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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...

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Autores principales: Lan, Xiao-Yan, Kalkowski, Lukasz, Chu, Cheng-Yan, Jablonska, Anna, Li, Shen, Kai, Mihoko, Gao, Yue, Janowski, Miroslaw, Walczak, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
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.
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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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