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Gringmuth, Marieke [VerfasserIn]; Walther, Jenny [VerfasserIn]; Greiser, Sebastian [VerfasserIn]; Touissant, Magali [VerfasserIn]; Schwalm, Benjamin [VerfasserIn]; Kool, Marcel [VerfasserIn]; Kortmann, Rolf-Dieter [VerfasserIn]; Glasow, Annegret [VerfasserIn]; Patties, Ina [VerfasserIn]

Enhanced Survival of High-Risk Medulloblastoma-Bearing Mice after Multimodal Treatment with Radiotherapy, Decitabine, and Abacavir

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  • Medientyp: E-Artikel
  • Titel: Enhanced Survival of High-Risk Medulloblastoma-Bearing Mice after Multimodal Treatment with Radiotherapy, Decitabine, and Abacavir
  • Beteiligte: Gringmuth, Marieke [VerfasserIn]; Walther, Jenny [VerfasserIn]; Greiser, Sebastian [VerfasserIn]; Touissant, Magali [VerfasserIn]; Schwalm, Benjamin [VerfasserIn]; Kool, Marcel [VerfasserIn]; Kortmann, Rolf-Dieter [VerfasserIn]; Glasow, Annegret [VerfasserIn]; Patties, Ina [VerfasserIn]
  • Erschienen: Basel : MDPI, [2024]
  • Sprache: Englisch
  • Schlagwörter: medulloblastoma; radiation; decitabine; abacavir; in vivo study; magnetic resonance imaging; T2 mapping; bioluminescence imaging; gene expression microarray ; Medizin ; medicine
  • Entstehung:
  • Anmerkungen: Hinweis: Link zur Erstveröffentlichung URL: https://doi.org/10.3390/ijms23073815
  • Beschreibung: 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.
  • Zugangsstatus: Freier Zugang
  • Rechte-/Nutzungshinweise: Namensnennung (CC BY)