ArticleScientific reports2018
Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- DHODH-Mediated Suppression of Ferroptosis Supports Radioresistance and Represents a Therapeutic Vulnerability in Lung Cancer.Cancer research · 2026Article
- A CCL5Cell & bioscience · 2025Article
- Synovial mesenchymal stem cell-derived exosomes delivering GRPEL1 activate PINK1-mediated mitophagy to promote cartilage repair in arthritis.World journal of stem cells · 2025Article
- Anticancer effect of the antirheumatic drug leflunomide on oral squamous cell carcinoma by the inhibition of tumor angiogenesis.Discover oncology · 2025Article
- Premature renal epithelial cell senescence promoted by LXN/Rps3/p53 signaling pathway activation increases calcium oxalate crystal deposition by altering macrophage polarization.Frontiers in immunology · 2025Article
- An endothelial-related prognostic index for bladder cancer patients.Discover oncology · 2024Article
- Targeting EFNA1 suppresses tumor progression via the cMYC-modulated cell cycle and autophagy in esophageal squamous cell carcinoma.Discover oncology · 2023Article
- EphrinA3 is a key regulator of malignant behaviors and a potential prognostic factor in lung adenocarcinoma.Cancer medicine · 2023Article
- Geometric Control of Cell Behavior by Biomolecule Nanodistribution.ACS biomaterials science & engineering · 2022Article
- The dynamic roles of the bladder tumour microenvironment.Nature reviews. Urology · 2022Review
- Review
- Potential predictive and therapeutic applications of small extracellular vesicles-derived circPARD3B in osteoarthritis.Frontiers in pharmacology · 2022Article
- Eph Receptors and Ephrins in Retinal Diseases.International journal of molecular sciences · 2021Review
- Cardiovascular effects of approved drugs for rheumatoid arthritis.Nature reviews. Rheumatology · 2021Review
- The Role of Eph Receptors and Ephrins in Corneal Physiology and Diseases.International journal of molecular sciences · 2021Review
- Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review.International immunopharmacology · 2021Review
- AhR and Cancer: From Gene Profiling to Targeted Therapy.International journal of molecular sciences · 2021Review
- Angiogenesis is Inhibited by Arsenic Trioxide Through Downregulation of the CircHIPK3/miR-149-5p/FOXO1/VEGF Functional Module in Rheumatoid Arthritis.Frontiers in pharmacology · 2021Article
- Therapeutic Potential of Exosomal circRNA Derived from Synovial Mesenchymal Cells via Targeting circEDIL3/miR-485-3p/PIAS3/STAT3/VEGF Functional Module in Rheumatoid Arthritis.International journal of nanomedicine · 2021Article
- α-Mangostin Alleviated HIF-1α-Mediated Angiogenesis in Rats With Adjuvant-Induced Arthritis by Suppressing Aerobic Glycolysis.Frontiers in pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis plays an important role in bladder cancer (BCa). The immunosuppressive drug leflunomide has attracted worldwide attention. However, the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a monomeric protein that is a functional form of the ligand. The co-culture supernatants containing sEphrin-A1 caused the internalization and down-regulation of EphA2 on endothelial cells and dramatic functional activation of HUVECs. This sEphrin-A1/EphA2 system is mainly functional in regulating angiogenesis in BCa tissue. We showed that leflunomide (LEF) inhibited angiogenesis in a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder carcinogenesis model and a tumor xenograft model, as well as in BCa cell and HUVEC co-culture systems, via significant inhibition of the sEphrin-A1/EphA2 system. Ephrin-A1 overexpression could partially reverse LEF-induced suppression of angiogenesis and subsequent tumor growth inhibition. Thus, LEF has a significant anti-angiogenesis effect on BCa cells and BCa tissue via its inhibition of the functional angiogenic sEphrin-A1/EphA2 system and may have potential for treating BCa beyond immunosuppressive therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.