ArticleNitric oxide : biology and chemistry2017
Nitric oxide-mediated resistance to photodynamic therapy in a human breast tumor xenograft model: Improved outcome with NOS2 inhibitors.
Article in Nitric oxide : biology and chemistry, 2017. 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 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
- Photodynamic treatment of glioblastoma plus endothelial cell spheroid models: increased proliferative and migratory aggressiveness of surviving tumor cells due to iNOS/NO upregulation.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- S-nitrosylated COX-2 is a microenvironment-regulated breast cancer cell biomarker of mesenchymal phenotypes.Experimental cell research · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Pro-tumor effects of nitric oxide from stress-upregulated inducible nitric oxide synthase in anti-tumor photodynamic therapy.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025Review
- The Role of Nitric Oxide in Cancer Treatment: Ally or Foe?Molecules (Basel, Switzerland) · 2025Review
- Production and Role of Nitric Oxide in Endometrial Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Participation of lipids in the tumor response to photodynamic therapy and its exploitation for therapeutic gain.Journal of lipid research · 2025Review
- Photosensitized Oxidative Damage from a New Perspective: The Influence of Before-Light and After-Light Reaction Conditions.The Journal of organic chemistry · 2024Review
- Molecular Determinants for Photodynamic Therapy Resistance and Improved Photosensitizer Delivery in Glioma.International journal of molecular sciences · 2024Review
- Upregulation of iNOS/NO in Cancer Cells That Survive a Photodynamic Challenge: Role of No in Accelerated Cell Migration and Invasion.International journal of molecular sciences · 2024Review
- Endoplasmic reticulum stress and expression of nitric oxide synthases in heart failure with preserved and with reduced ejection fraction - pilot study.Cardiology journal · 2024Article
- Pro-Tumor Activity of Endogenous Nitric Oxide in Anti-Tumor Photodynamic Therapy: Recently Recognized Bystander Effects.International journal of molecular sciences · 2023Review
- Understanding the Photodynamic Therapy Induced Bystander and Abscopal Effects: A Review.Antioxidants (Basel, Switzerland) · 2023Review
- Ferroptosis regulator NOS2 is closely associated with the prognosis and cell malignant behaviors of hepatoblastoma: a bioinformatic andFrontiers in oncology · 2023Article
- Adjuvant Photodynamic Therapy, Mediated via Topical Versus Systemic Administration of 5-Aminolevulinic Acid for Control of Murine Mammary Tumor after Surgical Resection.Photochemistry and photobiology · 2022Article
- The Negative Impact of Cancer Cell Nitric Oxide on Photodynamic Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy.Pharmaceutics · 2021Review
- Photodynamic Therapy as an Oxidative Anti-Tumor Modality: Negative Effects of Nitric Oxide on Treatment Efficacy.Pharmaceutics · 2021Review
- Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy.Pharmaceuticals (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Many malignant tumors employ iNOS-derived NO to resist eradication by chemotherapeutic agents or ionizing radiation. In this study, we determined whether human breast carcinoma MDA-MB-231 cells in vitro and in vivo as tumor xenografts would exploit endogenous iNOS/NO to resist the cytotoxic effects of 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT). Broad band visible irradiation of ALA-treated cells resulted in a marked after-light upregulation of iNOS protein which persisted for at least 24 h. Apoptotic killing of ALA/light-challenged cells was significantly enhanced by iNOS inhibitors (1400W, GW274150) and a NO trap (cPTIO), implying that stress-induced iNOS/NO was acting cytoprotectively. We found that cells surviving the photostress proliferated and migrated more rapidly than controls in 1400W- and cPTIO-inhibitable fashion, indicating iNOS/NO involvement. Female SCID mice bearing MDA-MB-231 tumors were used for animal model experiments. ALA-PDT with a 633 nm light source caused a significant reduction in post-irradiation tumor growth relative to light-only controls, which was further reduced by administration of 1400W or GW274150, whereas 1400W had little or no effect on controls. Immunoblot analyses of tumor samples revealed a progressive post-PDT upregulation of iNOS, which reached >5-times the control level after six days. Correspondingly, the nitrite/nitrate level in post-PDT tumor samples was substantially higher than that in controls. In addition, a 1400W-inhibitable upregulation of pro-survival/progression effector proteins such as Bcl-xL, Survivin, and S100A4 was observed after in vitro and in vivo ALA-PDT. This is the first known study to demonstrate iNOS/NO-induced resistance to PDT in an in vivo human tumor model.
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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.