文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

胆管癌和原发性硬化性胆管炎中的白细胞介素-6/Janus激酶/信号转导和转录激活因子3轴：通过患者来源的类器官解锁治疗策略

The IL-6/JAK/STAT3 Axis in Cholangiocarcinoma and Primary Sclerosing Cholangitis: Unlocking Therapeutic Strategies Through Patient-Derived Organoids.

作者信息

Boden Corinna, Esser Laura K, Dold Leona, Langhans Bettina, Zhou Taotao, Kaczmarek Dominik J, Gonzalez-Carmona Maria A, Weismüller Tobias J, Kristiansen Glen, Kalff Jörg C, Hölzel Michael, Matthaei Hanno, Toma Marieta I, Branchi Vittorio

机构信息

Department of General, Abdominal, Thoracic and Vascular Surgery, University Hospital Bonn, 53127 Bonn, Germany.

Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany.

出版信息

Biomedicines. 2025 Apr 29;13(5):1083. doi: 10.3390/biomedicines13051083.

DOI:10.3390/biomedicines13051083
PMID:40426911
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12108797/
Abstract

Primary sclerosing cholangitis (PSC) is a rare, incurable liver disease characterized by chronic biliary inflammation and fibrosis. PSC is a significant risk factor for biliary tract cancer (BTC). This study aims to evaluate STAT3 expression in BTC and its prognostic significance as well as explore the potential of organoids derived from PSC and liver tumor patients as an in vitro model for testing novel therapeutic strategies in both PSC and BTC. Fresh tissue samples obtained from 10 PSC patients through targeted endoscopic retrograde cholangiography (ERC) and biopsy samples from liver tumor patients were used to establish organoid cultures. Organoids were treated with different agents and the therapeutic effect was measured by CellTiterGlo. Treatment with the JAK inhibitor baricitinib was followed by the measurement of cytokine concentrations in the supernatant. Archived formalin-fixed paraffin-embedded (FFPE) samples from 55 surgically resected BTC tumors were analyzed for STAT3 expression using immunohistochemistry. We successfully established organoid cultures from all ERC samples. STAT3 protein expression was detected in 56% of tumor samples and 69% of the immune microenvironment. STAT3 positivity in the immune cell compartment was associated with longer disease-free survival, although the multivariate analysis could not confirm its value as an independent prognostic factor. Chemotherapy testing on liver tumor organoids showed various degrees of decreases in viability after treatment with gemcitabine, cisplatin, and cabozantinib. Baricitinib treatment significantly reduced IL-6 and MCP-1 secretion in cholangiocarcinoma The patient-derived organoid model of PSC and liver tumors is a valuable tool for testing novel and established therapeutic strategies, including JAK inhibitors and chemotherapy regimens. STAT3 expression in the immune microenvironment of BTC may serve as a prognostic marker. Further studies are needed to explore the integration of co-cultured organoid systems with stromal and immune components to improve physiological relevance.

摘要

原发性硬化性胆管炎（PSC）是一种罕见的、无法治愈的肝脏疾病，其特征为慢性胆管炎症和纤维化。PSC是胆管癌（BTC）的一个重要危险因素。本研究旨在评估STAT3在BTC中的表达及其预后意义，并探索源自PSC和肝肿瘤患者的类器官作为体外模型用于测试PSC和BTC新型治疗策略的潜力。通过靶向内镜逆行胆管造影（ERC）从10例PSC患者获得的新鲜组织样本以及肝肿瘤患者的活检样本用于建立类器官培养。类器官用不同药物处理，并用CellTiterGlo测量治疗效果。用JAK抑制剂巴瑞替尼处理后，测量上清液中的细胞因子浓度。使用免疫组织化学分析55例手术切除的BTC肿瘤的存档福尔马林固定石蜡包埋（FFPE）样本中的STAT3表达。我们成功地从所有ERC样本中建立了类器官培养。在56%的肿瘤样本和69%的免疫微环境中检测到STAT3蛋白表达。免疫细胞区室中的STAT3阳性与更长的无病生存期相关，尽管多变量分析不能确认其作为独立预后因素的价值。对肝肿瘤类器官的化疗测试显示，用吉西他滨、顺铂和卡博替尼处理后活力有不同程度的降低。巴瑞替尼治疗显著降低胆管癌中IL-6和MCP-1的分泌。源自PSC和肝肿瘤患者的类器官模型是测试新型和既定治疗策略（包括JAK抑制剂和化疗方案）的有价值工具。BTC免疫微环境中的STAT3表达可能作为一种预后标志物。需要进一步研究探索将共培养类器官系统与基质和免疫成分整合以提高生理相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/b1404ae64ccc/biomedicines-13-01083-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/c35b18e7299d/biomedicines-13-01083-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/bf1f2353329a/biomedicines-13-01083-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/982297ec5f08/biomedicines-13-01083-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/b1404ae64ccc/biomedicines-13-01083-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/c35b18e7299d/biomedicines-13-01083-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/bf1f2353329a/biomedicines-13-01083-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/982297ec5f08/biomedicines-13-01083-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc5/12108797/b1404ae64ccc/biomedicines-13-01083-g004.jpg

相似文献

[1]
The IL-6/JAK/STAT3 Axis in Cholangiocarcinoma and Primary Sclerosing Cholangitis: Unlocking Therapeutic Strategies Through Patient-Derived Organoids.

Biomedicines. 2025-4-29

[2]
Expression of the large amino acid transporter SLC7A5/LAT1 on immune cells is enhanced in primary sclerosing cholangitis-associated cholangiocarcinoma and correlates with poor prognosis in cholangiocarcinoma.

Hum Pathol. 2024-11

[3]
Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities.

Hepatology. 2020-10

[4]
Transposon-based oncogene integration in Abcb4(Mdr2) mice recapitulates high susceptibility to cholangiocarcinoma in primary sclerosing cholangitis.

J Hepatol. 2025-1

[5]
Cholangiocarcinoma cell proliferation is enhanced in primary sclerosing cholangitis: A role for IL-17A.

Int J Cancer. 2023-6-15

[6]
Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis.

Hepatol Commun. 2024-7-1

[7]
Single-Cell Transcriptomic Profiling of Cholangiocyte Organoids Derived from Bile Ducts of Primary Sclerosing Cholangitis Patients.

Dig Dis Sci. 2024-10

[8]
Surveillance of primary sclerosing cholangitis with ERC and brush cytology: risk factors for cholangiocarcinoma.

Scand J Gastroenterol. 2017-2

[9]
Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis.

J Hepatol. 2021-9

[10]
Suspicious brush cytology is an indication for liver transplantation evaluation in primary sclerosing cholangitis.

World J Gastroenterol. 2017-9-7

引用本文的文献

[1]
The application of organoids in treatment decision-making for digestive system cancers: progress and challenges.

Mol Cancer. 2025-8-25

[2]
Applications of 3D models in cholangiocarcinoma.

Front Oncol. 2025-7-31

本文引用的文献

[1]
Tumor-derived CCL2 drives tumor growth and immunosuppression in IDH1- mutant cholangiocarcinoma.

Hepatology. 2024-12-3

[2]
JAK inhibitors (JAKi): Mechanisms of action and perspectives in systemic and autoimmune diseases.

Rev Med Interne. 2025-2

[3]
Environmental Risk Factors for Gallbladder Cancer: Field-Wide Systematic Review and Meta-Analysis.

Clin Gastroenterol Hepatol. 2024-10-5

[4]
IL-17 signaling in primary sclerosing cholangitis patient-derived organoids.

Hepatol Commun. 2024-6-1

[5]
Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

CA Cancer J Clin. 2024

[6]
Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.

J Exp Clin Cancer Res. 2024-1-20

[7]
IL-6-Dependent STAT3 Activation and Induction of Proinflammatory Cytokines in Primary Sclerosing Cholangitis.

Clin Transl Gastroenterol. 2023-8-1

[8]
Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

Ann Oncol. 2023-2

[9]
Inflammatory pathways and cholangiocarcinoma risk mechanisms and prevention.

Adv Cancer Res. 2022

[10]
Cholangiocarcinoma.

Nat Rev Dis Primers. 2021-9-9

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索