Single-fraction Radiation Treatment Dose Response in a Genetically Engineered Mouse Model of Medulloblastoma.

Autor: Tu, Kevin J., Stewart, Connor E., Williams, Nerissa T., Ma, Yan, Luo, Lixia, Ghosh, Debosir, Weidenhammer, Loren B., Floyd, Scott R., Fan, Yi, Kirsch, David G., Oldham, Mark, Reitman, Zachary J.
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Zdroj: Radiation Research; Dec2023, Vol. 200 Issue 6, p587-592, 6p
Abstrakt: Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and other adverse effects. The pathophysiological mechanisms involved in radiation-induced cerebral damage are incompletely understood, and their elucidation may lead to interventions that mitigate radiation toxicity. To explore the mechanisms of radiation-induced cerebral damage, transgenic mouse models of PM and non-tumor-bearing controls were exposed to radiation doses that ranged from 0 to 30 Gy. Between 0–20 Gy, a significant dose-dependent reduction in tumor-associated hydrocephalus and increase in overall survival were observed. However, at 30 Gy, hydrocephalus incidence increased and median overall survival fell to near-untreated levels. Immunohistochemistry revealed that both tumor-bearing and non-tumor-bearing mice treated with 30 Gy of radiation had significantly more reactive astrocytes and microvascular damage compared to untreated controls. This effect was persistent across mice that were given 1 and 2 weeks of recovery time after irradiation. Our data suggest that radiation therapy promotes neural death by inducing long-term neuroinflammation in PM, suggesting radiation delivery methods that limit inflammation may be effective at widening the therapeutic window of radiation therapy in PM patients. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index