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@ARTICLE{Bernardo:277805,
      author       = {T. Bernardo and C. Behrends and D. Klein and A. Kuntze and
                      B. Timmermann$^*$ and C. von Neubeck},
      title        = {{S}imilar additive effects of doxorubicin in combination
                      with photon or proton irradiation in soft tissue sarcoma
                      models.},
      journal      = {Frontiers in oncology},
      volume       = {13},
      issn         = {2234-943X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-01516},
      pages        = {1211984},
      year         = {2023},
      abstract     = {High-precision radiotherapy with proton beams is frequently
                      used in the management of aggressive soft tissue sarcoma
                      (STS) and is often combined with doxorubicin (Dox), the
                      first-line chemotherapy for STS. However, current treatment
                      approaches continue to result in high local recurrence rates
                      often occurring within the treatment field. This strongly
                      indicates the need of optimized treatment protocols taking
                      the vast heterogeneity of STS into account, thereby
                      fostering personalized treatment approaches. Here, we used
                      preclinical STS models to investigate the radiation response
                      following photon (X) or proton (H) irradiation alone and in
                      combination with different treatment schedules of Dox. As
                      preclinical models, fibrosarcoma (HT-1080), undifferentiated
                      pleiomorphic sarcoma (GCT), and embryonal rhabdomyosarcoma
                      (RD) cell lines were used; the latter two are mutated for
                      TP53. The cellular response regarding clonogenic survival,
                      apoptosis, cell-cycle distribution, proliferation,
                      viability, morphology, and motility was investigated. The
                      different STS cell types revealed a dose-dependent radiation
                      response with reduced survival, proliferation, viability,
                      and motility whereas G2/M phase arrest as well as apoptosis
                      were induced. RD cells showed the most radiosensitive
                      phenotype; the linear quadratic model fit could not be
                      applied. In combined treatment schedules, Dox showed the
                      highest efficiency when applied after or before and after
                      radiation; Dox treatment only before radiation was less
                      efficient. GCT cells were the most chemoresistant cell line
                      in this study most probably due to their TP53 mutation
                      status. Interestingly, similar additive effects could be
                      observed for X or H irradiation in combination with Dox
                      treatment. However, the additive effects were determined
                      more frequently for X than for H irradiation. Thus, further
                      investigations are needed to specify alternative drug
                      therapies that display superior efficacy when combined with
                      H therapy.},
      keywords     = {additive effect (Other) / combined treatment (Other) /
                      doxorubicin (Other) / proton beam radiotherapy (Other) /
                      soft tissue sarcoma (Other)},
      cin          = {ED01},
      ddc          = {610},
      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:37503316},
      pmc          = {pmc:PMC10368985},
      doi          = {10.3389/fonc.2023.1211984},
      url          = {https://inrepo02.dkfz.de/record/277805},
}