Evidence map›Paper›PMID 30510994›Full record

ArticleCellular and molecular gastroenterology and hepatology2019

Dipeptidyl Peptidase 4 Inhibitors Reduce Hepatocellular Carcinoma by Activating Lymphocyte Chemotaxis in Mice.

Sohji Nishina, Akira Yamauchi, Takumi Kawaguchi, Kohei Kaku, Moritaka Goto, Kyo Sasaki, Yuichi Hara, Yasuyuki Tomiyama, Futoshi Kuribayashi, Takuji Torimura and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.5field-weighted citation impact, top 5% 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

58 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
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  3. Pharmacologic DPP-4 inhibition promotes CD8bioRxiv : the preprint server for biology · 2026
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  19. Dipeptidyl peptidase 4 inhibitor reduces tumor-associated macrophages and enhances anti-PD-L1-mediated tumor suppression in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  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

11 authors at 3 institutions in 1 country.

Sohji NishinaDepartment of Hepatology and Gastroenterology, Kawasaki Medical School, Kurashiki, Japan.
Akira YamauchiDepartment of Biochemistry, Kawasaki Medical School, Kurashiki, Japan.
Takumi KawaguchiDivision of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Kohei KakuDepartment of Internal Medicine I, Kawasaki Medical School General Medical Center, Okayama, Japan.
Moritaka GotoPharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Co, Ltd, Mie, Japan.
Kyo SasakiDepartment of Hepatology and Gastroenterology, Kawasaki Medical School, Kurashiki, Japan.
Yuichi HaraDepartment of Hepatology and Gastroenterology, Kawasaki Medical School, Kurashiki, Japan.
Yasuyuki TomiyamaDepartment of Hepatology and Gastroenterology, Kawasaki Medical School, Kurashiki, Japan.
Futoshi KuribayashiDepartment of Biochemistry, Kawasaki Medical School, Kurashiki, Japan.
Takuji TorimuraDivision of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Keisuke HinoDepartment of Hepatology and Gastroenterology, Kawasaki Medical School, Kurashiki, Japan. Electronic address: khino@med.kawasaki-m.ac.jp.
Kawasaki Medical School · JPKurume University · JPRiso Kagaku (Japan) · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & Aims: CD26, a multifunctional transmembrane glycoprotein, is expressed in various cancers and functions as dipeptidyl peptidase 4 (DPP4). We investigated whether CD26 expression is associated with hepatocellular carcinoma (HCC) progression and whether DPP4 inhibitors exert antitumor effects against HCC. Methods: CD26 expression was examined in 41 surgically resected HCC specimens. The effects of DPP4 inhibitors on HCC were examined by using HCC cell lines (Huh-7 and Li-7), xenograft tumors in nude mice, and a nonalcoholic steatohepatitis-related HCC mouse model. Results: CD26 expression in HCC specimens was associated with increased serum DPP4 activity, as well as a more advanced stage, less tumor immunity, and poorer prognosis in HCC patients. The HCC cell lines and xenograft tumors exhibited CD26 expression and DPP4 activity. The DPP4 inhibitors did not exhibit antitumor effects in vitro, but natural killer (NK) and/or T-cell tumor accumulation suppressed growth of xenograft tumor and HCC in vivo. The antitumor effects of DPP4 inhibitors were abolished by the depletion of NK cells or the neutralization of CXCR3, a chemokine receptor on NK cells. EZ-TAXIScan, an optical horizontal chemotaxis apparatus, identified enhanced NK and T-cell chemotaxis by DPP4 inhibitors ex vivo in the presence of Huh-7 cells and the chemokine CXCL10, which binds to CXCR3. The DPP4 inhibitors prevented the biologically active form of CXCL10 from being truncated by Huh-7 cell DPP4 activity. DPP4 inhibitors also suppressed tumor angiogenesis. Conclusions: These results provide a rationale for verifying whether DPP4 inhibitors clinically inhibit the progression of HCC or augment the antitumor effects of molecular-targeting drugs or immunotherapies against HCC.

Indexed as

ChemotaxisAgedAnimalsAntineoplastic AgentsCarcinoma, HepatocellularCell CycleCell Line, TumorChemokine CXCL10Dipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsFemaleHumansKiller Cells, NaturalLiver NeoplasmsLymphocytes, Tumor-InfiltratingMaleanagliptinAntineoplastic AgentsChemokine CXCL10Dipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsPyrimidinesSitagliptin PhosphateVildagliptinanti-ASGM, anti-asialo GM1 antiseraCCK-8, Cell Counting Kit 8CD26CXCL10DM, diabetes mellitusDPP4, dipeptidyl peptidase 4FBS, fetal bovine serumHCC, hepatocellular carcinomaHCV, hepatitis C virusHPLC, high-performance liquid chromatographyIC50, inhibitory concentration of 50%Ig, immunoglobulinLDH, lactate dehydrogenaseMICA, MHC class I polypeptide-related sequence ANAFLD, nonalcoholic fatty liver diseaseNASH, nonalcoholic steatohepatitisNK CellNK, natural killerPBMC, peripheral blood mononuclear cellPBS, phosphate-buffered salinePTH, phenylthiohydantoinSDS-PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresisTAXIScanT CellTumor Immunity

Identifiers

PMID30510994
PMCPMC6260362
OpenAlexW2891247326

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.