Evidence map›Paper›PMID 33738839›Full record

ArticleHepatology (Baltimore, Md.)2021

Analysis and Validation of Human Targets and Treatments Using a Hepatocellular Carcinoma-Immune Humanized Mouse Model.

Yue Zhao, Jiaxu Wang, Wai Nam Liu, Shin Yie Fong, Timothy Wai Ho Shuen, Min Liu, Sarah Harden, Sue Yee Tan, Jia Ying Cheng, Wilson Wei Sheng Tan and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.5field-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

30 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Precision models in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  6. Article
  7. Article
  8. Review
  9. Single-cell RNA sequencing reveals anti-tumor potency of CD56Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  10. Small-molecule-based targeted therapy in liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. Fetal liver CD34Stem cell research & therapy · 2024
    Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. 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

17 authors at 5 institutions in 1 country.

Yue Zhao *Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.ORCID 0000-0003-2869-5257
Jiaxu Wang *Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.ORCID 0000-0001-7101-8230
Wai Nam LiuInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Shin Yie FongInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Timothy Wai Ho ShuenDivision of Medical Oncology, National Cancer Centre Singapore, Singapore.
Min LiuInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Sarah HardenInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Sue Yee TanInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Jia Ying ChengInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Wilson Wei Sheng TanInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Jerry Kok Yen ChanDepartment of Reproductive Medicine, Kandang Kerbau Women's and Children's Hospital, Singapore.
Cheng Ean CheeDepartment of Hematology-Oncology, National University Cancer Institute, Singapore.
Guan Huei LeeDivision of Gastroenterology and Hepatology, National University Health System, Singapore.
Han Chong TohDivision of Medical Oncology, National Cancer Centre Singapore, Singapore.
Seng Gee LimDivision of Gastroenterology and Hepatology, National University Health System, Singapore.ORCID 0000-0003-0994-4932
Yue WanGenome Institute of Singapore, Agency for Science, Technology and Research, Singapore.ORCID 0000-0002-2433-9637
Qingfeng ChenInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Agency for Science, Technology and Research · SGNational Cancer Centre Singapore · SGNational University Health System · SGNational University Cancer Institute, Singapore · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsRecent development of multiple treatments for human hepatocellular carcinoma (HCC) has allowed for the selection of combination therapy to enhance the effectiveness of monotherapy. Optimal selection of therapies is based on both HCC and its microenvironment. Therefore, it is critical to develop and validate preclinical animal models for testing clinical therapeutic solutions. APPROACH AND

resultsWe established cell line-based or patient-derived xenograft-based humanized-immune-system mouse models with subcutaneous and orthotopic HCC. Mice were injected with human-specific antibodies (Abs) to deplete human immune cells. We analyzed the transcription profiles of HCC cells and human immune cells by using real-time PCR and RNA sequencing. The protein level of HCC tumor cells/tissues or human immune cells was determined by using flow cytometry, western blotting, and immunohistochemistry. The HCC tumor size was measured after single, dual-combination, and triple-combination treatment using N-(1',2-Dihydroxy-1,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide (C188-9), bevacizumab, and pembrolizumab. In this study, human immune cells in the tumor microenvironment were strongly selected and modulated by HCC, which promoted the activation of the IL-6/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in tumor cells and led to augmented HCC proliferation and angiogenesis by releasing angiogenic cytokines in humanized-immune-system mice with HCC. In particular, intratumor human cluster of differentiation-positive (hCD14

conclusionsHumanized-immune-system HCC mouse models are suitable for identifying targets from cancer and immune components and for testing combinational therapies.

Indexed as

AnimalsAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBenzenesulfonamidesBevacizumabCarcinoma, HepatocellularCell Line, TumorCell ProliferationHumansInterleukin-6Janus Kinase 2Lipopolysaccharide ReceptorsLiver NeoplasmsLymphocytes, Tumor-InfiltratingMiceNaphtholsAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBenzenesulfonamidesBevacizumabC188-9 compoundInterleukin-6JAK2 protein, humanJanus Kinase 2Lipopolysaccharide ReceptorsNaphtholspembrolizumabSTAT3 protein, humanSTAT3 Transcription FactorSulfonamides

Identifiers

PMID33738839
PMCPMC9540409
OpenAlexW3136187250

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.