ArticleJournal of translational medicine2008
NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols.
Article in Journal of translational medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- GTN Enhances Antitumor Effects of Doxorubicin in TNBC by Targeting the Immunosuppressive Activity of PMN-MDSC.Cancers · 2023Article
- Article
- Opportunities for Nitric Oxide in Potentiating Cancer Immunotherapy.Pharmacological reviews · 2022Review
- Molecular Mechanisms of Cytotoxicity of NCX4040, the Non-Steroidal Anti-Inflammatory NO-Donor, in Human Ovarian Cancer Cells.International journal of molecular sciences · 2022Article
- Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review).Molecular medicine reports · 2022Review
- Article
- Role of Oxygen and Nitrogen Radicals in the Mechanism of Anticancer Drug Cytotoxicity.Journal of cancer science & therapy · 2020Article
- Pharmacological manipulation of cGMP and NO/cGMP in CNS drug discovery.Nitric oxide : biology and chemistry · 2019Review
- In Vivo Molecular Electron Paramagnetic Resonance-Based Spectroscopy and Imaging of Tumor Microenvironment and Redox Using Functional Paramagnetic Probes.Antioxidants & redox signaling · 2018Review
- Prodrugs Bioactivated to Quinones Target NF-κB and Multiple Protein Networks: Identification of the Quinonome.Chemical research in toxicology · 2016Article
- Nitric oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective.Journal of cancer science & therapy · 2016Article
- Extending the translational potential of targeting NO/cGMP-regulated pathways in the CVS.British journal of pharmacology · 2015Review
- Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.PloS one · 2014Article
- Quinone-induced activation of Keap1/Nrf2 signaling by aspirin prodrugs masquerading as nitric oxide.Chemical research in toxicology · 2012Article
- Multi-arm polymeric nanocarrier as a nitric oxide delivery platform for chemotherapy of head and neck squamous cell carcinoma.Biomaterials · 2012Article
- Nitroxides as cancer imaging agents.Anti-cancer agents in medicinal chemistry · 2011Review
- GT-094, a NO-NSAID, inhibits colon cancer cell growth by activation of a reactive oxygen species-microRNA-27a: ZBTB10-specificity protein pathway.Molecular cancer research : MCR · 2011Article
- Hypoxia induces chemoresistance in ovarian cancer cells by activation of signal transducer and activator of transcription 3.International journal of cancer · 2009Article
- In vivo EPR measurement of glutathione in tumor-bearing mice using improved disulfide biradical probe.Free radical biology & medicine · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOvarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied.
methodsNCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice. Electron paramagnetic resonance (EPR) was used for measurements of nitric oxide and redox state. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies.
resultsCells treated with NCX-4040 (25 microM) showed a significant reduction of cell viability (A2780 WT, 34.9 +/- 8.7%; A2780 cDDP, 41.7 +/- 7.6%; p < 0.05). Further, NCX-4040 significantly enhanced the sensitivity of A2780 cDDP cells (cisplatin alone, 80.6 +/- 11.8% versus NCX-4040+cisplatin, 26.4 +/- 7.6%; p < 0.01) and xenograft tumors (cisplatin alone, 74.0 +/- 4.4% versus NCX-4040+cisplatin, 56.4 +/- 7.8%; p < 0.05), to cisplatin treatment. EPR imaging of tissue redox and thiol measurements showed a 5.5-fold reduction (p < 0.01) of glutathione in NCX-4040-treated A2780 cDDP tumors when compared to untreated controls. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice treated with NCX-4040 and cisplatin revealed significant downregulation of pEGFR (Tyr845 and Tyr992) and pSTAT3 (Tyr705 and Ser727) expression.
conclusionThe results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies.
Indexed as
Identifiers
What OpenQuestion holds
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.