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@ARTICLE{Krex:274214,
      author       = {D. Krex$^*$ and P. Bartmann and D. Lachmann and A. Hagstotz
                      and W. Jugel and R. S. Schneiderman and K. Gotlib and Y.
                      Porat and K. Robel and A. Temme$^*$ and M. Giladi and S.
                      Michen},
      title        = {{A}urora {B} {K}inase {I}nhibition by {AZD}1152
                      {C}oncomitant with {T}umor {T}reating {F}ields {I}s
                      {E}ffective in the {T}reatment of {C}ultures from {P}rimary
                      and {R}ecurrent {G}lioblastomas.},
      journal      = {International journal of molecular sciences},
      volume       = {24},
      number       = {5},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2023-00500},
      pages        = {5016},
      year         = {2023},
      abstract     = {Tumor Treating Fields (TTFields) were incorporated into the
                      treatment of glioblastoma, the most malignant brain tumor,
                      after showing an effect on progression-free and overall
                      survival in a phase III clinical trial. The combination of
                      TTFields and an antimitotic drug might further improve this
                      approach. Here, we tested the combination of TTFields with
                      AZD1152, an Aurora B kinase inhibitor, in primary cultures
                      of newly diagnosed (ndGBM) and recurrent glioblastoma
                      (rGBM). AZD1152 concentration was titrated for each cell
                      line and 5-30 nM were used alone or in addition to TTFields
                      (1.6 V/cm RMS; 200 kHz) applied for 72 h using the
                      inovitro™ system. Cell morphological changes were
                      visualized by conventional and confocal laser microscopy.
                      The cytotoxic effects were determined by cell viability
                      assays. Primary cultures of ndGBM and rGBM varied in p53
                      mutational status; ploidy; EGFR expression and MGMT-promoter
                      methylation status. Nevertheless; in all primary cultures; a
                      significant cytotoxic effect was found following TTFields
                      treatment alone and in all but one, a significant effect
                      after treatment with AZD1152 alone was also observed.
                      Moreover, in all primary cultures the combined treatment had
                      the most pronounced cytotoxic effect in parallel with
                      morphological changes. The combined treatment of TTFields
                      and AZD1152 led to a significant reduction in the number of
                      ndGBM and rGBM cells compared to each treatment alone.
                      Further evaluation of this approach, which has to be
                      considered as a proof of concept, is warranted, before
                      entering into early clinical trials.},
      keywords     = {AZD1152 (Other) / Aurora B kinase (Other) / TTFields
                      (Other) / glioblastoma (Other) / primary cultures (Other)},
      cin          = {DD01},
      ddc          = {540},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36902447},
      doi          = {10.3390/ijms24055016},
      url          = {https://inrepo02.dkfz.de/record/274214},
}