ArticleOncotarget2016
Inducible nitric oxide synthase enhances disease aggressiveness in pancreatic cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Prognostic Value of Inducible Nitric Oxide Synthase (iNOS) in Human Cancer: A Systematic Review and Meta-Analysis.BioMed research international · 2019Pooled it
- Unraveling the Biology of Interferon-Stimulated Genes: Mechanisms, Functions, and Clinical Implications.Infection and drug resistance · 2026Review
- Gasotransmitters bridging tumor biology and immunity: from pathophysiological insights to therapeutic potential.Frontiers in immunology · 2026Review
- NO/iNOS axis impact on glioma stem cells and temozolomide resistance.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Nitric oxide‑mediated S‑Nitrosylation contributes to signaling transduction in human physiological and pathological status (Review).International journal of molecular medicine · 2025Review
- Innate Immunity and Platelets: Unveiling Their Role in Chronic Pancreatitis and Pancreatic Cancer.Cancers · 2025Review
- NO: a key player in microbiome dynamics and cancer pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- Imaging Techniques and Biochemical Biomarkers: New Insights into Diagnosis of Pancreatic Cancer.Cell biochemistry and biophysics · 2024Review
- The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer.Frontiers in physiology · 2024Review
- Evaluating Metabolite-Based Biomarkers for Early Diagnosis of Pancreatic Cancer: A Systematic Review.Metabolites · 2023Review
- Chronic Exposure to Nitric Oxide Induces P53 Mutations and Malignant-like Features in Human Breast Epithelial Cells.Biomolecules · 2023Article
- Article
- The Role of Heme Peroxo Oxidants in the Rational Mechanistic Modeling of Nitric Oxide Synthase: Characterization of Key Intermediates and Elucidation of the Mechanism.Angewandte Chemie (International ed. in English) · 2022Article
- Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review).Molecular medicine reports · 2022Review
- NOS2 andProceedings of the National Academy of Sciences of the United States of America · 2022Article
- A Prognostic Survival Model of Pancreatic Adenocarcinoma Based on Metabolism-Related Gene Expression.Frontiers in genetics · 2022Article
- Protein Phosphorylation in Cancer: Role of Nitric Oxide Signaling Pathway.Biomolecules · 2021Review
- Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs.International journal of molecular sciences · 2021Review
- Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.Frontiers in pharmacology · 2021Review
- Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway.Nature communications · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic cancer is one of the most lethal malignancies and is refractory to the available treatments. Pancreatic ductal adenocarcinoma (PDAC) expresses high level of inducible nitric oxide synthase (NOS2), which causes sustained production of nitric oxide (NO). We tested the hypothesis that an aberrantly increased NO-release enhances the development and progression of PDAC. Enhanced NOS2 expression in tumors significantly associated with poor survival in PDAC patients (N = 107) with validation in independent cohorts. We then genetically targeted NOS2 in an autochthonous mouse model of PDAC to examine the effect of NOS2-deficiency on disease progression and survival. Genetic ablation of NOS2 significantly prolonged survival and reduced tumor severity in LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mice. Primary tumor cells isolated from NOS2-deficient KPC (NKPC) mice showed decreased proliferation and invasiveness as compared to those from KPC mice. Furthermore, NKPC tumors showed reduced expression of pERK, a diminished inactivation of Forkhead box transcription factor O (FOXO3), a tumor suppressor, and a decrease in the expression of oncomir-21, when compared with tumors in KPC mice. Taken together, these findings showed that NOS2 is a predictor of prognosis in early stage, resected PDAC patients, and provide proof-of-principle that targeting NOS2 may have potential therapeutic value in this lethal malignancy.
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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.