ArticleCancer science2012
Carbon monoxide, generated by heme oxygenase-1, mediates the enhanced permeability and retention effect in solid tumors.
Article in Cancer science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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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
33 citing papers in PubMed, 83 citations in OpenAlex.
- Avenues for integrating photothermal therapy in cancer clinic.Communications chemistry · 2025Review
- Reactive oxygen species responsive nanomotors for gene edited metabolic disruption and immunotherapy.Nature communications · 2025Article
- The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023Review
- Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors.Journal of personalized medicine · 2022Review
- Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.Journal of oncology · 2022Review
- Styrene Maleic Acid Copolymer-Based Micellar Formation of Temoporfin (SMA@ mTHPC) Behaves as A Nanoprobe for Tumor-Targeted Photodynamic Therapy with A Superior Safety.Biomedicines · 2021Article
- Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment.Journal of personalized medicine · 2021Review
- Candesartan treatment enhances liposome penetration and anti-tumor effect via depletion of tumor stroma and normalization of tumor vessel.Drug delivery and translational research · 2021Article
- Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect.Journal of personalized medicine · 2021Review
- One-step, Rapid and Green Synthesis of Multifunctional Gold Nanoparticles for Tumor-Targeted Imaging and Therapy.Nanoscale research letters · 2020Article
- Augmentation of EPR Effect and Efficacy of Anticancer Nanomedicine by Carbon Monoxide Generating Agents.Pharmaceutics · 2019Article
- Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application.Acta pharmaceutica Sinica. B · 2019Review
- Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency.Cancers · 2019Review
- Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment.Journal of personalized medicine · 2018Review
- Tumor-penetrating peptide enhances transcytosis of silicasome-based chemotherapy for pancreatic cancer.The Journal of clinical investigation · 2017Article
- Nanocaged platforms: modification, drug delivery and nanotoxicity. Opening synthetic cages to release the tiger.Nanoscale · 2017Review
- Aspects of Carbon Monoxide in Form of CO-Releasing Molecules Used in Cancer Treatment: More Light on the Way.Oxidative medicine and cellular longevity · 2017Review
- Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer?Bioconjugate chemistry · 2016Review
- An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors.Scientific reports · 2016Article
- Curcumin and Resveratrol as Promising Natural Remedies with Nanomedicine Approach for the Effective Treatment of Triple Negative Breast Cancer.Journal of oncology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enhanced permeability and retention (EPR) effect is a unique pathophysiological phenomenon of solid tumors that sees biocompatible macromolecules (>40 kDa) accumulate selectively in the tumor. Various factors have been implicated in this effect. Herein, we report that heme oxygenase-1 (HO-1; also known as heat shock protein 32) significantly increases vascular permeability and thus macromolecular drug accumulation in tumors. Intradermal injection of recombinant HO-1 in mice, followed by i.v. administration of a macromolecular Evans blue-albumin complex, resulted in dose-dependent extravasation of Evans blue-albumin at the HO-1 injection site. Almost no extravasation was detected when inactivated HO-1 or a carbon monoxide (CO) scavenger was injected instead. Because HO-1 generates CO, these data imply that CO plays a key role in vascular leakage. This is supported by results obtained after intratumoral administration of a CO-releasing agent (tricarbonyldichlororuthenium(II) dimer) in the same experimental setting, specifically dose-dependent increases in vascular permeability plus augmented tumor blood flow. In addition, induction of HO-1 in tumors by the water-soluble macromolecular HO-1 inducer pegylated hemin significantly increased tumor blood flow and Evans blue-albumin accumulation in tumors. These findings suggest that HO-1 and/or CO are important mediators of the EPR effect. Thus, anticancer chemotherapy using macromolecular drugs may be improved by combination with an HO-1 inducer, such as pegylated hemin, via an enhanced EPR effect.
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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.