Faithful animal modelling of human glioma by using primary initiating cells and its implications for radiosensitization therapy [ARRIVE 1

Scientific Reports
Guido FrosinaAntonio Daga

Abstract

It has been reported that the ATM kinase inhibitor KU60019 preferentially radiosensitizes orthotopic high grade gliomas (HGG) driven by established U87 and U1242 cell lines bearing specific TP53 mutations. We wished to determine whether those results could be extended to tumors driven by primary glioma initiating cells (GIC) that closely mimic clinical tumors. Orthotopic HGG were developed in immunodeficient non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice by intracranial injection of primary GIC isolated from the adult glioblastoma COMI (acronym of patient's name) and the pediatric anaplastic astrocytoma 239/12. Similar to the clinical tumors of origin, the orthotopic tumors COMI and 239/12 displayed different growth properties with a voluminous expansive lesion that exerted considerable mass effect on the adjacent structures and an infiltrating, gliomatosis-like growth pattern with limited compressive attitude, respectively. Significant elongations of median animal survival bearing the adult COMI tumor was observed after one KU60019 convection enhanced delivery followed by total 7.5 Gy of ionizing radiation delivered in fifteen 0.5 Gy fractions, as compared to animals treated with vehicle + ionizing radiatio...Continue Reading

References

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Citations

Apr 20, 2021·Frontiers in Oncology·Dennis S MetselaarEsther Hulleman
Nov 9, 2021·Journal of Neuroscience Research·Guido FrosinaAntonio Daga

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Methods Mentioned

BETA
X-ray
surgical resection
FCS
biopsy

Software Mentioned

Gpower
Mass Hunter
Mass Hunter Qualitative Analysis
ARRIVE
RadCal
Growing Region Segmentation Software ( GRES )
GRES

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