Evidence map›Paper›PMID 25454978›Full record

ArticleThe Journal of surgical research2015

Ablation of 5-lipoxygenase mitigates pancreatic lesion development.

Lawrence M Knab, Michelle Schultz, Daniel R Principe, Windel E Mascarinas, Elias Gounaris, Hidayatullah G Munshi, Paul J Grippo, David J Bentrem

Open access · greenAbstract read
In one paragraph

Article in The Journal of surgical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
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

9 citing papers in PubMed, 19 citations in OpenAlex.

  1. Controlled Self-Immolative Release of β-Lapachone via an OptimizedJournal of the American Chemical Society · 2025
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Leukotrienes in Tumor-Associated Inflammation.Frontiers in pharmacology · 2020
    Review
  7. CharacterisingGut · 2018
    Article
  8. The yin and yang of leukotriene BSeminars in immunology · 2017
    Review
  9. Review
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

8 authors at 2 institutions in 1 country.

Lawrence M KnabDivision of Surgical Oncology, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: l-knab@northwestern.edu.
Michelle SchultzDepartment of Medicine, University of Illinois-Chicago, Chicago, Illinois.
Daniel R PrincipeRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.
Windel E MascarinasDepartment of Medicine, University of Illinois-Chicago, Chicago, Illinois.
Elias GounarisRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.
Hidayatullah G MunshiDivision of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Surgery, Jesse Brown VA Medical Center, Chicago, Illinois.
Paul J GrippoDepartment of Medicine, University of Illinois-Chicago, Chicago, Illinois.
David J BentremDivision of Surgical Oncology, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Surgery, Jesse Brown VA Medical Center, Chicago, Illinois.
Northwestern University · USUniversity of Illinois Chicago · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Non Invasive Treatment Response Monitoring and molecular characterization of NSCLC using Cell-free DNA isolated by an AC Electrokinetic DeviceR01CA161283 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GRIPPO, PAUL J · 2012 to 2016
$1.8M
Omega-6 Fat Promotion of Mutant Kras-Induced Pancreatic NeoplasiaR21CA123041 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GRIPPO, PAUL J · 2007 to 2008
$332k
NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA161283NCI NIH HHS R01 CA161283-01NCI NIH HHS R21 CA123041NCI NIH HHS R21 CA123041-01
6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC), which continues to have a dismal prognosis, is associated with a pronounced fibroinflammatory response. Inflammation in vivo can be mediated by 5-lipoxygenase (5LO), an enzyme that converts omega-6 fatty acids (FA) to eicosanoids, including leukotriene B4 (LTB4). We have previously shown that diets rich in omega-6 FA increase pancreatic lesions and mast cell infiltration in EL-Kras mice. In this study, we evaluated the role of 5LO in generating higher levels of LTB4 from human cells and in mediating lesion development and mast cell infiltration in EL-Kras mice. MATERIALS AND

methodsHuman pancreatic ductal epithelial and cancer cells were treated with omega-6 FA in vitro. EL-Kras mice lacking 5LO (EL-Kras/5LO(-/-)) mice were generated and fed standard chow or omega-6 FA diets. Pancreatic lesion frequency and mast cell infiltration were compared with EL-Kras/5LO(+/+) mice. Human PDAC tumors were evaluated for 5LO expression and mast cells.

resultsHuman pancreatic ductal epithelial and pancreatic cancer cells treated with omega-6 FA generated increased LTB4 levels in vitro. EL-Kras/5LO(-/-) mice developed fewer pancreatic lesions and had decreased mast cell infiltration when compared with EL-Kras/5LO(+/+) mice. Human PDAC tumors with increased 5LO expression demonstrate increased mast cell infiltration. Additionally, diets rich in omega-6 FA failed to increase pancreatic lesion development and mast cell infiltration in EL-Kras/5LO(-/-) mice.

conclusionsThe expansion of mutant Kras-induced lesions via omega-6 FA is dependent on 5LO, and 5LO functions downstream of mutant Kras to mediate inflammation, suggesting that 5LO may be a potential chemopreventive and therapeutic target in pancreatic cancer.

Indexed as

AnimalsArachidonate 5-LipoxygenaseCarcinoma, Pancreatic DuctalCell Line, TumorFatty Acids, Omega-6FemaleHumansLeukotriene B4Mast CellsMice, Inbred C57BLMice, TransgenicPancreatic NeoplasmsTumor MicroenvironmentArachidonate 5-LipoxygenaseFatty Acids, Omega-6Leukotriene B45-LipoxygenaseInflammationOmega-6 fatty acidsPancreatic cancer

Identifiers

PMID25454978
PMCPMC4843112
OpenAlexW2141497277

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.