Evidence map›Paper›PMID 35169858›Full record

ArticleOncology reports2022

Inhibition of the VEGF signaling pathway attenuates tumor‑associated macrophage activity in liver cancer.

Shohei Okikawa, Yuji Morine, Yu Saito, Shinichiro Yamada, Kazunori Tokuda, Hiroki Teraoku, Katsuki Miyazaki, Shoko Yamashita, Tetsuya Ikemoto, Satoru Imura and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Oncology reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

35 citing papers in PubMed, 62 citations in OpenAlex.

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  15. Applications of mRNA Delivery in Cancer Immunotherapy.International journal of nanomedicine · 2025
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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 1 institution in 1 country.

Shohei OkikawaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Yuji MorineDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Yu SaitoDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Shinichiro YamadaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Kazunori TokudaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Hiroki TeraokuDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Katsuki MiyazakiDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Shoko YamashitaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Tetsuya IkemotoDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Satoru ImuraDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Mitsuo ShimadaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770‑8503, Japan.
Tokushima University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor‑associated macrophage (TAMs) are paramount for tumor progression and immune tolerance in the tumor microenvironment of various types of cancer, including liver cancer. The aim of the present study was to investigate the effect of vascular endothelial growth factor (VEGF) inhibition on TAM polarization and function during their interactions with macrophages and liver cancer cells. TAMs were induced by culturing M0 macrophages with cancer cell‑conditioned medium. TAMs cultured with cancer cell‑conditioned medium and vascular endothelial growth factor (VEGF) inhibitor were defined as modified TAMs, and the expression levels of TAM‑associated markers and VEGF receptor 2 were evaluated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The effects of TAMs and modified TAMs on cancer cell proliferation and migration were investigated using conditioned medium. Programmed death‑ligand 1 (PD‑L1) mRNA expression in modified TAMs and cancer cells cultured in modified TAM‑conditioned medium (TAM‑CM) for 48 h was examined using RT‑qPCR. In order to investigate signaling pathways in macrophages, western blot analysis was performed. CD163 and CD206 and M2 macrophage marker expression was upregulated in TAMs and modified TAMs. Modified TAM‑CM exhibited a decreased ability to promote cancer cell proliferation and migration in comparison with the use of TAM‑CM. The VEGF concentration was significantly higher in the TAMs than in M0 macrophages; however, the modified TAMs displayed a significantly lower VEGF secretion than TAMs. PD‑L1 expression was decreased in modified TAMs as compared with TAMs. Western blot analysis revealed that the Akt/mTOR signaling pathway was significantly suppressed in the modified TAMs compared with TAMs. It was observed that TAMs cultured in a VEGF‑depleted environment displayed lower secretion levels of cytokines involved in tumor progression and a decreased immune tolerance‑inducing ability. On the whole, the results of the present study suggested that VEGF inhibition in TAMs may be a potential therapeutic target for liver cancer.

Indexed as

Liver NeoplasmsVascular Endothelial Growth Factor ACell Line, TumorHumansSignal TransductionTumor-Associated MacrophagesTumor MicroenvironmentVascular Endothelial Growth Factor Aliver cancerPD‑L1tumor‑associated macrophagestumor microenvironmentVEGF

Identifiers

PMID35169858
PMCPMC8867251
OpenAlexW4211086784

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.