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@ARTICLE{Bernardo:282351,
      author       = {T. Bernardo and A. Kuntze and D. Klein and F. Heinzelmann
                      and B. Timmermann$^*$ and C. von Neubeck},
      title        = {{E}ndothelial {C}ell {R}esponse to {C}ombined {P}hoton or
                      {P}roton {I}rradiation with {D}oxorubicin.},
      journal      = {International journal of molecular sciences},
      volume       = {24},
      number       = {16},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2023-01735},
      pages        = {12833},
      year         = {2023},
      abstract     = {Surgery, radiotherapy, and chemotherapy are essential
                      treatment modalities to target cancer cells, but they
                      frequently cause damage to the normal tissue, potentially
                      leading to side effects. As proton beam radiotherapy (PBT)
                      can precisely spare normal tissue, this therapeutic option
                      is of increasing importance regarding (neo-)adjuvant and
                      definitive anti-cancer therapies. Akin to photon-based
                      radiotherapy, PBT is often combined with systemic treatment,
                      such as doxorubicin (Dox). This study compares the cellular
                      response of human microvascular endothelial cells (HMEC-1)
                      following irradiation with photons (X) or protons (H) alone
                      and also in combination with different sequences of Dox. The
                      cellular survival, cell cycle, apoptosis, proliferation,
                      viability, morphology, and migration were all investigated.
                      Dox monotreatment had minor effects on all endpoints. Both
                      radiation qualities alone and in combination with longer Dox
                      schedules significantly reduced clonogenic survival and
                      proliferation, increased the apoptotic cell fraction,
                      induced a longer G2/M cell cycle arrest, and altered the
                      cell morphology towards
                      endothelial-to-mesenchymal-transition (EndoMT) processes.
                      Radiation quality effects were seen for metabolic viability,
                      proliferation, and motility of HMEC-1 cells. Additive
                      effects were found for longer Dox schedules. Overall,
                      similar effects were found for H/H-Dox and X/X-Dox.
                      Significant alterations between the radiation qualities
                      indicate different but not worse endothelial cell damage by
                      H/H-Dox.},
      keywords     = {Humans / Endothelial Cells / Protons / Photons /
                      Doxorubicin: pharmacology / G2 Phase Cell Cycle Checkpoints
                      / additive effects (Other) / cell survival (Other) /
                      combined treatment (Other) / doxorubicin (Other) /
                      endothelial cells (Other) / migration (Other) /
                      proliferation (Other) / proton beam radiotherapy (Other) /
                      Protons (NLM Chemicals) / Doxorubicin (NLM Chemicals)},
      cin          = {ED01},
      ddc          = {540},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37629014},
      pmc          = {pmc:PMC10454477},
      doi          = {10.3390/ijms241612833},
      url          = {https://inrepo02.dkfz.de/record/282351},
}