ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Targeted inhibition of inducible nitric oxide synthase inhibits growth of human melanoma in vivo and synergizes with chemotherapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 120 citations in OpenAlex.
- Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy.Frontiers in immunology · 2020Trial
- S-nitrosylation of IRF7 induced by NOS1 expression in melanoma suppresses anti-tumor immunity.Cell death & disease · 2026Article
- NO/iNOS axis impact on glioma stem cells and temozolomide resistance.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Characterizing spatial immune architecture in metastatic melanoma using high-dimensional multiplex imaging.Frontiers in immunology · 2025Article
- Development of a human colorectal carcinoma cell-based platform for studying inducible nitric oxide synthase expression and nitric oxide signaling dynamics.Frontiers in molecular biosciences · 2025Article
- Nitric Oxide Signaling and Sensing in Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- In Vitro Cytotoxic Potential and In Vivo Antitumor Effects of NOS/PDK-Inhibitor T1084.International journal of molecular sciences · 2024Article
- NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer.International journal of molecular sciences · 2024Review
- Stigmasterol Exerts an Anti-Melanoma Property through Down-Regulation of Reactive Oxygen Species and Programmed Cell Death Ligand 1 in Melanoma Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Innovations in Molecular Biomarkers and Biomaterial-Based Immunotherapies for Head & Neck Cancer.Current surgery reports · 2024Review
- Development of a Macrophage-Related Risk Model for Metastatic Melanoma.International journal of molecular sciences · 2023Article
- The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023Review
- Inducible nitric oxide synthase (iNOS)-activated Cxcr2 signaling in myeloid cells promotes TGFβ-dependent squamous cell carcinoma lung metastasis.Cancer letters · 2023Article
- Targeting Nitric Oxide: Say NO to Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Redox-Related Proteins in Melanoma Progression.Antioxidants (Basel, Switzerland) · 2022Article
- Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies.Antioxidants (Basel, Switzerland) · 2021Review
- Cytotoxicity of synthetic derivatives against breast cancer and multi-drug resistant breast cancer cell lines: a literature-based perspective study.Cancer cell international · 2021Review
- Review
- Micromonospora species from rarely-exploited Egyptian habitats: chemical profile, antimicrobial, and antitumor activities through antioxidant property.Applied microbiology and biotechnology · 2021Article
- Biomaterial-Facilitated Immunotherapy for Established Oral Cancers.ACS biomaterials science & engineering · 2021Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeAberrant expression of inflammatory molecules, such as inducible nitric oxide (NO) synthase (iNOS), has been linked to cancer, suggesting that their inhibition is a rational therapeutic approach. Whereas iNOS expression in melanoma and other cancers is associated with poor clinical prognosis, in vitro and in vivo studies suggest that iNOS and NO can have both protumor and antitumor effects. We tested the hypothesis that targeted iNOS inhibition would interfere with human melanoma growth and survival in vivo in a preclinical model. EXPERIMENTAL
designWe used an immunodeficient non-obese diabetic/severe combined immunodeficient xenograft model to test the susceptibility of two different human melanoma lines to the orally-given iNOS-selective small molecule antagonist N(6)-(1-iminoethyl)-l-lysine-dihydrochloride (L-nil) with and without cytotoxic cisplatin chemotherapy.
resultsL-nil significantly inhibited melanoma growth and extended the survival of tumor-bearing mice. L-nil treatment decreased the density of CD31+ microvessels and increased the number of apoptotic cells in tumor xenografts. Proteomic analysis of melanoma xenografts with reverse-phase protein array identified alterations in the expression of multiple cell signaling and survival genes after L-nil treatment. The canonical antiapoptotic protein Bcl-2 was downregulated in vivo and in vitro after L-nil treatment, which was associated with increased susceptibility to cisplatin-mediated tumor death. Consistent with this observation, combination therapy with L-nil plus cisplatin in vivo was more effective than either drug alone, without increased toxicity.
conclusionsThese data support the hypothesis that iNOS and iNOS-derived NO support tumor growth in vivo and provide convincing preclinical validation of targeted iNOS inhibition as therapy for solid tumors.
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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.