@article{PickhardSieglBaumannetal.2014,
  author    = {Pickhard, Anja and Siegl, Michael and Baumann, Alexander and Huhn, Maximilian and Wirth, Markus and Reiter, Rudolf and Rudelius, Martina and Piontek, Guido and Brockhoff, Gero},
  title     = {The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism},
  series = {Oncotarget},
  volume    = {5},
  journal   = {Oncotarget},
  number    = {14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120757},
  pages     = {5428-38},
  year      = {2014},
  abstract  = {Objectives: The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines. Materials and methods: First, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples. The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting. Results: Immunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27). Conclusion: This study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown.},
  language  = {en}
}
@article{SchieflerPiontekDoescheretal.2014,
  author    = {Schiefler, Carlotta and Piontek, Guido and Doescher, Johannes and Schuettler, Dominik and Mißlbeck, Martin and Rudelius, Martina and Haug, Anna and Reiter, Rudolf and Brockhoff, Gero and Pickhard, Anja},
  title     = {Inhibition of SphK1 reduces radiation-induced migration and enhances sensitivity to cetuximab treatment by affecting the EGFR/SphK1 crosstalk},
  series = {Oncotarget},
  volume    = {5},
  journal   = {Oncotarget},
  number    = {20},
  issn      = {1949-2553},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120929},
  pages     = {9877-9888},
  year      = {2014},
  abstract  = {SphK1 is known to play a role in tumor progression, resistance to radiochemotherapy, and migration patterns. As the overall survival rates of squamous cell carcinoma of the head and neck (HNSCC) remain poor due to limitations in surgery and irradiation and chemotherapy resistance, SphK1 is an important enzyme to investigate. The purpose of this study was to elucidate the impact of SphK1 on irradiation efficacy of HNSCC in-vitro with emphasis on EGFR signaling. By immunhistochemical staining we found a positive correlation between EGFR and SphK1 expression in patient specimens. In colony formation assays irradiation sensitive cell lines showed a poor response to cetuximab, an EGFR inhibitor, and SKI-II, a SphK1 inhibitor, and vice versa. In irradiation sensitive cells an enhanced reduction of cell migration and survival was found upon simultaneous targeting of EGFR and SphK1. In the present study, we elucidated a linkage between the two signaling pathways with regard to the efficacy of cetuximab treatment and the impact on the migration behavior of tumor cells. We investigated the biological impact of inhibiting these pathways and examined the biochemical implications after different treatments. An understanding of the processes involved could help to improve the treatment of patients with HNSCC.},
  language  = {en}
}