@article{GereckeSchumacherBerndzenetal.2019,
  author    = {Gerecke, Christian and Schumacher, Fabian and Berndzen, Alide and Homann, Thomas and Kleuser, Burkhard},
  title     = {Vitamin C in combination with inhibition of mutant IDH1 synergistically activates TET enzymes and epigenetically modulates gene silencing in colon cancer cells},
  series = {Epigenetics : the official journal of the DNA Methylation Society},
  volume    = {15},
  journal   = {Epigenetics : the official journal of the DNA Methylation Society},
  number    = {3},
  publisher = {Taylor \& Francis Group},
  address   = {Philadelphia},
  issn      = {1559-2294},
  doi       = {10.1080/15592294.2019.1666652},
  pages     = {307 -- 322},
  year      = {2019},
  abstract  = {Mutations in the enzyme isocitrate dehydrogenase 1 (IDH1) lead to metabolic alterations and a sustained formation of 2-hydroxyglutarate (2-HG). 2-HG is an oncometabolite as it inhibits the activity of alpha-ketoglutarate-dependent dioxygenases such as ten-eleven translocation (TET) enzymes. Inhibitors of mutant IDH enzymes, like ML309, are currently tested in order to lower the levels of 2-HG. Vitamin C (VC) is an inducer of TET enzymes. To test a new therapeutic avenue of synergistic effects, the anti-neoplastic activity of inhibition of mutant IDH1 via ML309 in the presence of VC was investigated in the colon cancer cell line HCT116 IDH1(R132H/+) (harbouring a mutated IDH1 allele) and the parental cells HCT116 IDH1(+/+) (wild type IDH1). Measurement of the oncometabolite indicated a 56-fold higher content of 2-HG in mutated cells compared to wild type cells. A significant reduction of 2-HG was observed in mutated cells after treatment with ML 309, whereas VC produced only minimally changes of the oncometabolite. However, combinatorial treatment with both, ML309 and VC, in mutated cells induced pronounced reduction of 2-HG leading to levels comparable to those in wild type cells. The decreased level of 2-HG in mutated cells after combinatorial treatment was accompanied by an enhanced global DNA hydroxymethylation and an increased gene expression of certain tumour suppressors. Moreover, mutated cells showed an increased percentage of apoptotic cells after treatment with non-cytotoxic concentrations of ML309 and VC. These results suggest that combinatorial therapy is of interest for further investigation to rescue TET activity and treatment of IDH1/2 mutated cancers.},
  language  = {en}
}
@article{WirschingGrassmannEichelmannetal.2018,
  author    = {Wirsching, Jan and Grassmann, Sophie and Eichelmann, Fabian and Harms, Laura Malin and Schenk, Matthew and Barth, Eva and Berndzen, Alide and Olalekan, Moses and Sarmini, Leen and Zuberer, Hedwig and Aleksandrova, Krasimira},
  title     = {Development and reliability assessment of a new quality appraisal tool for cross-sectional studies using biomarker data (BIOCROSS)},
  series = {BMC Medical Research Methodology},
  volume    = {18},
  journal   = {BMC Medical Research Methodology},
  publisher = {BMC},
  address   = {London},
  issn      = {1471-2288},
  doi       = {10.1186/s12874-018-0583-x},
  pages     = {8},
  year      = {2018},
  abstract  = {Background Biomarker-based analyses are commonly reported in observational epidemiological studies; however currently there are no specific study quality assessment tools to assist evaluation of conducted research. Accounting for study design and biomarker measurement would be important for deriving valid conclusions when conducting systematic data evaluation. Methods We developed a study quality assessment tool designed specifically to assess biomarker-based cross-sectional studies (BIOCROSS) and evaluated its inter-rater reliability. The tool includes 10-items covering 5 domains: 'Study rational', 'Design/Methods', 'Data analysis', 'Data interpretation' and 'Biomarker measurement', aiming to assess different quality features of biomarker cross-sectional studies. To evaluate the inter-rater reliability, 30 studies were distributed among 5 raters and intraclass correlation coefficients (ICC-s) were derived from respective ratings. Results The estimated overall ICC between the 5 raters was 0.57 (95\% Confidence Interval (CI): 0.38-0.74) indicating a good inter-rater reliability. The ICC-s ranged from 0.11 (95\% CI: 0.01-0.27) for the domain 'Study rational' to 0.56 (95\% CI: 0.40-0.72) for the domain 'Data interpretation'. Conclusion BIOCROSS is a new study quality assessment tool suitable for evaluation of reporting quality from cross-sectional epidemiological studies employing biomarker data. The tool proved to be reliable for use by biomedical scientists with diverse backgrounds and could facilitate comprehensive review of biomarker studies in human research.},
  language  = {en}
}