Evidence map›Paper›PMID 32683508›Full record

ArticleCancer immunology, immunotherapy : CII2021

Leukotriene receptor antagonists enhance HCC treatment efficacy by inhibiting ADAMs and suppressing MICA shedding.

Jun Arai, Kaku Goto, Yumi Otoyama, Yoko Nakajima, Ikuya Sugiura, Atsushi Kajiwara, Masayuki Tojo, Yuki Ichikawa, Shojiro Uozumi, Yuu Shimozuma and 7 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  10. Targeting inflammation as cancer therapy.Journal of hematology & oncology · 2024
    Review
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  13. Article
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  16. Cysteinyl Leukotriene Pathway and Cancer.International journal of molecular sciences · 2021
    Review
  17. 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 3 institutions in 1 country.

Jun AraiDivision of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. araiguma10@med.showa-u.ac.jp.ORCID http://orcid.org/0000-0002-3810-8784
Kaku GotoDivision of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yumi OtoyamaDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Yoko NakajimaDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Ikuya SugiuraDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Atsushi KajiwaraDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Masayuki TojoDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Yuki IchikawaDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Shojiro UozumiDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Yuu ShimozumaDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Manabu UchikoshiDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Masashi SakakiDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Hisako NozawaDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Ryo NakagawaDivision of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Ryosuke MuroyamaDivision of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Naoya KatoDivision of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hitoshi YoshidaDivision of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Showa University · JPChiba University · JPThe University of Tokyo · JP

Funding

Japan Agency for Medical Research and Development 15fk0310009h0004Japan Agency for Medical Research and Development 19fk0210052s0201Ministry of Education, Culture, Sports, Science and Technology (JP) 19K16723Ministry of Education, Culture, Sports, Science and Technology (JP) 24390184
6 · The paper itself

Abstract

In our previous genome-wide association study, we demonstrated the association between MHC class I-related chain A (MICA) and hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C. Increasing membrane-bound MICA (mMICA) in cancer cells by reducing MICA sheddases facilitates natural killer (NK) cell-mediated cytotoxicity. Our recent study clarified that A disintegrin and metalloproteases (ADAM), including ADAM9, are MICA sheddases in HCC, and that the suppression of ADAMs increases mMICA, demonstrating the rationality of mMICA-NK targeted therapy. Furthermore, we showed that regorafenib suppresses ADAM9 transcriptionally and translationally. A library of FDA-approved drugs was screened for more efficient inhibitors of ADAM9. Flow cytometry evaluation of the expression of mMICA after treatment with various candidate drugs identified leukotriene receptor antagonists as potential ADAM9 inhibitors. Furthermore, leukotriene receptor antagonists alone or in combination with regorafenib upregulated mMICA, which was in turn downregulated by leukotriene C4 and D4 via ADAM9 function. Our study demonstrates that leukotriene receptor antagonists could be developed as novel drugs for immunological control and suppression of ADAM9 in HCC. Further, leukotriene receptor antagonists should be explored as combination therapy partners with conventional multi-kinase inhibitors for developing therapeutic strategies with enhanced efficacies for HCC management and treatment.

Indexed as

ADAM ProteinsCarcinoma, HepatocellularCell Line, TumorDown-RegulationGene Expression Regulation, NeoplasticGenome-Wide Association StudyHep G2 CellsHistocompatibility Antigens Class IHumansKiller Cells, NaturalLeukotriene AntagonistsLiver NeoplasmsMembrane ProteinsPhenylurea CompoundsPyridinesTreatment OutcomeADAM ProteinsHistocompatibility Antigens Class ILeukotriene AntagonistsMembrane ProteinsMHC class I-related chain APhenylurea CompoundsPyridinesregorafenibA disintegrin and metalloprotease 9Hepatocellular carcinomaLeukotriene D4MHC class I-related chain ARegorafenib

Identifiers

PMID32683508
PMCPMC7838147
OpenAlexW3043569505

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.