作者：
Lo, CM;Ngan, H;Wong, J
通讯作者：
Wong, J
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
64.8
作者：
通讯作者：
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影响因子：
4.9
作者：
Leamon, Christopher P.;Reddy, Joseph A.;Wang, Yu
通讯作者：
Wang, Yu