@article{DjuzenovaMemmelSukhorukovetal.2014,
  author    = {Djuzenova, Cholpon S. and Memmel, Simon and Sukhorukov, Vladimir L. and H{\"o}ring, Marcus and Westerling, Katherine and Fiedler, Vanessa and Katzer, Astrid and Krohne, Georg and Flentje, Michael},
  title     = {Cell Surface Area and Membrane Folding in Glioblastoma Cell Lines Differing in PTEN and p53 Status},
  doi       = {10.1371/journal.pone.0087052},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111322},
  year      = {2014},
  abstract  = {Glioblastoma multiforme (GBM) is characterized by rapid growth, invasion and resistance to chemo-/radiotherapy. The complex cell surface morphology with abundant membrane folds, microvilli, filopodia and other membrane extensions is believed to contribute to the highly invasive behavior and therapy resistance of GBM cells. The present study addresses the mechanisms leading to the excessive cell membrane area in five GBM lines differing in mutational status for PTEN and p53. In addition to scanning electron microscopy (SEM), the membrane area and folding were quantified by dielectric measurements of membrane capacitance using the single-cell electrorotation (ROT) technique. The osmotic stability and volume regulation of GBM cells were analyzed by video microscopy. The expression of PTEN, p53, mTOR and several other marker proteins involved in cell growth and membrane synthesis were examined by Western blotting. The combined SEM, ROT and osmotic data provided independent lines of evidence for a large variability in membrane area and folding among tested GBM lines. Thus, DK-MG cells (wild type p53 and wild type PTEN) exhibited the lowest degree of membrane folding, probed by the area-specific capacitance Cm = 1.9 µF/cm2. In contrast, cell lines carrying mutations in both p53 and PTEN (U373-MG and SNB19) showed the highest Cm values of 3.7-4.0 µF/cm2, which corroborate well with their heavily villated cell surface revealed by SEM. Since PTEN and p53 are well-known inhibitors of mTOR, the increased membrane area/folding in mutant GBM lines may be related to the enhanced protein and lipid synthesis due to a deregulation of the mTOR-dependent downstream signaling pathway. Given that membrane folds and extensions are implicated in tumor cell motility and metastasis, the dielectric approach presented here provides a rapid and simple tool for screening the biophysical cell properties in studies on targeting chemo- or radiotherapeutically the migration and invasion of GBM and other tumor types.},
  language  = {en}
}
@article{WiegeringIsbertDietzetal.2014,
  author    = {Wiegering, Armin and Isbert, Christoph and Dietz, Ulrich A. and Kunzmann, Volker and Ackermann, Sabine and Kerscher, Alexander and Maeder, Uwe and Flentje, Michael and Schlegel, Nicolas and Reibetanz, Joachim and Germer, Christoph-Thomas and Klein, Ingo},
  title     = {Multimodal therapy in treatment of rectal cancer is associated with improved survival and reduced local recurrence - a retrospective analysis over two decades},
  doi       = {10.1186/1471-2407-14-816},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110606},
  year      = {2014},
  abstract  = {Background The management of rectal cancer (RC) has substantially changed over the last decades with the implementation of neoadjuvant chemoradiotherapy, adjuvant therapy and improved surgery such as total mesorectal excision (TME). It remains unclear in which way these approaches overall influenced the rate of local recurrence and overall survival. Methods Clinical, histological and survival data of 658 out of 662 consecutive patients with RC were analyzed for treatment and prognostic factors from a prospectively expanded single-institutional database. Findings were then stratified according to time of diagnosis in patient groups treated between 1993 and 2001 and 2002 and 2010. Results The study population included 658 consecutive patients with rectal cancer between 1993 and 2010. Follow up data was available for 99.6\% of all 662 treated patients. During the time period between 2002 and 2010 significantly more patients underwent neoadjuvant chemoradiotherapy (17.6\% vs. 60\%) and adjuvant chemotherapy (37.9\% vs. 58.4\%). Also, the rate of reported TME during surgery increased. The rate of local or distant metastasis decreased over time, and tumor related 5-year survival increased significantly with from 60\% to 79\%. Conclusion In our study population, the implementation of treatment changes over the last decade improved the patient's outcome significantly. Improvements were most evident for UICC stage III rectal cancer.},
  language  = {en}
}