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@ARTICLE{Wyrich:282680,
      author       = {M. Wyrich and H. Ohlig and M. Wessolly$^*$ and E. Mairinger
                      and J. Steinborn and L. Brcic and B. Hegedus and T. Hager
                      and K. Greimelmaier and J. Wohlschlaeger and F.
                      Mairinger$^*$ and S. Borchert$^*$},
      title        = {{I}nduction of metallothionein expression by
                      supplementation of zinc induces resistance against
                      platinum-based treatment in malignant pleural mesothelioma},
      journal      = {Translational cancer research},
      volume       = {12},
      number       = {8},
      issn         = {2218-676X},
      address      = {Shatin},
      publisher    = {AME Publishing Company},
      reportid     = {DKFZ-2023-01826},
      pages        = {1929 - 1936},
      year         = {2023},
      abstract     = {Background: Malignant pleural mesothelioma (MPM) is an
                      aggressive tumor with a dismal prognosis. Currently,
                      multimodality treatment including chemotherapy with
                      cisplatin or carboplatin in combination with pemetrexed
                      offers the best options. Detoxification of heavy metals in
                      the cell by metallothioneins (MT) is associated with early
                      failure to platin-based chemotherapy. The induction of MTs
                      gene expression or its enzyme results in saturation by
                      exposure to metal ions such as zinc or cadmium. Its
                      therapeutically effect is still not analyzed in depth.
                      Methods: In our study, we investigated three MPM cell lines
                      and one fibroblast cell line in the course of cisplatin
                      treatment and supplementation of zinc. Cell state analyses
                      via an enzyme-activity based assay were performed. With
                      this, we were able to analyze apoptosis, necrosis and
                      viability of cells. Additionally, we tested treated cells
                      for changes in metallothionein IIA (MT2A) expression by
                      using quantitative realtime polymerase chain reaction.
                      Results: Zinc supplementation induces gene expression of
                      MT2A. Overall, a zinc dose-dependent induction of apoptosis
                      under platin-based treatment could be observed. This effect
                      could be verified in all analyzed cell lines in varying
                      intensity. Conclusions: MT expression is induced by zinc in
                      a dose-dependent manner and inhibits a successful cisplatin
                      therapy. Therefore, heavy metal exposure during cisplatin
                      therapy, e.g., via cigarette smoke, might be an important
                      factor. This should be considered in further therapeutic
                      approaches.},
      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},
      doi          = {10.21037/tcr-22-2651},
      url          = {https://inrepo02.dkfz.de/record/282680},
}