Evidence map›Paper›PMID 34638465›Full record

ArticleCancers2021

DEN-Induced Rat Model Reproduces Key Features of Human Hepatocellular Carcinoma.

Keerthi Kurma, Olivier Manches, Florent Chuffart, Nathalie Sturm, Khaldoun Gharzeddine, Jianhui Zhang, Marion Mercey-Ressejac, Sophie Rousseaux, Arnaud Millet, Herve Lerat and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 70 citations in OpenAlex.

  1. Review
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  5. Dammarolic acid improves tyrosine kinase inhibitor activity in lung cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026
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  14. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Anti-carcinogenic effects and mechanisms of actions ofAmerican journal of cancer research · 2024
    Article
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

13 authors at 2 institutions in 1 country.

Keerthi KurmaUniversité Grenoble Alpes, 38000 Grenoble, France.
Olivier ManchesInstitute for Advanced Biosciences, Research Center Inserm U 1209/CNRS 5309, 38700 La Tronche, France.
Florent ChuffartUniversité Grenoble Alpes, 38000 Grenoble, France.
Nathalie SturmService d'Anatomo-Pathologie, Pôle de Biologie, CHU Grenoble Alpes, 38700 La Tronche, France.
Khaldoun GharzeddineUniversité Grenoble Alpes, 38000 Grenoble, France.
Jianhui ZhangUniversité Grenoble Alpes, 38000 Grenoble, France.
Marion Mercey-RessejacUniversité Grenoble Alpes, 38000 Grenoble, France.ORCID 0000-0003-0667-2513
Sophie RousseauxUniversité Grenoble Alpes, 38000 Grenoble, France.ORCID 0000-0001-5246-5350
Arnaud MilletUniversité Grenoble Alpes, 38000 Grenoble, France.ORCID 0000-0002-3547-7533
Herve LeratUniversité Grenoble Alpes, 38000 Grenoble, France.
Patrice N MarcheUniversité Grenoble Alpes, 38000 Grenoble, France.ORCID 0000-0002-8930-9340
Zuzana Macek JilkovaUniversité Grenoble Alpes, 38000 Grenoble, France.ORCID 0000-0002-2553-5971
Thomas DecaensUniversité Grenoble Alpes, 38000 Grenoble, France.ORCID 0000-0003-0928-0048
Centre National de la Recherche Scientifique · FRCentre Hospitalier Universitaire de Grenoble · FR

Funding

Fonds Agir pour les Maladies Chroniques 2017-2019La Ligue contre le cancer AURA 38
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The majority of HCC cases are associated with liver fibrosis or cirrhosis developing from chronic liver injuries. The immune system of the liver contributes to the severity of tissue damage, the establishment of fibrosis and the disease's progression towards HCC. Herein, we provide a detailed characterization of the DEN-induced HCC rat model during fibrosis progression and HCC development with a special focus on the liver's inflammatory microenvironment. Fischer 344 male rats were treated weekly for 14 weeks with intra-peritoneal injections of 50 mg/kg DEN. The rats were sacrificed before starting DEN-injections at 0 weeks, after 8 weeks, 14 weeks and 20 weeks after the start of DEN-injections. We performed histopathological, immunohistochemical, RT-qPCR, RNA-seq and flow cytometry analysis. Data were compared between tumor and non-tumor samples from the DEN-treated versus untreated rats, as well as versus human HCCs. Chronic DEN injections lead to liver damage, hepatocytes proliferation, liver fibrosis and cirrhosis, disorganized vasculature, and a modulated immune microenvironment that mimics the usual events observed during human HCC development. The RNA-seq results showed that DEN-induced liver tumors in the rat model shared remarkable molecular characteristics with human HCC, especially with HCC associated with high proliferation. In conclusion, our study provides detailed insight into hepatocarcinogenesis in a commonly used model of HCC, facilitating the future use of this model for preclinical testing.

Indexed as

DEN-induced rat modelHCChepatocarcinogenesisliver cancer

Identifiers

PMID34638465
PMCPMC8508319
OpenAlexW3203399559

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.