Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma.
brain injury
fractionated radiation
glioblastoma
hypoxia-inducible factor
vascular damage
Journal
Research square
Titre abrégé: Res Sq
Pays: United States
ID NLM: 101768035
Informations de publication
Date de publication:
01 Nov 2023
01 Nov 2023
Historique:
pubmed:
14
11
2023
medline:
14
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
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. Naïve and hypoxia-inducible factor-1 alpha (HIF-1α) 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 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.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
Naïve and hypoxia-inducible factor-1 alpha (HIF-1α)
Results
UNASSIGNED
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
Conclusion
UNASSIGNED
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.
Identifiants
pubmed: 37961626
doi: 10.21203/rs.3.rs-3500563/v1
pmc: PMC10635404
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102675
Pays : United States
Déclaration de conflit d'intérêts
Declarations Competing interests Miroslaw Janowski and Piotr Walczak are co-founders and co-owners of IntraART, LLC and Ti-Com, LLC., but they are not directly related to the content of this study. Other co-authors declare no potential conflict of interest.
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