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@ARTICLE{Lacroix:127880,
      author       = {J. A. D. Lacroix$^*$ and F. Schlund$^*$ and B. Leuchs$^*$
                      and K. Adolph$^*$ and D. Sturm$^*$ and S. Bender$^*$ and T.
                      Hielscher$^*$ and S. Pfister$^*$ and O. Witt$^*$ and J.
                      Rommelaere$^*$ and J. R. Schlehofer$^*$ and H. Witt$^*$},
      title        = {{O}ncolytic effects of parvovirus {H}-1 in medulloblastoma
                      are associated with repression of master regulators of early
                      neurogenesis.},
      journal      = {International journal of cancer},
      volume       = {134},
      number       = {3},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-03902},
      pages        = {703 - 716},
      year         = {2014},
      abstract     = {Based on extensive pre-clinical studies, the oncolytic
                      parvovirus H-1 (H-1PV) is currently applied to patients with
                      recurrent glioblastoma in a phase I/IIa clinical trial
                      (ParvOryx01, NCT01301430). Cure rates of about $40\%$ in
                      pediatric high-risk medulloblastoma (MB) patients also
                      indicate the need of new therapeutic approaches. In order to
                      prepare a future application of oncolytic parvovirotherapy
                      to MB, the present study preclinically evaluates the
                      cytotoxic efficacy of H-1PV on MB cells in vitro and
                      characterizes cellular target genes involved in this effect.
                      Six MB cell lines were analyzed by whole genome
                      oligonucleotide microarrays after treatment and the results
                      were matched to known molecular and cytogenetic risk
                      factors. In contrast to non-transformed infant astrocytes
                      and neurons, in five out of six MB cell lines lytic H-1PV
                      infection and efficient viral replication could be
                      demonstrated. The cytotoxic effects induced by H-1PV were
                      observed at LD50s below 0.05 p. f. u. per cell indicating
                      high susceptibility. Gene expression patterns in the
                      responsive MB cell lines allowed the identification of
                      candidate target genes mediating the cytotoxic effects of
                      H-1PV. H-1PV induced down-regulation of key regulators of
                      early neurogenesis shown to confer poor prognosis in MB such
                      as ZIC1, FOXG1B, MYC, and NFIA. In MB cell lines with
                      genomic amplification of MYC, expression of MYC was the
                      single gene most significantly repressed after H-1PV
                      infection. H-1PV virotherapy may be a promising treatment
                      approach for MB since it targets genes of functional
                      relevance and induces cell death at very low titers of input
                      virus.},
      cin          = {F010 / D015 / B062 / C060 / G340},
      ddc          = {610},
      cid          = {I:(DE-He78)F010-20160331 / I:(DE-He78)D015-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)G340-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:23852775},
      pmc          = {pmc:PMC4232887},
      doi          = {10.1002/ijc.28386},
      url          = {https://inrepo02.dkfz.de/record/127880},
}