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@ARTICLE{Lacroix:136755,
      author       = {J. A. D. Lacroix$^*$ and Z. Kis$^*$ and R. Josupeit$^*$ and
                      F. Schlund$^*$ and A. Stroh-Dege$^*$ and M. Frank-Stöhr$^*$
                      and B. Leuchs$^*$ and J. R. Schlehofer$^*$ and J.
                      Rommelaere$^*$ and C. Dinsart$^*$},
      title        = {{P}reclinical {T}esting of an {O}ncolytic {P}arvovirus in
                      {E}wing {S}arcoma: {P}rotoparvovirus {H}-1 {I}nduces
                      {A}poptosis and {L}ytic {I}nfection {I}n {V}itro but {F}ails
                      to {I}mprove {S}urvival {I}n {V}ivo.},
      journal      = {Viruses},
      volume       = {10},
      number       = {6},
      issn         = {1999-4915},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2018-01193},
      pages        = {302},
      year         = {2018},
      abstract     = {About $70\%$ of all Ewing sarcoma (EWS) patients are
                      diagnosed under the age of 20 years. Over the last decades
                      little progress has been made towards finding effective
                      treatment approaches for primarily metastasized or
                      refractory Ewing sarcoma in young patients. Here, in the
                      context of the search for novel therapeutic options, the
                      potential of oncolytic protoparvovirus H-1 (H-1PV) to treat
                      Ewing sarcoma was evaluated, its safety having been proven
                      previously tested in adult cancer patients and its oncolytic
                      efficacy demonstrated on osteosarcoma cell cultures. The
                      effects of viral infection were tested in vitro on four
                      human Ewing sarcoma cell lines. Notably evaluated were
                      effects of the virus on the cell cycle and its replication
                      efficiency. Within 24 h after infection, the synthesis of
                      viral proteins was induced. Efficient H-1PV replication was
                      confirmed in all four Ewing sarcoma cell lines. The
                      cytotoxicity of the virus was determined on the basis of
                      cytopathic effects, cell viability, and cell lysis. These in
                      vitro experiments revealed efficient killing of Ewing
                      sarcoma cells by H-1PV at a multiplicity of infection
                      between 0.1 and 5 plaque forming units (PFU)/cell. In two of
                      the four tested cell lines, significant induction of
                      apoptosis by H-1PV was observed. H-1PV thus meets all the in
                      vitro criteria for a virus to be oncolytic towards Ewing
                      sarcoma. In the first xenograft experiments, however,
                      although an antiproliferative effect of intratumoral H-1PV
                      injection was observed, no significant improvement of animal
                      survival was noted. Future projects aiming to validate
                      parvovirotherapy for the treatment of pediatric Ewing
                      sarcoma should focus on combinatorial treatments and will
                      require the use of patient-derived xenografts and
                      immunocompetent syngeneic animal models.},
      cin          = {F010 / F170},
      ddc          = {610},
      cid          = {I:(DE-He78)F010-20160331 / I:(DE-He78)F170-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29865280},
      pmc          = {pmc:PMC6024310},
      doi          = {10.3390/v10060302},
      url          = {https://inrepo02.dkfz.de/record/136755},
}