ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2026
Relative biological effectiveness and neural stem cell fate in carbon ion-irradiated human brain organoids.
Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
background and purposeHeavy ion therapy offers a promising approach for treating brain tumors due to the high precision of ion beams and biological effectiveness. However, the mechanisms underlying contrast-enhanced brain lesions, which occur more frequently after ions than conventional X-rays, remain to be elucidated. MATERIALS AND
methodsCerebral organoids were generated from human embryonic stem cells and exposed to high-energy carbon-ions at early (day 20) and late (day 80) developmental stages. Analyses of gene expression were performed using RT-PCR analysis, and protein expression was assessed using immunofluorescence staining.
resultsWe demonstrate that exposure to high-energy carbon (C)-ions induces the formation of ectopic choroid plexus (CP)-like structures in human cerebral organoids. RT-PCR analyses revealed that C-ion exposure alters the differentiation trajectories of neuroepithelial stem cells, driven by dysregulation of key developmental signaling pathways including NOTCH, WNT, and BMP. Moreover, we observed increased expression of CP-associated markers AQP1 and CLDN3. The relative biological effectiveness (RBE) of C-ions for the formation of fluid-filled cavities associated with CP-like tissue was calculated as 2.0 after both 60 and 100 days of differentiation.
conclusionOur findings indicate that aberrant CP development is a central mechanism underlying post-radiation contrast-enhanced brain lesions, and that an RBE of 2 should be considered when determining dose thresholds for normal tissue tolerance in carbon ion therapy for brain tumors.
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