@article{SchmittEckardtSchlegeletal.2015,
  author    = {Schmitt, Jessica and Eckardt, Sigrid and Schlegel, Paul G and Sir{\´e}n, Anna-Leena and Bruttel, Valentin S and McLaughlin, K John and Wischhusen, J{\"o}rg and M{\"u}ller, Albrecht M},
  title     = {Human parthenogenetic embryonic stem cell-derived neural stem cells express HLA-G and show unique resistance to NK cell-mediated killing},
  series = {Molecular Medicine},
  volume    = {21},
  journal   = {Molecular Medicine},
  number    = {2101185},
  doi       = {10.2119/molmed.2014.00188},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149170},
  pages     = {185-196},
  year      = {2015},
  abstract  = {Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro mixed lymphocyte reaction assay resulted in less proliferation of peripheral blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression analyses of immune regulatory factors revealed higher HLA-G levels in PG compared with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG NSCs. Together this indicates that PG NSCs have unique immunological properties due to elevated HLA-G expression.},
  language  = {en}
}
@article{SchwinnMokhtariThuseketal.2021,
  author    = {Schwinn, Stefanie and Mokhtari, Zeinab and Thusek, Sina and Schneider, Theresa and Sir{\´e}n, Anna-Leena and Tiemeyer, Nicola and Caruana, Ignazio and Miele, Evelina and Schlegel, Paul G. and Beilhack, Andreas and W{\"o}lfl, Matthias},
  title     = {Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-93586-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261476},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}