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胆管癌的体外向神经生长:一项实验研究。

In vitro neuraotropic growth of cholangiocarcinoma: an experimental study.

作者信息

Wang Yu-Xue, Liu Wei, Tan Xin-Yu, Tang Hui-Huan

机构信息

Department of Emergency Medicine, Xiang Ya Hospital, Central South University, Changsha 410008, China.

出版信息

JRSM Short Rep. 2013 Sep 13;4(10):2042533313476690. doi: 10.1177/2042533313476690. eCollection 2013.

DOI:10.1177/2042533313476690
PMID:24319575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3831859/
Abstract

OBJECTIVE

Perineural invasion of cholangiocarcinoma happens in the early stage of the disease but is often not recognized until its later stages. Research about the behaviour and mechanism of perineural invasion by cholangiocarcinoma is urgently needed for a useful new model. The aim of this work is to establish a novel model to address the problem.

DESIGN

Neural cells and cholangiocarcinoma cells were co-cultured to mimic the neurotropic invasion of cholangiocarcinoma.

SETTING

Human embryonic stem cells were induced to form neural cells by glial cell-derived neurotropic factor and retinoic acid; neural cells and cholangiocarcinoma cells were co-cultured in Transwell chamber.

PARTICIPANTS

Human embryonic stem cells and cholangiocarcinoma cells were applied.

MAIN OUTCOME MEASURES

Paired t-test was used to compare the counts of penetrating cholangiocarcinoma cells in co-culture and control group.

RESULTS

Formation of neurospheres and neural-like cells were observed following induction at 24 and 48 h, respectively; synapses were viewed to protrude from neural-like cell bodies after incubation for 96 h. Forty-eight hours after incubation, immunocytochemical staining of the cells showed that synaptophysin and glial fibrillary acidic protein were expressed in the neuron-like cells and gliocytes-like cells, respectively. The cholangiocarcinoma cells that had penetrated through the Matrigel/polyethylene terephthalate membrane from the upper chamber to the lower chamber of the Transwell in the co-culture group were significantly more numerous than those in the control group (68 ± 8.3/field versus 46 ± 5.7/field, P < 0.05).

CONCLUSION

The novel model is a valuable tool to study the perineural invasion of cholangiocarcinoma.

摘要

目的

胆管癌的神经周围浸润在疾病早期就会发生,但往往直到晚期才被发现。迫切需要研究胆管癌神经周围浸润的行为和机制,以建立一个有用的新模型。这项工作的目的是建立一个新模型来解决这个问题。

设计

将神经细胞和胆管癌细胞共培养,以模拟胆管癌的嗜神经侵袭。

设置

通过胶质细胞源性神经营养因子和视黄酸诱导人胚胎干细胞形成神经细胞;神经细胞和胆管癌细胞在Transwell小室中共培养。

参与者

应用人胚胎干细胞和胆管癌细胞。

主要观察指标

采用配对t检验比较共培养组和对照组中穿透胆管癌细胞的数量。

结果

分别在诱导24小时和48小时后观察到神经球和神经样细胞的形成;培养96小时后,可见突触从神经样细胞体中突出。培养48小时后,细胞免疫细胞化学染色显示,突触素和胶质纤维酸性蛋白分别在神经元样细胞和胶质细胞样细胞中表达。共培养组中从Transwell上室穿过基质胶/聚对苯二甲酸乙二酯膜进入下室的胆管癌细胞明显多于对照组(68±8.3/视野对46±5.7/视野,P<0.05)。

结论

该新模型是研究胆管癌神经周围浸润的有价值工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d51/3831859/5cff18e306fd/10.1177_2042533313476690-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d51/3831859/ca6a7fa1a782/10.1177_2042533313476690-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d51/3831859/286b3fd3898f/10.1177_2042533313476690-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d51/3831859/5cff18e306fd/10.1177_2042533313476690-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d51/3831859/ca6a7fa1a782/10.1177_2042533313476690-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d51/3831859/286b3fd3898f/10.1177_2042533313476690-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d51/3831859/5cff18e306fd/10.1177_2042533313476690-fig3.jpg

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本文引用的文献

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Muscarinic acetylcholine receptor M3 in proliferation and perineural invasion of cholangiocarcinoma cells.毒蕈碱型乙酰胆碱受体 M3 在胆管癌细胞增殖和周围神经侵犯中的作用。
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Basic fibroblast growth factor induces cholangiocarcinoma cell migration via activation of the MEK1/2 pathway.碱性成纤维细胞生长因子通过激活MEK1/2信号通路诱导胆管癌细胞迁移。
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Fatty acid-binding protein 5 promotes cell proliferation and invasion in human intrahepatic cholangiocarcinoma.
脂肪酸结合蛋白 5 促进人肝内胆管癌的细胞增殖和侵袭。
Oncol Rep. 2012 Oct;28(4):1283-92. doi: 10.3892/or.2012.1922. Epub 2012 Jul 19.
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Periostin activates integrin α5β1 through a PI3K/AKT‑dependent pathway in invasion of cholangiocarcinoma.骨粘连蛋白通过 PI3K/AKT 依赖性途径激活整合素 α5β1 促进胆管癌细胞侵袭。
Int J Oncol. 2012 Sep;41(3):1110-8. doi: 10.3892/ijo.2012.1530. Epub 2012 Jun 25.
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Angiotensin II enhances epithelial-to-mesenchymal transition through the interaction between activated hepatic stellate cells and the stromal cell-derived factor-1/CXCR4 axis in intrahepatic cholangiocarcinoma.血管紧张素 II 通过激活的肝星状细胞与基质细胞衍生因子-1/CXCR4 轴的相互作用增强肝内胆管癌中的上皮间质转化。
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Combining cetuximab with killer lymphocytes synergistically inhibits human cholangiocarcinoma cells in vitro.西妥昔单抗联合杀伤性淋巴细胞协同抑制人胆管癌细胞的体外研究。
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Neoplasma. 2012;59(4):409-15. doi: 10.4149/neo_2012_053.
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Targeted drug regulation on methylation of p53-BAX mitochondrial apoptosis pathway affects the growth of cholangiocarcinoma cells.靶向药物对p53 - BAX线粒体凋亡通路甲基化的调控影响胆管癌细胞的生长。
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