ArticlePloS one2016
Anti-Tumor Effects of Second Generation β-Hydroxylase Inhibitors on Cholangiocarcinoma Development and Progression.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- Overexpression and prognostic value of aspartate β-hydroxylase in lung adenocarcinoma: a comprehensive study based on bioinformatics and clinical tissue sample validation.World journal of surgical oncology · 2026Article
- Article
- Chondrosarcoma: Adjuvant Therapeutic Effects of the ASPH Small Molecule Inhibitor, SMI-1182, With Doxorubicin.Japanese journal of cancer and oncology research · 2025Article
- Multi-omics integration identifies ASPH and PTTG1 as potential causal drivers of lung adenocarcinoma progression and immune evasion.Frontiers in immunology · 2025Article
- Inhibition of Aspartate β-Hydroxylase Enhances Anti-Tumor Immunity.ImmunoTargets and therapy · 2025Article
- Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models.International journal of molecular sciences · 2024Article
- Elevated 2-oxoglutarate antagonizes DNA damage responses in cholangiocarcinoma chemotherapy through regulating aspartate beta-hydroxylase.Cancer letters · 2024Article
- Aspartate β-hydroxylase Regulates Expression ofJournal of Cancer · 2024Article
- Heterogeneous Response of Tumor Cell Lines to Inhibition of Aspartate β-hydroxylase.Journal of Cancer · 2024Article
- Molecular profiling reveals potential targets in cholangiocarcinoma.World journal of gastroenterology · 2023Article
- Atractylodin and β-eudesmol from Atractylodes lancea (Thunb.) DC. Inhibit Cholangiocarcinoma Cell Proliferation by Downregulating the Notch Signaling Pathway.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Development and Characterization of Human Primary Cholangiocarcinoma Cell Lines.The American journal of pathology · 2022Review
- Dietary Soy Prevents Alcohol-Mediated Neurocognitive Dysfunction and Associated Impairments in Brain Insulin Pathway Signaling in an Adolescent Rat Model.Biomolecules · 2022Article
- Notch signaling in the pathogenesis, progression and identification of potential targets for cholangiocarcinoma (Review).Molecular and clinical oncology · 2022Review
- Targeting Aspartate Beta-Hydroxylase with the Small Molecule Inhibitor MO-I-1182 Suppresses Cholangiocarcinoma Metastasis.Digestive diseases and sciences · 2021Article
- Multi-organ metastasis as destination for breast cancer cells guided by biomechanical architecture.American journal of cancer research · 2021Article
- Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target.Frontiers in oncology · 2021Article
- Diverse molecular functions of aspartate β‑hydroxylase in cancer (Review).Oncology reports · 2020Review
- Small-molecule active pharmaceutical ingredients of approved cancer therapeutics inhibit human aspartate/asparagine-β-hydroxylase.Bioorganic & medicinal chemistry · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Cholangiocarcinoma (CCA) has a poor prognosis due to widespread intrahepatic spread. Aspartate β-hydroxylase (ASPH) is a transmembrane protein and catalyzes the hydroxylation of aspartyl and asparaginyl residues in calcium binding epidermal growth factor (cbEGF)-like domains of various proteins, including Notch receptors and ligands. ASPH is highly overexpressed (>95%) in human CCA tumors. We explored the molecular mechanisms by which ASPH mediated the CCA malignant phenotype and evaluated the potential of ASPH as a therapeutic target for CCA. The importance of expression and enzymatic activity of ASPH for CCA growth and progression was examined using shRNA "knockdown" and a mutant construct that reduced its catalytic activity. Second generation small molecule inhibitors (SMIs) of β-hydroxylase activity were developed and used to target ASPH in vitro and in vivo. Subcutaneous and intrahepatic xenograft rodent models were employed to determine anti-tumor effects on CCA growth and development. It was found that the enzymatic activity of ASPH was critical for mediating CCA progression, as well as inhibiting apoptosis. Mechanistically, ASPH overexpression promoted Notch activation and modulated CCA progression through a Notch1-dependent cyclin D1 pathway. Targeting ASPH with shRNAs or a SMI significantly suppressed CCA growth in vivo.
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Registered trials
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