The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 1 of 85
Back to Result List

Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-261476
  • Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that areMedulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Stefanie Schwinn, Zeinab Mokhtari, Sina Thusek, Theresa Schneider, Anna-Leena Sirén, Nicola Tiemeyer, Ignazio Caruana, Evelina Miele, Paul G. Schlegel, Andreas Beilhack, Matthias Wölfl
URN:urn:nbn:de:bvb:20-opus-261476
Document Type:Journal article
Faculties:Medizinische Fakultät / Kinderklinik und Poliklinik
Medizinische Fakultät / Neurochirurgische Klinik und Poliklinik
Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Scientific Reports
Year of Completion:2021
Volume:11
Issue:1
Article Number:14062
Source:Scientific Reports (2021) 11:1, 14062. https://doi.org/10.1038/s41598-021-93586-x
DOI:https://doi.org/10.1038/s41598-021-93586-x
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 618 Gynäkologie, Geburtsmedizin, Pädiatrie, Geriatrie
Tag:CNS cancer; cancer; paediatric cancer
Release Date:2022/04/07
Open-Access-Publikationsfonds / Förderzeitraum 2021
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International