Evidence map›Paper›PMID 34250732›Full record

ArticleJournal of cellular and molecular medicine2021

Network analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells.

Hamid Latifi-Navid, Zahra-Soheila Soheili, Shahram Samiei, Mehdi Sadeghi, Sepideh Taghizadeh, Ehsan Ranaei Pirmardan, Hamid Ahmadieh

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Aflibercept and Faricimab Equipotently Restore Endothelial Barrier Function.Investigative ophthalmology & visual science · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Development of Biosimilar Aflibercept SDZ-AFL.Current therapeutic research, clinical and experimental · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. 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

7 authors at 4 institutions in 2 countries.

Hamid Latifi-NavidDepartment of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.ORCID 0000-0001-9418-2682
Zahra-Soheila SoheiliDepartment of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Shahram SamieiBlood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Mehdi SadeghiDepartment of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
Sepideh TaghizadehDepartment of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Ehsan Ranaei PirmardanOcular Tissue Engineering Research Center, Molecular Biomarkers Nano-Imaging Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Hamid AhmadiehOphthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
National Institute of Genetic Engineering and Biotechnology · IRBrigham and Women's Hospital · USHigh Institute for Education and Research in Transfusion Medicine · IRShahid Beheshti University of Medical Sciences · IR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Angiogenesis, inflammation and endothelial cells' migration and proliferation exert fundamental roles in different diseases. However, more studies are needed to identify key proteins and pathways involved in these processes. Aflibercept has received the approval of the US Food and Drug Administration (FDA) for the treatment of wet AMD and colorectal cancer. Moreover, the effect of Aflibercept on VEGFR2 downstream signalling pathways has not been investigated yet. Here, we integrated text mining data, protein-protein interaction networks and multi-experiment microarray data to specify candidate genes that are involved in VEGFA/VEGFR2 signalling pathways. Network analysis of candidate genes determined the importance of the nominated genes via different centrality parameters. Thereupon, several genes-with the highest centrality indexes-were recruited to investigate the impact of Aflibercept on their expression pattern in HUVEC cells. Real-time PCR was performed, and relative expression of the specific genes revealed that Aflibercept modulated angiogenic process by VEGF/PI3KA/AKT/mTOR axis, invasion by MMP14/MMP9 axis and inflammation-related angiogenesis by IL-6-STAT3 axis. Data showed Aflibercept simultaneously affected these processes and determined the nominated axes that had been affected by the drug. Furthermore, integrating the results of Aflibercept on expression of candidate genes with the current network analysis suggested that resistance against the Aflibercept effect is a plausible process in HUVEC cells.

Indexed as

HumansHuman Umbilical Vein Endothelial CellsInterleukin-6Neovascularization, PhysiologicReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsSTAT3 Transcription FactorVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2afliberceptIL6 protein, humanInterleukin-6KDR protein, humanReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsSTAT3 protein, humanSTAT3 Transcription FactorVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2VEGFA protein, humanafliberceptangiogenesisHUVEC cellsinflammationmatrix proteinsnetwork analysis

Identifiers

PMID34250732
PMCPMC8419159
OpenAlexW3180589846

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.