ArticleCancer science2008
TS-1 enhances the effect of radiotherapy by suppressing radiation-induced hypoxia-inducible factor-1 activation and inducing endothelial cell apoptosis.
Article in Cancer science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Definitive S-1/mitomycin-C chemoradiotherapy for stage II/III anal canal squamous cell carcinoma: a phase I/II dose-finding and single-arm confirmatory study (JCOG0903).International journal of clinical oncology · 2023Trial
- Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT.Nuclear medicine communications · 2010Trial
- Quantitative dissection of radioresistance in cancer cells: Oxygen depletion-induced biological versus chemical mechanisms and baseline mechanisms governed by HIF-1β-NRF2/TXNRD1.Neoplasia (New York, N.Y.) · 2026Article
- TS-1 inhibits endometrial cancer cell proliferation, migration, and apoptosis by blocking the PI3K/AKT/mTOR signaling pathway.American journal of translational research · 2025Article
- Early glottic cancer treatment with concurrent chemoradiotherapy with once-daily orally administered S-1.Nagoya journal of medical science · 2021Article
- The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies.Journal of clinical medicine · 2021Review
- Short-term outcomes of preoperative chemoradiotherapy with S-1 for locally advanced rectal cancer.Molecular and clinical oncology · 2021Article
- Intensity-modulated radiotherapy for synchronous cancer of the anal canal and cervix.Oncology letters · 2018Article
- Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression.Antioxidants & redox signaling · 2017Article
- Ursolic acid sensitizes radioresistant NSCLC cells expressing HIF-1α through reducing endogenous GSH and inhibiting HIF-1α.Oncology letters · 2017Article
- LY6E: a conductor of malignant tumor growth through modulation of the PTEN/PI3K/Akt/HIF-1 axis.Oncotarget · 2016Article
- Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance.Journal of radiation research · 2016Review
- Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.Oncogene · 2015Article
- A phase I trial of preoperative S-1 in combination with oxaliplatin and pelvic radiation for lower rectal cancer with T4 and lateral pelvic lymph node metastasis.International journal of clinical oncology · 2015Article
- Imaging of CAIX-expressing xenografts in vivo using 99mTc-HEHEHE-ZCAIX:1 affibody molecule.International journal of oncology · 2015Article
- HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs.Scientific reports · 2014Article
- A phase I study of S-1 with concurrent radiotherapy in elderly patients with locally advanced non-small cell lung cancer.Investigational new drugs · 2013Article
- Article
- The irradiated tumor microenvironment: role of tumor-associated macrophages in vascular recovery.Frontiers in physiology · 2013Article
- Microenvironment and radiation therapy.BioMed research international · 2013Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The therapeutic effect of concurrent chemoradiotherapy with TS-1 has been confirmed in various solid tumors; however, the detailed mechanism of action has not yet been fully elucidated. In the present study, we identified hypoxia-inducible factor-1 (HIF-1) as one of the targets of TS-1 in chemoradiotherapy. In growth delay assays using a tumor xenograft of non-small-cell lung carcinoma, H441, TS-1 treatment enhanced the therapeutic effect of single gamma-ray radiotherapy (14 Gy) and significantly delayed tumor growth by 1.58-fold compared to radiotherapy alone (P < 0.01). An optical in vivo imaging experiment using a HIF-1-dependent 5HRE-luc reporter gene revealed that TS-1 treatment suppressed radiation-induced activation of HIF-1 in the tumor xenografts. The suppression led to apoptosis of endothelial cells resulting in both a significant decrease in microvessel density (P < 0.05; vs radiation therapy alone) and a significant increase in apoptosis of tumor cells (P < 0.01; vs radiation therapy alone) in tumor xenografts. All of these results indicate that TS-1 enhances radiation-induced apoptosis of endothelial cells by suppressing HIF-1 activity, resulting in an increase in radiosensitivity of the tumor cells. Our findings strengthen the importance of both HIF-1 and its downstream gene, such as vascular endothelial cell growth factor, as therapeutic targets to enhance the effect of radiotherapy.
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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.