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在原位裸鼠模型中,MUC1可选择性地靶向人类胰腺癌。

MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

作者信息

Park Jeong Youp, Hiroshima Yukihiko, Lee Jin Young, Maawy Ali A, Hoffman Robert M, Bouvet Michael

机构信息

Department of Surgery, University of California San Diego, San Diego, California, United States of America; AntiCancer, Inc., San Diego, California, United States of America; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Department of Surgery, University of California San Diego, San Diego, California, United States of America; AntiCancer, Inc., San Diego, California, United States of America; Department of Surgery, Yokohama City University Graduate School of Medicine, Yokohama City, Japan.

出版信息

PLoS One. 2015 Mar 27;10(3):e0122100. doi: 10.1371/journal.pone.0122100. eCollection 2015.

Abstract

The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2) antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

摘要

本研究的目的是确定与荧光团偶联的MUC1抗体是否可用于可视化胰腺癌。抗MUC1(CT2)抗体与550 nm或650 nm荧光团偶联。使用裸鼠制作胰腺癌的皮下和原位模型。蛋白质免疫印迹和流式细胞术分析证实了MUC1在包括BxPC-3和Panc-1在内的人胰腺癌细胞系中的表达。用荧光团偶联的抗MUC1抗体进行免疫细胞化学检测,显示Panc-1癌细胞膜上有荧光区域。经尾静脉注射偶联的抗MUC1抗体后,皮下移植的Panc-1和BxPC-3肿瘤发出强烈的荧光信号。在皮下肿瘤模型中,在肿瘤边缘和细胞之间的间隙处可观察到偶联的抗MUC1抗体发出的荧光信号。在原位移植的Panc-1和BxPC-3模型中,偶联的抗MUC1抗体与肿瘤结合,从而能够对肿瘤进行成像。本研究表明,荧光团偶联的抗MUC1抗体可在体外和体内使胰腺肿瘤可视化,可能有助于改善胰腺癌的诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d8/4376872/c7dea5706fff/pone.0122100.g001.jpg

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