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建立侵袭性胰胆管细胞癌患者来源的临床前模型。

Establishment of Patient-derived Preclinical Models for Invasive Papillary Cholangiocarcinoma.

机构信息

Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.

Division of Convergence Technology, Research Institute of National Cancer Center, Goyang, Republic of Korea.

出版信息

Anticancer Res. 2022 Jan;42(1):599-608. doi: 10.21873/anticanres.15517.

DOI:10.21873/anticanres.15517
PMID:34969769
Abstract

BACKGROUND/AIM: Invasive papillary cholangio-carcinoma (IPC) is a minor subtype of extrahepatic cholangiocarcinoma. However, its etiology and characteristics remain unknown because of the unavailability of in vitro and in vivo models. We aimed to establish a novel preclinical model for translational research of IPC.

MATERIALS AND METHODS

A patient-derived xenograft (PDX) was engrafted in NOG mice and the cell line National Cancer Center human IPC (NCChIPC) was subsequently established from the PDX tumors. Immunohistochemistry and RNA-sequencing were used to determine the retention of original characteristics of patient tissues.

RESULTS

PDX tumors showed successful amplification, and the NCChIPC-derived xenograft largely retained the histopathological features of the original tumor with CK19, MUC1 and MUC5AC expression. Transcriptome analysis showed a high correlation between patient and preclinical models. Additionally, anticancer drugs response was analyzed in the NCChIPC PDX.

CONCLUSION

These novel preclinical models here will help elucidate IPC etiology and facilitate translational research.

摘要

背景/目的:浸润性乳头状胆管癌(IPC)是肝外胆管癌的一种少见亚型。然而,由于缺乏体外和体内模型,其病因和特征仍不清楚。我们旨在建立一种新的用于 IPC 转化研究的临床前模型。

材料和方法

将患者来源的异种移植物(PDX)植入 NOG 小鼠中,随后从 PDX 肿瘤中建立了国家癌症中心人类 IPC(NCChIPC)细胞系。免疫组织化学和 RNA 测序用于确定患者组织原始特征的保留情况。

结果

PDX 肿瘤成功扩增,NCChIPC 衍生的异种移植物在 CK19、MUC1 和 MUC5AC 表达方面很大程度上保留了原始肿瘤的组织病理学特征。转录组分析显示患者和临床前模型之间具有高度相关性。此外,还在 NCChIPC PDX 中分析了抗癌药物的反应。

结论

这些新的临床前模型将有助于阐明 IPC 的病因,并促进转化研究。

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