Evidence map›Paper›PMID 40993312›Full record

ArticleBritish journal of cancer2025

Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer.

Shohei Nogi, Shunsuke Kagawa, Atsuki Taniguchi, Tomohiko Yagi, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Kazuya Yasui, Tomokazu Fuji, Yoshiyasu Kono, Satoru Kikuchi and 5 more

Abstract read
In one paragraph

Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Shohei NogiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shunsuke KagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. skagawa@md.okayama-u.ac.jp.ORCID http://orcid.org/0000-0002-3610-8211
Atsuki TaniguchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Tomohiko YagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Nobuhiko KanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yoshihiko KakiuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kazuya YasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Tomokazu FujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yoshiyasu KonoDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Satoru KikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kosei TakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shinji KurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.ORCID http://orcid.org/0000-0002-4484-1253
Fuminori TeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hiroshi TazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.ORCID http://orcid.org/0000-0003-4658-1050
Toshiyoshi FujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) JP220K8873
6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear.

methodsWe investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin.

resultsNETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo.

conclusionsOur findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8-mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies.

Indexed as

Carcinoma, Pancreatic DuctalDeoxycytidineDrug Resistance, NeoplasmExtracellular TrapsInterleukin-8Pancreatic NeoplasmsReceptors, Interleukin-8AReceptors, Interleukin-8BAnimalsAntimetabolites, AntineoplasticCell Line, TumorFemaleGemcitabineHumansMaleMiceAntimetabolites, AntineoplasticCXCL8 protein, humanCXCR2 protein, humanDeoxycytidineGemcitabineInterleukin-8Receptors, Interleukin-8AReceptors, Interleukin-8B

Identifiers

PMID40993312
PMCPMC12644870

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.