- AutorIn
- Marieke Gringmuth
- Jenny Walther
- Sebastian Greiser
- Magali Touissant
- Benjamin Schwalm
- Marcel Kool
- Rolf-Dieter Kortmann
- Annegret Glasow
- Ina Patties
- Titel
- Enhanced Survival of High-Risk Medulloblastoma-Bearing Mice after Multimodal Treatment with Radiotherapy, Decitabine, and Abacavir
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-891632
- Quellenangabe
- International Journal of Molecular Sciences
Erscheinungsjahr: 2022
Jahrgang: 23
Artikelnummer: 3815 - Erstveröffentlichung
- 2022
- Abstract (EN)
- Children with high-risk SHH/TP53-mut and Group 3 medulloblastoma (MB) have a 5-year overall survival of only 40%. Innovative approaches to enhance survival while preventing adverse effects are urgently needed. We investigated an innovative therapy approach combining irradia- tion (RT), decitabine (DEC), and abacavir (ABC) in a patient-derived orthotopic SHH/TP53-mut and Group 3 MB mouse model. MB-bearing mice were treated with DEC, ABC and RT. Mouse survival, tumor growth (BLI, MRT) tumor histology (H/E), proliferation (Ki-67), and endothelial (CD31) staining were analyzed. Gene expression was examined by microarray and RT-PCR (Ki-67, VEGF, CD31, CD15, CD133, nestin, CD68, IBA). The RT/DEC/ABC therapy inhibited tumor growth and enhanced mouse survival. Ki-67 decreased in SHH/TP53-mut MBs after RT, DEC, RT/ABC, and RT/DEC/ABC therapy. CD31 was higher in SHH/TP53-mut compared to Group 3 MBs and decreased after RT/DEC/ABC. Microarray analyses showed a therapy-induced downregulation of cell cycle genes. By RT-PCR, no therapy-induced effect on stem cell fraction or immune cell inva- sion/activation could be shown. We showed for the first time that RT/DEC/ABC therapy improves survival of orthotopic SHH/TP53-mut and Group 3 MB-bearing mice without inducing adverse effects suggesting the potential for an adjuvant application of this multimodal therapy approach in the human clinic.
- Andere Ausgabe
- Link zur Erstveröffentlichung
Link: https://doi.org/10.3390/ijms23073815 - Freie Schlagwörter (EN)
- medulloblastoma; radiation; decitabine; abacavir; in vivo study; magnetic resonance imaging; T2 mapping; bioluminescence imaging; gene expression microarray
- Klassifikation (DDC)
- 610
- Verlag
- MDPI, Basel
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-891632
- Veröffentlichungsdatum Qucosa
- 20.01.2024
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
- CC BY 4.0