ArticleAngiogenesis2017
A new key player in VEGF-dependent angiogenesis in human hepatocellular carcinoma: dimethylarginine dimethylaminohydrolase 1.
Article in Angiogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 70 citations in OpenAlex.
- DDAH1 Promotes Cisplatin Chemoresistance in Patients with Locally Advanced Nasopharyngeal Carcinoma via the EGFR-JAK2-STAT3 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Dual Role of Nitric Oxide in Allergic Rhinitis: From the NO/cGMP Signaling Pathway to Possible New Therapeutic Targets for Organelle Damage.Journal of inflammation research · 2025Review
- Unraveling the role of PBK in glioblastoma: from molecular mechanisms to therapeutic targets.Annals of medicine and surgery (2012) · 2024Article
- The correlation of ADMA with proinflammatory, liver injury and cancer biomarkers in patients with liver dysfunction.Hepatology forum · 2024Article
- Development of a HPLC-MS/MS Method to Assess the Pharmacokinetics and Tumour Distribution of the Dimethylarginine Dimethylaminohydrolase 1 Inhibitors ZST316 and L-257 in a Xenograft Model of Triple-Negative Breast Cancer in Mice.Molecules (Basel, Switzerland) · 2023Article
- Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria.Blood advances · 2021Article
- Effect of Hyperbaric Oxygenation on Blood Cytokines and Arginine Derivatives; No Evidence for Induction of Inflammation or Endothelial Injury.Journal of clinical medicine · 2021Article
- Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1.iScience · 2021Article
- Apatinib suppresses the migration, invasion and angiogenesis of hepatocellular carcinoma cells by blocking VEGF and PI3K/AKT signaling pathways.Molecular medicine reports · 2021Article
- Diazoxide Post-conditioning Activates the HIF-1/HRE Pathway to Induce Myocardial Protection in Hypoxic/Reoxygenated Cardiomyocytes.Frontiers in cardiovascular medicine · 2021Article
- ADMA (asymmetric dimethylarginine) and angiogenic potential in patients with type 2 diabetes and prediabetes.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Dynamic Changes of Urine Proteome in Rat Models Inoculated with Two Different Hepatoma Cell Lines.Journal of oncology · 2021Article
- NO and hepatocellular cancer.British journal of pharmacology · 2020Review
- Esophageal Squamous Cell Carcinoma Is Accompanied by Local and Systemic Changes in L-arginine/NO Pathway.International journal of molecular sciences · 2020Article
- RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K/AKT signaling.Oncology letters · 2020Article
- Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings.International journal of molecular sciences · 2020Article
- Effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9, VEGF, anti-proliferatory cytotoxic and apoptotic properties.Molecular biology reports · 2020Article
- Anti-inflammatory and anti-angiogenesis effect of bee pollen methanolic extract using air pouch model of inflammation.Research in pharmaceutical sciences · 2020Article
- The suppressing effects of VEGF-mediated angiogenesis at different administration sequences of apatinib and transarterial embolizationTranslational cancer research · 2020Article
- Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy.Journal of Cancer · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnti-angiogenic therapies, targeting VEGF, are a promising treatment for hepatocellular carcinoma (HCC). To enhance this potential therapy, identification of novel targets in this pathway is of major interest. Nitric oxide (NO) plays a crucial role in VEGF-dependent angiogenesis. NO production depends on arginine as substrate and asymmetric dimethylarginine (ADMA) as inhibitor. Dimethylarginine dimethylaminohydrolase 1 (DDAH-1) catabolizes ADMA and therefore regulates NO and VEGF expression. This study unravels additional mechanisms to improve VEGF targeting therapies.
methodsThe expression of DDAH-1 was examined in HCC specimen and non-tumorous background liver of 20 patients undergoing liver resection. Subsequently, arginine/ADMA balance, NO production, and VEGF expression were analyzed. The influence of hypoxia on DDAH-1 and angiogenesis promoting factors was evaluated in HepG2 cells and primary human hepatocytes.
resultsDDAH-1 expression was significantly induced in primary HCC tumors compared to non-tumorous background liver. This was associated with an increased arginine/ADMA ratio, higher NO formation, and higher VEGF expression in human HCC compared to non-tumorous liver. Hypoxia induced DDAH-1, iNOS, and VEGF expression in a time-dependent manner in HepG2 cells.
conclusionsOur results indicate that DDAH-1 expression is increased in human HCC, which is associated with an increase in the arginine/ADMA ratio and enhanced NO formation. Hypoxia may be an initiating factor for the increase in DDAH-1 expression. DDAH-1 expression is associated with promotion of angiogenesis stimulating factor VEGF. Together, our findings for the first time identified DDAH-1 as a key player in the regulation of angiogenesis in human HCC, and by understanding this mechanism, future therapeutic strategies targeting VEGF can be improved.
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