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@ARTICLE{Arians:144414,
      author       = {N. Arians$^*$ and N. H. Nicolay$^*$ and S. Brons and S. A.
                      Koerber and C. Jaschke and M. Vercruysse and S. Daffinger
                      and A. Rühle$^*$ and J. Debus$^*$ and K. Lindel},
      title        = {{C}arbon-ion irradiation overcomes {HPV}-integration/{E}2
                      gene-disruption induced radioresistance of cervical
                      keratinocytes.},
      journal      = {Journal of radiation research},
      volume       = {60},
      number       = {5},
      issn         = {1349-9157},
      address      = {Kawaguchi},
      publisher    = {J-STAGE},
      reportid     = {DKFZ-2019-01867},
      pages        = {564-572},
      year         = {2019},
      note         = {J Radiat Res. 2019 Oct 23;60(5):564-572},
      abstract     = {To date, only few data exist on mechanisms underlying the
                      human papillomavirus (HPV)-associated irradiation response.
                      It has been suggested, that the viral E2 gene plays an
                      important role in that context. The aim of the current study
                      is to compare the effect of photon- and carbon-ion
                      (12C)-radiation therapy (RT) on cells with different HPV and
                      E2 gene status. We hypothesized that 12C-RT might overcome
                      the radioresistance of E2 gene-disrupted cells. We analyzed
                      four different cell lines that differed in HPV status or E2
                      gene status. Cells were irradiated with either photons or
                      12C. Clonogenic survival, cell cycle and expression of Rb
                      and p53 were analyzed. Radiosensitivity seemed to be
                      dependent on E2 gene status and type of RT. 12C-RT led to
                      lower surviving fractions, indicating higher
                      radiosensitivity even in cells with disrupted E2 gene. The
                      observed relative biological effectiveness (RBE) of 12C-RT
                      for C33a/Caski and W12/S12 was 1.3/4 and 2.7/2.5,
                      respectively. Cell cycle regulation after both photon- and
                      12C-RT was dependent on HPV status and on E2 gene status.
                      Furthermore, the effect of RT on expression of p53 and Rb
                      seemed to be dependent on E2 gene status and type of RT. We
                      showed that 12C-RT overcomes HPV-integration induced
                      radioresistance. The effect of RT on cell cycle regulation
                      as well as on expression of p53 and Rb seemed to be
                      dependent on HPV status, E2 gene status and type of RT.
                      Differences in Rb expression and cell cycle regulation may
                      play a role for enhanced radiosensitivity to 12C-RT of cells
                      with disrupted E2 gene.},
      cin          = {E050 / L101 / E055},
      ddc          = {610},
      cid          = {I:(DE-He78)E050-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)E055-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31322705},
      doi          = {10.1093/jrr/rrz048},
      url          = {https://inrepo02.dkfz.de/record/144414},
}