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@ARTICLE{Kreycy:124289,
      author       = {N. Kreycy and C. Gotzian and T. Fleming and C.
                      Flechtenmacher and N. Grabe and P. Plinkert and J. Hess$^*$
                      and K. Zaoui},
      title        = {{G}lyoxalase 1 expression is associated with an unfavorable
                      prognosis of oropharyngeal squamous cell carcinoma.},
      journal      = {BMC cancer},
      volume       = {17},
      number       = {1},
      issn         = {1471-2407},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2017-01185},
      pages        = {382},
      year         = {2017},
      abstract     = {Glyoxalase 1 is a key enzyme in the detoxification of
                      reactive metabolites such as methylglyoxal and induced
                      Glyoxalase 1 expression has been demonstrated for several
                      human malignancies. However, the regulation and clinical
                      relevance of Glyoxalase 1 in the context of head and neck
                      squamous cell carcinoma has not been addressed so
                      far.Argpyrimidine modification as a surrogate for
                      methylglyoxal accumulation and Glyoxalase 1 expression in
                      tumor cells was assessed by immunohistochemical staining of
                      tissue microarrays with specimens from oropharyngeal
                      squamous cell carcinoma patients (n = 154). Prognostic
                      values of distinct Glyoxalase 1 staining patterns were
                      demonstrated by Kaplan-Meier, univariate and multivariate
                      Cox proportional hazard model analysis. The impact of
                      exogenous methylglyoxal or a Glyoxalase 1 inhibitor on the
                      viability of two established tumor cell lines was monitored
                      by a colony-forming assay in vitro.Glyoxalase 1 expression
                      in tumor cells of oropharyngeal squamous cell carcinoma
                      patients was positively correlated with the presence of
                      Argpyrimidine modification and administration of exogenous
                      methylglyoxal induced Glyoxalase 1 protein levels in FaDu
                      and Cal27 cells in vitro. Cal27 cells with lower basal and
                      methylglyoxal-induced Glyoxalase 1 expression were more
                      sensitive to the cytotoxic effect at high methylgyoxal
                      concentrations and both cell lines showed a decrease in
                      colony formation with increasing amounts of a Glyoxalase 1
                      inhibitor. A high and nuclear Glyoxalase 1 staining was
                      significantly correlated with shorter progression-free and
                      disease-specific survival, and served as an independent risk
                      factor for an unfavorable prognosis of oropharyngeal
                      squamous cell carcinoma patients.Induced Glyoxalase 1
                      expression is a common feature in the pathogenesis of
                      oropharyngeal squamous cell carcinoma and most likely
                      represents an adaptive response to the accumulation of
                      cytotoxic metabolites. Oropharyngeal squamous cell carcinoma
                      patients with a high and nuclear Glyoxalase 1 staining
                      pattern have a high risk for treatment failure, but might
                      benefit from pharmacological targeting Glyoxalase 1
                      activity.},
      cin          = {G405},
      ddc          = {610},
      cid          = {I:(DE-He78)G405-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28549423},
      pmc          = {pmc:PMC5446730},
      doi          = {10.1186/s12885-017-3367-5},
      url          = {https://inrepo02.dkfz.de/record/124289},
}