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Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma
BACKGROUND: Conventional radiation therapy for glioblastoma (GBM) has limited efficacy. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated rad...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635404/ https://www.ncbi.nlm.nih.gov/pubmed/37961626 http://dx.doi.org/10.21203/rs.3.rs-3500563/v1 |
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author | Lan, Xiao-Yan Kalkowski, Lukasz Chu, Cheng-Yan Jablonska, Anna Li, Shen Kai, Mihoko Gao, Yue Janowski, Miroslaw Walczak, Piotr |
author_facet | Lan, Xiao-Yan Kalkowski, Lukasz Chu, Cheng-Yan Jablonska, Anna Li, Shen Kai, Mihoko Gao, Yue Janowski, Miroslaw Walczak, Piotr |
author_sort | Lan, Xiao-Yan |
collection | PubMed |
description | BACKGROUND: Conventional radiation therapy for glioblastoma (GBM) has limited efficacy. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated radiation on brain injury and tumor responses in immunocompetent mice. We also evaluated the role of the HIF-1α under radiation. METHODS: Naïve and hypoxia-inducible factor-1 alpha (HIF-1α)(+/−) heterozygous mice received a fractionated daily dose of 20 Gy for three or five consecutive days. Magnetic resonance imaging (MRI) and histology were performed to assess brain injury post-radiation. The 2×10(5) human GBM1 luciferase-expressing cells were transplanted with tolerance induction protocol. Fractionated radiotherapy was performed during the exponential phase of tumor growth. BLI, MRI, and immunohistochemistry staining were performed to evaluate tumor growth dynamics and radiotherapy responses. Additionally, animal lifespan was recorded. RESULTS: Fractionated radiation of 5×20 Gy induced severe brain damage, starting 3 weeks after radiation. All animals from this group died within 12 weeks. In contrast, later onset and less severe brain injury were observed starting 12 weeks after radiation of 3×20 Gy. It resulted in complete GBM eradication and survival of all treated animals. Furthermore, HIF-1α(+/−) mice exhibited more obvious vascular damage 63 weeks after fractionated radiation of 3×20 Gy. CONCLUSION: Ultra-high dose fractionated 3×20 Gy radiation can eradicate the GBM cells at the cost of only mild brain injury. The HIF-1α gene is a promising target for ameliorating vascular impairment post-radiation, encouraging the implementation of neurorestorative strategies. |
format | Online Article Text |
id | pubmed-10635404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-106354042023-11-13 Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma Lan, Xiao-Yan Kalkowski, Lukasz Chu, Cheng-Yan Jablonska, Anna Li, Shen Kai, Mihoko Gao, Yue Janowski, Miroslaw Walczak, Piotr Res Sq Article BACKGROUND: Conventional radiation therapy for glioblastoma (GBM) has limited efficacy. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated radiation on brain injury and tumor responses in immunocompetent mice. We also evaluated the role of the HIF-1α under radiation. METHODS: Naïve and hypoxia-inducible factor-1 alpha (HIF-1α)(+/−) heterozygous mice received a fractionated daily dose of 20 Gy for three or five consecutive days. Magnetic resonance imaging (MRI) and histology were performed to assess brain injury post-radiation. The 2×10(5) human GBM1 luciferase-expressing cells were transplanted with tolerance induction protocol. Fractionated radiotherapy was performed during the exponential phase of tumor growth. BLI, MRI, and immunohistochemistry staining were performed to evaluate tumor growth dynamics and radiotherapy responses. Additionally, animal lifespan was recorded. RESULTS: Fractionated radiation of 5×20 Gy induced severe brain damage, starting 3 weeks after radiation. All animals from this group died within 12 weeks. In contrast, later onset and less severe brain injury were observed starting 12 weeks after radiation of 3×20 Gy. It resulted in complete GBM eradication and survival of all treated animals. Furthermore, HIF-1α(+/−) mice exhibited more obvious vascular damage 63 weeks after fractionated radiation of 3×20 Gy. CONCLUSION: Ultra-high dose fractionated 3×20 Gy radiation can eradicate the GBM cells at the cost of only mild brain injury. The HIF-1α gene is a promising target for ameliorating vascular impairment post-radiation, encouraging the implementation of neurorestorative strategies. American Journal Experts 2023-11-01 /pmc/articles/PMC10635404/ /pubmed/37961626 http://dx.doi.org/10.21203/rs.3.rs-3500563/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Lan, Xiao-Yan Kalkowski, Lukasz Chu, Cheng-Yan Jablonska, Anna Li, Shen Kai, Mihoko Gao, Yue Janowski, Miroslaw Walczak, Piotr Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma |
title | Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma |
title_full | Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma |
title_fullStr | Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma |
title_full_unstemmed | Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma |
title_short | Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma |
title_sort | unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635404/ https://www.ncbi.nlm.nih.gov/pubmed/37961626 http://dx.doi.org/10.21203/rs.3.rs-3500563/v1 |
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