Evidence map›Paper›PMID 18691550›Full record

ArticleCancer cell2008

Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis.

Toshiharu Sakurai, Guobin He, Atsushi Matsuzawa, Guann-Yi Yu, Shin Maeda, Gary Hardiman, Michael Karin

Abstract read
In one paragraph

Article in Cancer cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers.

0numbers the graph read from it
0cells of the map it votes in
271citing papers in PubMed
–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

271 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Targeting the MAPK Pathway in Cancer.International journal of molecular sciences · 2025
    Review
  7. Article
  8. NF-κB in inflammation and cancer.Cellular & molecular immunology · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

211 more citing papers are in PubMed but not listed here.

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

7 authors.

Toshiharu SakuraiLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Guobin He
Atsushi Matsuzawa
Guann-Yi Yu
Shin Maeda
Gary Hardiman
Michael Karin

Funding

Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Role of Inflammation in tumor promotion and progressionR01CA118165 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 2007 to 2016
$4.6M
Stress Signaling Pathways in Toxicity and DiseaseR01ES006376 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1993 to 2011
$4.3M
INTERACTIONS OF HEAVY METAL IONS WITH THE HUMAN GENOME R37ES004151 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1998 to 2007
$3.0M
INTERACTIONS OF HEAVY METAL IONS WITH THE HUMAN GENOMER01ES004151 · NIEHS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI KARIN, MICHAEL · 1985 to 1997
–
NCI NIH HHS CA118165NCI NIH HHS R01 CA118165NIDDK NIH HHS 1 P30 DK063491-03NIDDK NIH HHS P30 DK063491NIEHS NIH HHS ES004151NIEHS NIH HHS ES006376NIEHS NIH HHS ES0100337NIEHS NIH HHS R01 ES006376NIEHS NIH HHS R37 ES004151
6 · The paper itself

Abstract

Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species (ROS) and liver damage, whereas JNK1 activation promotes ROS accumulation, liver damage, and carcinogenesis. We examined whether hepatocyte p38 alpha, found to inhibit liver carcinogenesis, acts similarly to IKK beta in control of ROS metabolism and cell death. Hepatocyte-specific p38 alpha ablation enhanced ROS accumulation and liver damage, which were prevented upon administration of an antioxidant. In addition to elevated ROS accumulation, hepatocyte death, augmented by loss of either IKK beta or p38 alpha, was associated with release of IL-1 alpha. Inhibition of IL-1 alpha action or ablation of its receptor inhibited carcinogen-induced compensatory proliferation and liver tumorigenesis. IL-1 alpha release by necrotic hepatocytes is therefore an important mediator of liver tumorigenesis.

Indexed as

Oxidative StressAnimalsAntioxidantsCarcinogensCell DeathCell ProliferationDiethylnitrosamineEnzyme ActivationHeat-Shock ProteinsHepatocytesI-kappa B KinaseInterleukin-1alphaInterleukin-6JNK Mitogen-Activated Protein KinasesLiver NeoplasmsMiceAntioxidantsCarcinogensDdit3 protein, mouseDiethylnitrosamineHeat-Shock ProteinsHsbp1 protein, mouseI-kappa B KinaseInterleukin-1alphaInterleukin-6JNK Mitogen-Activated Protein KinasesMolecular ChaperonesNeoplasm Proteinsp38 Mitogen-Activated Protein KinasesReactive Oxygen SpeciesTranscription Factor CHOP

Identifiers

PMID18691550
PMCPMC2707922

What OpenQuestion holds

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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.