Journal article
Rapid Peroxide Removal Limits the Radiosensitization of Diffuse Intrinsic Pontine Glioma (DIPG) Cells by Pharmacologic Ascorbate
Radiation research, Vol.200(5), pp.456-461
11/2023
DOI: 10.1667/RADE-23-00006.1
PMCID: PMC10759934
PMID: 37758035
Abstract
Diffuse intrinsic pontine gliomas (DIPG) are an aggressive type of pediatric brain tumor with a very high mortality rate. Surgery has a limited role given the tumor’s location. Palliative radiation therapy alleviates symptoms and prolongs survival, but median survival remains less than 1 year. There is no clear role for chemotherapy in DIPGs as trials adding chemotherapy to palliative radiation therapy have failed to improve survival compared to radiation alone. Thus, there is a critical need to identify tissue-specific radiosensitizers to improve clinical outcomes for patients with DIPGs. Pharmacologic (high dose) ascorbate (P-AscH–) is a promising anticancer therapy that sensitizes human tumors, including adult high-grade gliomas, to radiation by acting selectively as a generator of hydrogen peroxide (H2O2) in cancer cells. In this study we demonstrate that in contrast to adult glioma models, P-AscH– does not radiosensitize DIPG. DIPG cells were sensitive to bolus of H2O2 but have faster H2O2 removal rates than GBM models which are radiosensitized by P-AscH–. These data support the hypothesis that P-AscH– does not enhance DIPG radiosensitivity, likely due to a robust capacity to detoxify and remove hydroperoxides.
Details
- Title: Subtitle
- Rapid Peroxide Removal Limits the Radiosensitization of Diffuse Intrinsic Pontine Glioma (DIPG) Cells by Pharmacologic Ascorbate
- Creators
- Shane R. Solst - University of IowaKranti A. Mapuskar - University of IowaClaire H. Graham - University of IowaSarah A. King - University of IowaRana Rheem - University of IowaKyle Current - University of IowaBryan G. Allen - University of IowaJoseph M. Caster - University of IowaDouglas R. Spitz - University of IowaMichelle E. Howard - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Radiation research, Vol.200(5), pp.456-461
- DOI
- 10.1667/RADE-23-00006.1
- PMID
- 37758035
- PMCID
- PMC10759934
- NLM abbreviation
- Radiat Res
- ISSN
- 0033-7587
- eISSN
- 1938-5404
- Language
- English
- Electronic publication date
- 09/27/2023
- Date published
- 11/2023
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984473951202771
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