@article{WilbertGuckenbergerPolatetal.2010,
  author    = {Wilbert, Juergen and Guckenberger, Matthias and Polat, Buelent and Sauer, Otto and Vogele, Michael and Flentje, Michael and Sweeney, Reinhart A.},
  title     = {Semi-robotic 6 degree of freedom positioning for intracranial high precision radiotherapy; first phantom and clinical results},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68613},
  year      = {2010},
  abstract  = {Background: To introduce a novel method of patient positioning for high precision intracranial radiotherapy. Methods: An infrared(IR)-array, reproducibly attached to the patient via a vacuum-mouthpiece(vMP) and connected to the table via a 6 degree-of-freedom(DoF) mechanical arm serves as positioning and fixation system. After IR-based manual prepositioning to rough treatment position and fixation of the mechanical arm, a cone-beam CT(CBCT) is performed. A robotic 6 DoF treatment couch (HexaPOD™) then automatically corrects all remaining translations and rotations. This absolute position of infrared markers at the first fraction acts as reference for the following fractions where patients are manually prepositioned to within ± 2 mm and ± 2° of this IR reference position prior to final HexaPOD-based correction; consequently CBCT imaging is only required once at the first treatment fraction. The preclinical feasibility and attainable repositioning accuracy of this method was evaluated on a phantom and human volunteers as was the clinical efficacy on 7 pilot study patients. Results: Phantom and volunteer manual IR-based prepositioning to within ± 2 mm and ± 2° in 6DoF was possible within a mean(± SD) of 90 ± 31 and 56 ± 22 seconds respectively. Mean phantom translational and rotational precision after 6 DoF corrections by the HexaPOD was 0.2 ± 0.2 mm and 0.7 ± 0.8° respectively. For the actual patient collective, the mean 3D vector for inter-treatment repositioning accuracy (n = 102) was 1.6 ± 0.8 mm while intra-fraction movement (n = 110) was 0.6 ± 0.4 mm. Conclusions: This novel semi-automatic 6DoF IR-based system has been shown to compare favourably with existing non-invasive intracranial repeat fixation systems with respect to handling, reproducibility and, more importantly, intrafraction rigidity. Some advantages are full cranial positioning flexibility for single and fractionated IGRT treatments and possibly increased patient comfort.},
  subject      = {Strahlentherapie},
  language  = {en}
}
@article{SaidPolatSteinetal.2012,
  author    = {Said, Harun M. and Polat, Buelent and Stein, Susanne and Guckenberger, Mathias and Hagemann, Carsten and Staab, Adrian and Katzer, Astrid and Anacker, Jelena and Flentje, Michael and Vordermark, Dirk},
  title     = {Inhibition of N-Myc down regulated gene 1 in in vitro cultured human glioblastoma cells},
  series = {World Journal of Clinical Oncology},
  volume    = {3},
  journal   = {World Journal of Clinical Oncology},
  number    = {7},
  doi       = {10.5306/wjco.v3.i7.104},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123385},
  pages     = {104-110},
  year      = {2012},
  abstract  = {AIM: To study short dsRNA oligonucleotides (siRNA) as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1 (NDRG1) gene induced under different physiological conditions (Normoxia and hypoxia) modulating NDRG1 transcription, mRNA stability and translation. METHODS: A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 x 10(7) cells, nuclear extracts were prepared according to previous protocols. The pSUPER-NDRG1 vectors were designed, two sequences were selected from the human NDRG1 cDNA (5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on -actin and hypoxia-inducible factor (HIF)-1 mRNA sequences in GenBank. NDRG1 mRNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia (P < 0.05 was considered significant). RESULTS: siRNA- and iodoacetate (IAA)-mediated downregulation of NDRG1 mRNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results. CONCLUSION: NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it can represent a potential target for tumor treatment in human glioblastoma. The siRNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays.},
  language  = {en}
}
@article{WohllebenScherzadGuettleretal.2015,
  author    = {Wohlleben, Gisela and Scherzad, Agmal and G{\"u}ttler, Antje and Vordermark, Dirk and Kuger, Sebastian and Flentje, Michael and Polat, Buelent},
  title     = {Influence of hypoxia and irradiation on osteopontin expression in head and neck cancer and glioblastoma cell lines},
  series = {Radiation Oncology},
  volume    = {10},
  journal   = {Radiation Oncology},
  number    = {167},
  doi       = {10.1186/s13014-015-0473-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125746},
  year      = {2015},
  abstract  = {Background Tumor hypoxia is a known risk factor for reduced response to radiotherapy. The evaluation of noninvasive methods for the detection of hypoxia is therefore of interest. Osteopontin (OPN) has been discussed as an endogenous hypoxia biomarker. It is overexpressed in many cancers and is involved in tumor progression and metastasis. Methods To examine the influence of hypoxia and irradiation on osteopontin expression we used different cell lines (head and neck cancer (Cal27 and FaDu) and glioblastoma multiforme (U251 and U87)). Cells were treated with hypoxia for 24 h and were then irradiated with doses of 2 and 8 Gy. Osteopontin expression was analyzed on mRNA level by quantitative real-time RT-PCR (qPCR) and on protein level by western blot. Cell culture supernatants were evaluated for secreted OPN by ELISA. Results Hypoxia caused an increase in osteopontin protein expression in all cell lines. In Cal27 a corresponding increase in OPN mRNA expression was observed. In contrast the other cell lines showed a reduced mRNA expression under hypoxic conditions. After irradiation OPN mRNA expression raised slightly in FaDu and U87 cells while it was reduced in U251 and stable in Cal27 cells under normoxia. The combined treatment (hypoxia and irradiation) led to a slight increase of OPN mRNA after 2 Gy in U251 (24 h) and in U87 (24 and 48 h) cell lines falling back to base line after 8 Gy. This effect was not seen in Cal27 or in FaDu cells. Secreted OPN was detected only in the two glioblastoma cell lines with reduced protein levels under hypoxic conditions. Again the combined treatment resulted in a minor increase in OPN secretion 48 hours after irradiation with 8 Gy. Conclusion Osteopontin expression is strongly modulated by hypoxia and only to a minor extent by irradiation. Intracellular OPN homeostasis seems to vary considerably between cell lines. This may explain the partly conflicting results concerning response prediction and prognosis in the clinical setting.},
  language  = {en}
}