Evidence map›Paper›PMID 38180972›Full record

ArticleHepatology communications2024

Nucleos(t)ide analogs for hepatitis B virus infection differentially regulate the growth factor signaling in hepatocytes.

Ryogo Shimizu, Kazuhisa Murai, Kensuke Tanaka, Yuga Sato, Naho Takeda, Saki Nakasyo, Takayoshi Shirasaki, Kazunori Kawaguchi, Tetsuro Shimakami, Kouki Nio and 8 more

Open access · goldAbstract read
In one paragraph

Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

18 authors at 4 institutions in 1 country.

Ryogo ShimizuDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Kazuhisa MuraiDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Kensuke TanakaDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Yuga SatoDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Naho TakedaDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Saki NakasyoDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Takayoshi ShirasakiDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Kazunori KawaguchiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Tetsuro ShimakamiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Kouki NioDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Yuki NakayaDepartment of Infection and Immunity, Division of Virology, Jichi Medical University, Shimotsuke, Japan.
Harumi KagiwadaBiological Data Science Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
Katsuhisa HorimotoArtificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
Masashi MizokamiGenome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan.
Shuichi KanekoDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Kazumoto MurataDepartment of Infection and Immunity, Division of Virology, Jichi Medical University, Shimotsuke, Japan.
Taro YamashitaDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Masao HondaDepartment of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.ORCID 0000-0003-3050-5854
Kanazawa University · JPJichi Medical University · JPNational Institute of Advanced Industrial Science and Technology · JPNational Center for Global Health and Medicine · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecent clinical studies have suggested that the risk of developing HCC might be lower in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate than in patients receiving entecavir, although there is no difference in biochemical and virological remission between the 2 drugs.

methodsThe effects of nucleoside analogs (NsAs; lamivudine and entecavir) or nucleotide analogs (NtAs; adefovir disoproxil, tenofovir disoproxil fumarate, and tenofovir alafenamide) on cell growth and the expression of growth signaling molecules in hepatoma cell lines and PXB cells were investigated in vitro. The tumor inhibitory effects of NsAs or NtAs were evaluated using a mouse xenograft model, and protein phosphorylation profiles were investigated. The binding of NsAs or NtAs to the insulin receptor (INSR) was investigated by thermal shift assays.

resultsNtAs, but not NsAs, showed direct growth inhibitory effects on hepatoma cell lines in vitro and a mouse model in vivo. A phosphoprotein array revealed that INSR signaling was impaired and the levels of phosphorylated (p)-INSRβ and downstream molecules phosphorylated (p)-IRS1, p-AKT, p-Gab1, and p-SHP2 were substantially reduced by NtAs. In addition, p-epidermal growth factor receptor and p-AKT levels were substantially reduced by NtAs. Similar findings were also found in PXB cells and nontumor lesions of liver tissues from patients with chronic hepatitis B. Prodrug NtAs, but not their metabolites (adefovir, adefovir monophosphate, adefovir diphosphate, tenofovir, tenofovir monophosphate, and tenofovir diphosphate), had such effects. A thermal shift assay showed the binding of NtAs to INSRβ.

conclusionsNtAs (adefovir disoproxil, tenofovir disoproxil fumarate, and tenofovir alafenamide), which are adenine derivative acyclic nucleotide analogs, potentially bind to the ATP-binding site of growth factor receptors and inhibit their autophosphorylation, which might reduce the risk of HCC in patients with chronic hepatitis B.

Indexed as

Carcinoma, HepatocellularHepatitis BHepatitis B, ChronicLiver NeoplasmsAdenineHepatitis B virusHepatocytesHumansIntercellular Signaling Peptides and ProteinsNucleotidesOrganophosphonatesProto-Oncogene Proteins c-aktTenofoviradefovirAdenineIntercellular Signaling Peptides and ProteinsNucleotidesOrganophosphonatesProto-Oncogene Proteins c-aktTenofovir

Identifiers

PMID38180972
PMCPMC10781114
OpenAlexW4390604330

What OpenQuestion holds

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LicenceCC BY
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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.