Tumour reoxygenation after intratumoural hydrogen peroxide (KORTUC) injection: a novel approach to enhance radiosensitivity

Background KORTUC (0.5% hydrogen peroxide (H 2 O 2 ) in 1% sodium-hyaluronate) releases cytotoxic levels of H 2 O 2 in tissues after intratumoural injection. High levels of tumour control after radiotherapy plus KORTUC are reported in breast cancer patients. Here, we use human xenograft models to te...

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Veröffentlicht in:BJC reports Jg. 2; H. 1; S. 78 - 9
Hauptverfasser: Nimalasena, Samantha, Anbalagan, Selvakumar, Box, Carol, Yu, Sheng, Boult, Jessica K. R., Bush, Nigel, Howell, Louise, Sinnett, Victoria, Murphy, William, Yarnold, John, Robinson, Simon P., Somaiah, Navita
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 08.10.2024
Nature Publishing Group
Nature Portfolio
Schlagworte:
Animals
Antibodies
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell culture
Experiments
Hydrogen peroxide
Hypoxia
Medical research
Oncology
Radiation
Sodium
Software
Spheroids
Tumors
Ultrasonic imaging
United Kingdom > UK
United States > US
Fiji
ISSN:2731-9377, 2731-9377
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Zusammenfassung:Background KORTUC (0.5% hydrogen peroxide (H 2 O 2 ) in 1% sodium-hyaluronate) releases cytotoxic levels of H 2 O 2 in tissues after intratumoural injection. High levels of tumour control after radiotherapy plus KORTUC are reported in breast cancer patients. Here, we use human xenograft models to test the hypothesis that oxygen microbubbles released post-KORTUC are effective in modifying the hypoxic tumour microenvironment. Methods and materials Pimonidazole and Image-iT™ Red (live hypoxia marker) were utilised to assess dose-dependent changes in hypoxia post-H 2 O 2 in HCT116 and LICR-LON-HN5 spheroids. Using a dual 2-nitroimidazole-marker technique and phospho-ATM we evaluated changes in hypoxia and reactive oxygen species (ROS) respectively, in HCT116 and LICR-LON-HN5 xenografts following intratumoural KORTUC. Results A significant reduction in Image-iT™ Red fluorescence was observed in spheroids 1 h post-H 2 O 2 at ≥1.2 mM, maintained at 24 h. Ultrasound demonstrated sustained release of oxygen microbubbles within tumours, 1 h post-KORTUC. Hypoxia markers demonstrated significant tissue reoxygenation in both models post-KORTUC and significantly increased phospho-ATM foci reflecting increased ROS production. Conclusion Intratumoural KORTUC represents a novel oxygen delivery method, which can be exploited to enhance radiation response. If efficacy is confirmed in the ongoing phase 2 breast trial it could improve treatment of several tumour types where hypoxia is known to affect radiotherapy outcomes.
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ISSN:2731-9377
2731-9377
DOI:10.1038/s44276-024-00098-y