Evidence map›Paper›PMID 21386987›Full record

ArticlePloS one2011

Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction.

Daniel P Barry, Mohammad Asim, David A Leiman, Thibaut de Sablet, Kshipra Singh, Robert A Casero, Rupesh Chaturvedi, Keith T Wilson

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.4field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 39 citations in OpenAlex.

  1. Trial
  2. Pathogens (Basel, Switzerland) · 2024
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Chemoprevention Against Gastric Cancer.Gastrointestinal endoscopy clinics of North America · 2021
    Review
  10. Curcumin Oxidation Is Required for Inhibition ofFrontiers in cellular and infection microbiology · 2021
    Article
  11. Transformation ofPathogens (Basel, Switzerland) · 2020
    Review
  12. Article
  13. Article
  14. α-Difluoromethylornithine reduces gastric carcinogenesis by causing mutations inProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  15. Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Gut microbes, diet, and cancer.Cancer treatment and research · 2014
    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 3 institutions in 1 country.

Daniel P BarryDivision of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Mohammad Asim
David A Leiman
Thibaut de Sablet
Kshipra Singh
Robert A Casero
Rupesh Chaturvedi
Keith T Wilson
VA Tennessee Valley Healthcare System · USVanderbilt University Medical Center · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI MCGUINNESS, OWEN P · 1986 to 2011
$28.1M
Role of Iron and B-Catenin Activation in Gastric CarcinogenesisP01CA116087 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2009 to 2026
$27.5M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 1989 to 2026
$19.6M
THREE-TIERED PREVENTION MODEL TO BETTER SERVE ALL STUDENP30HD015052 · NICHD · VANDERBILT UNIVERSITY · PI DYKENS, ELISABETH MAY · 1985 to 2014
$18.6M
Project 3 - Molecular Signatures of Gastric Carcinogenesis in the Host Response to H. pyloriP01CA028842 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 1985 to 2019
$15.8M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
TRAINING IN GASTROENTEROLOGYT32DK007673 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 1992 to 2026
$8.4M
Spermine N1-Acetylase Induction in Lung CancersR01CA051085 · NCI · JOHNS HOPKINS UNIVERSITY · PI CASERO, ROBERT A. · 1990 to 2013
$4.7M
Immunomodulatory effects of arginine supplementation in colitis and colon cancerR01AT004821 · NCCIH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 2008 to 2017
$4.0M
NCCIH NIH HHS 3R01AT004821S1NCCIH NIH HHS R01 AT004821NCCIH NIH HHS R01AT004821NCI NIH HHS CA68485NCI NIH HHS P01 CA028842NCI NIH HHS P01CA028842NCI NIH HHS P01 CA116087NCI NIH HHS P01CA116087NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA051085NCI NIH HHS R01CA051085NCI NIH HHS R01 CA098454NCI NIH HHS R01CA098454NEI NIH HHS EY08126NEI NIH HHS P30 EY008126NICHD NIH HHS HD15052NICHD NIH HHS P30 HD015052NIDDK NIH HHS DK20593NIDDK NIH HHS DK58404NIDDK NIH HHS DK59637NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS P30DK058404NIDDK NIH HHS P60 DK020593NIDDK NIH HHS R01 DK053620NIDDK NIH HHS R01DK053620NIDDK NIH HHS T32 DK007673NIDDK NIH HHS T32DK007673NIDDK NIH HHS U24 DK059637
6 · The paper itself

Abstract

Helicobacter pylori infects half the world's population, and carriage is lifelong without antibiotic therapy. Current regimens prescribed to prevent infection-associated diseases such as gastroduodenal ulcers and gastric cancer can be thwarted by antibiotic resistance. We reported that administration of 1% D,L-α-difluoromethylornithine (DFMO) to mice infected with H. pylori reduces gastritis and colonization, which we attributed to enhanced host immune response due to inhibition of macrophage ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Although no ODC has been identified in any H. pylori genome, we sought to determine if DFMO has direct effects on the bacterium. We found that DFMO significantly reduced the growth rate of H. pylori in a polyamine-independent manner. Two other gram-negative pathogens possessing ODC, Escherichia coli and Citrobacter rodentium, were resistant to the DFMO effect. The effect of DFMO on H. pylori required continuous exposure to the drug and was reversible when removed, with recovery of growth rate in vitro and the ability to colonize mice. H. pylori exposed to DFMO were significantly shorter in length than those untreated and they contained greater internal levels of ATP, suggesting severe effects on bacterial metabolism. DFMO inhibited expression of the H. pylori virulence factor cytotoxin associated gene A, and its translocation and phosphorylation in gastric epithelial cells, which was associated with a reduction in interleukin-8 expression. These findings suggest that DFMO has effects on H. pylori that may contribute to its effectiveness in reducing gastritis and colonization and may be a useful addition to anti-H. pylori therapies.

Indexed as

AnimalsAntigens, BacterialBacterial ProteinsCells, CulturedEflornithineEnzyme InhibitorsGastric MucosaGastritisHelicobacter InfectionsHelicobacter pyloriHumansInterleukin-8MaleMiceMice, Inbred C57BLProtein TransportAntigens, BacterialBacterial ProteinscagA protein, Helicobacter pyloriEflornithineEnzyme InhibitorsInterleukin-8

Identifiers

PMID21386987
PMCPMC3046249
OpenAlexW2080194660

What OpenQuestion holds

Textmetadata
LicenceCC0
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.