Evidence map›Paper›PMID 27122661›Full record

ArticleWorld journal of gastroenterology2016

Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease.

Aditya Ambade, Abhishek Satishchandran, Benedek Gyongyosi, Patrick Lowe, Gyongyi Szabo

Open access · hybridAbstract read
In one paragraph

Article in World journal of gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

35 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Review
  5. Article
  6. Impact of binge drinking on alcoholic liver disease.Archives of pharmacal research · 2025
    Review
  7. Article
  8. Article
  9. Experimental In Vivo Toxicity Models for Alcohol Toxicity.The Eurasian journal of medicine · 2023
    Article
  10. Article
  11. Review
  12. Isorhamnetin exerts anti-tumor activity in DEN + CClMedical oncology (Northwood, London, England) · 2023
    Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
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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

5 authors at 1 institution in 1 country.

Aditya AmbadeAditya Ambade, Abhishek Satishchandran, Benedek Gyongyosi, Patrick Lowe, Gyongyi Szabo, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
Abhishek SatishchandranAditya Ambade, Abhishek Satishchandran, Benedek Gyongyosi, Patrick Lowe, Gyongyi Szabo, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
Benedek GyongyosiAditya Ambade, Abhishek Satishchandran, Benedek Gyongyosi, Patrick Lowe, Gyongyi Szabo, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
Patrick LoweAditya Ambade, Abhishek Satishchandran, Benedek Gyongyosi, Patrick Lowe, Gyongyi Szabo, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
Gyongyi SzaboAditya Ambade, Abhishek Satishchandran, Benedek Gyongyosi, Patrick Lowe, Gyongyi Szabo, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
University of Massachusetts Chan Medical School · US

Funding

Alcohol and Monocyte Signaling Administrative SupplementR01AA011576 · NIAAA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Gyongyi Szabo · 1998 to 2026
$9.3M
Medical Scientist Training at UMMS Administrative SupplementT32GM107000 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIEFE, CATARINA I. · 2013 to 2022
$4.9M
NIAAA NIH HHS R01 AA011576NIGMS NIH HHS T32 GM107000
6 · The paper itself

Abstract

aimTo establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD).

methodsAdult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA).

resultsAlcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed mice.

conclusionWe describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC.

Indexed as

Alanine Transaminasealpha-FetoproteinsAnimalsBiomarkers, TumorCarcinoma, HepatocellularCell ProliferationCytochrome P-450 CYP2E1DiethylnitrosamineEndotoxinsEthanolFatty Liver, AlcoholicHepatocytesImmunohistochemistryLiver Cirrhosis, AlcoholicLiver Neoplasms, ExperimentalMacrophage ActivationAlanine Transaminasealpha-FetoproteinsBiomarkers, TumorCytochrome P-450 CYP2E1DiethylnitrosamineEndotoxinsEthanolAlpha-fetoproteinLiver tumorMacrophage polarizationProliferating cell nuclear antigenSteatohepatitis

Identifiers

PMID27122661
PMCPMC4837428
OpenAlexW2344751387

What OpenQuestion holds

Textmetadata
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.