Evidence map›Paper›PMID 26203823›Full record

ArticleNature protocols2015

An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis.

Thomas Reiberger, Yunching Chen, Rakesh R Ramjiawan, Tai Hato, Christopher Fan, Rekha Samuel, Sylvie Roberge, Peigen Huang, Gregory Y Lauwers, Andrew X Zhu and 3 more

Open access · greenAbstract read
In one paragraph

Article in Nature protocols, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

79 citing papers in PubMed, 117 citations in OpenAlex.

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  15. Precision models in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025
    Review
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19 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

13 authors at 2 institutions in 1 country.

Thomas Reiberger1] Department of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
Yunching Chen1] Department of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Rakesh R Ramjiawan1] Department of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Angiogenesis Laboratory, Cancer Center Amsterdam, Department of Medical Oncology, Vrije Universiteit (VU) University Medical Center, Amsterdam, the Netherlands.
Tai HatoDepartment of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Christopher Fan1] Department of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Duke University School of Medicine, Durham, North Carolina, USA.
Rekha SamuelDepartment of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Sylvie RobergeDepartment of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Peigen HuangDepartment of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Gregory Y LauwersDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Andrew X ZhuDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Nabeel BardeesyDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Rakesh K JainDepartment of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Dan G DudaDepartment of Radiation Oncology, Steele Laboratories for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Harvard University · USMassachusetts General Hospital · US

Funding

Vascular Normalization: Rolse of Perivascular CellsP01CA080124 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2000 to 2016
$35.0M
Probing Tumor Microenvironment Using NanotechnologyR01CA126642 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2008 to 2012
$8.3M
Role of SDF1a pathway in prostate cancer relapse and metastasis post-radiotherapyR01CA159258 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DUDA, DAN GABRIEL · 2011 to 2015
$1.6M
Visualizing Immune Responses in vivo: a systems biology approachR21CA139168 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DUDA, DAN GABRIEL · 2009 to 2010
$412k
Austrian Science Fund FWF J 3618Howard Hughes Medical InstituteNCI NIH HHS P01 CA080124NCI NIH HHS P01-CA080124NCI NIH HHS R01 CA126642NCI NIH HHS R01-CA126642NCI NIH HHS R01 CA159258NCI NIH HHS R01-CA159258NCI NIH HHS R21 CA139168NCI NIH HHS R21-CA139168
6 · The paper itself

Abstract

Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4(-/-)Stk3(F/-) (also known as Mst1(-/-)Mst2(F/-); F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsLiver Neoplasms, ExperimentalAnimalsCarbon TetrachlorideLiver CirrhosisMice, Inbred C3HTransplantation, HeterologousCarbon Tetrachloride

Identifiers

PMID26203823
PMCPMC4800979
OpenAlexW1905968574

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Registered trials

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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.