ArticleProceedings of the National Academy of Sciences of the United States of America2016
Hypoxia-activated cytotoxic agent tirapazamine enhances hepatic artery ligation-induced killing of liver tumor in HBx transgenic mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- Phase I Trial on Arterial Embolization with Hypoxia Activated Tirapazamine for Unresectable Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2021Trial
- Calcification-Mediated Dual-Starvation and Immune Activation for Transarterial Chemoembolization.International journal of nanomedicine · 2026Article
- Combination of vascular surgery with novel vascular targeting agents as cancer therapeutics.Frontiers in oncology · 2025Review
- Article
- Hypoxia as a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Introducing urea into tirapazamine derivatives to enhance anticancer therapy.National science review · 2024Article
- Drug-Eluting Porous Embolic Microspheres for Trans-Arterial Delivery of Dual Synergistic Anticancer Therapy for the Treatment of Liver Cancer.Advanced healthcare materials · 2023Article
- Sonocatalytic Optimization of Titanium-Based Therapeutic Nanomedicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Article
- Review
- TIDE: adjuvant tislelizumab plus donafenib combined with transarterial chemoembolization for high-risk hepatocellular carcinoma after surgery: protocol for a prospective, single-arm, phase II trial.Frontiers in oncology · 2023Article
- Tirapazamine-loaded CalliSpheres microspheres: Preparation and characterization as a chemoembolization agent for liver cancer.MethodsX · 2023Article
- SOCS5 knockdown suppresses metastasis of hepatocellular carcinoma by ameliorating HIF-1α-dependent mitochondrial damage.Cell death & disease · 2022Article
- Interventional oncology: new techniques and new devices.The British journal of radiology · 2022Review
- Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma.Journal of vascular and interventional radiology : JVIR · 2022Article
- Targeting Hypoxia: Revival of Old Remedies.Biomolecules · 2021Review
- A rat toxicological study of intra-arterial injection of Tirapazamine, a hypoxia-activating Cancer therapeutic agent, followed by hepatic artery ligation.Investigational new drugs · 2021Article
- Type of Necrosis Influences Prognosis in Hepatocellular Carcinoma After the First Transarterial Chemoembolization.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Erythrocyte-Camouflaged Mesoporous Titanium Dioxide Nanoplatform for an Ultrasound-Mediated Sequential Therapies of Breast Cancer.International journal of nanomedicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transarterial chemoembolization (TACE) is the main treatment for intermediate stage hepatocellular carcinoma (HCC) with Barcelona Clinic Liver Cancer classification because of its exclusive arterial blood supply. Although TACE achieves substantial necrosis of the tumor, complete tumor necrosis is uncommon, and the residual tumor generally rapidly recurs. We combined tirapazamine (TPZ), a hypoxia-activated cytotoxic agent, with hepatic artery ligation (HAL), which recapitulates transarterial embolization in mouse models, to enhance the efficacy of TACE. The effectiveness of this combination treatment was examined in HCC that spontaneously developed in hepatitis B virus X protein (HBx) transgenic mice. We proved that the tumor blood flow in this model was exclusively supplied by the hepatic artery, in contrast to conventional orthotopic HCC xenografts that receive both arterial and venous blood supplies. At levels below the threshold oxygen levels created by HAL, TPZ was activated and killed the hypoxic cells, but spared the normoxic cells. This combination treatment clearly limited the toxicity of TPZ to HCC, which caused the rapid and near-complete necrosis of HCC. In conclusion, the combination of TPZ and HAL showed a synergistic tumor killing activity that was specific for HCC in HBx transgenic mice. This preclinical study forms the basis for the ongoing clinical program for the TPZ-TACE regimen in HCC treatment.
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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.