TY - JOUR A1 - Dietl, Sebastian A1 - Schwinn, Stefanie A1 - Dietl, Susanne A1 - Riedl, Simone A1 - Deinlein, Frank A1 - Rutkowski, Stefan A1 - von Bueren, Andre O. A1 - Krauss, Jürgen A1 - Schweitzer, Tilmann A1 - Vince, Giles H. A1 - Picard, Daniel A1 - Eyrich, Matthias A1 - Rosenwald, Andreas A1 - Ramaswamy, Vijay A1 - Taylor, Michael D. A1 - Remke, Marc A1 - Monoranu, Camelia M. A1 - Beilhack, Andreas A1 - Schlegel, Paul G. A1 - Wölfl, Matthias T1 - MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties JF - BMC Cancer N2 - Background Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. Methods We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. Results Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. Conclusions This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma. KW - cancer stem cells KW - anaplastic medulloblastoma KW - group 3 KW - orthotopic xenograft KW - animal model KW - brain tumor KW - children Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145877 VL - 16 IS - 115 ER - TY - JOUR A1 - Schwinn, Stefanie A1 - Mokhtari, Zeinab A1 - Thusek, Sina A1 - Schneider, Theresa A1 - Sirén, Anna-Leena A1 - Tiemeyer, Nicola A1 - Caruana, Ignazio A1 - Miele, Evelina A1 - Schlegel, Paul G. A1 - Beilhack, Andreas A1 - Wölfl, Matthias T1 - Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma JF - Scientific Reports N2 - 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 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. KW - cancer KW - CNS cancer KW - paediatric cancer Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261476 VL - 11 IS - 1 ER -