@article{HagemannKesslerWiesneretal.2014,
  author    = {Hagemann, Carsten and Kessler, Almuth Friederike and Wiesner, Miriam and Denner, Joachim and K{\"a}mmerer, Ulrike and Vince, Giles Hamilton and Linsenmann, Thomas and L{\"o}hr, Mario and Ernestus, Ralf-Ingo},
  title     = {Expression-analysis of the human endogenous retrovirus HERV-K in human astrocytic tumors},
  doi       = {10.1186/1756-0500-7-159},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110211},
  year      = {2014},
  abstract  = {Background The human endogenous retrovirus K (HERV-K) has been acquired by the genome of human ancestors million years ago. It is the most complete of the HERVs with transcriptionally active gag, pol and env genes. Splice variants of env, which are rec, 1.5 kb transcript and Np9 have been suggested to be tumorigenic. Transcripts of HERV-K have been detected in a multitude of human cancers. However, no such reports are available concerning glioblastomas (GBM), the most common malignant brain tumor in adults. Patients have a limited prognosis of 14.6 months in median, despite standard treatment. Therefore, we elucidated whether HERV-K transcripts could be detected in these tumors and serve as new molecular target for treatment. Findings We analyzed human GBM cell lines, tissue samples from patients and primary cell cultures of different passages for HERV-K full length mRNA and env, rec and 1.5 kb transcripts. While the GBM cell lines U138, U251, U343 and GaMG displayed weak and U87 strong expression of the full length HERV-K, the splice products could not be detected, despite a weak expression of env mRNA in U87 cells. Very few tissue samples from patients showed weak expression of env mRNA, but none of the rec or 1.5 kb transcripts. Primary cells expressed the 1.5 kb transcript weakly in early passages, but lost HERV-K expression with extended culture time. Conclusions These data suggest that HERV-K splice products do not play a role in human malignant gliomas and therefore, are not suitable as targets for new therapy regimen.},
  language  = {en}
}
@article{LinsenmannMonoranuVinceetal.2014,
  author    = {Linsenmann, Thomas and Monoranu, Camelia M. and Vince, Giles H. and Westermaier, Thomas and Hagemann, Carsten and Kessler, Almuth F. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario},
  title     = {Long-term tumor control of spinal dissemination of cerebellar glioblastoma multiforme by combined adjuvant bevacizumab antibody therapy: a case report},
  doi       = {10.1186/1756-0500-7-496},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110536},
  year      = {2014},
  abstract  = {Background Glioblastoma multiforme located in the posterior fossa is extremely rare with a frequency up to 3.4\%. Compared with glioblastoma of the hemispheres the prognosis of infratentorial glioblastoma seems to be slightly better. Absence of brainstem invasion and low expression rates of epidermal growth factor receptor are described as factors for long-time survival due to the higher radiosensitivity of these tumors. Case presentation In this case study, we report a German female patient with an exophytic glioblastoma multiforme arising from the cerebellar tonsil and a secondary spinal manifestation. Furthermore, the tumor showed no O (6)-Methylguanine-DNA methyltransferase promotor-hypermethylation and no isocitrate dehydrogenase 1 mutations. All these signs are accompanied by significantly shorter median overall survival. A long-term tumor control of the spinal metastases was achieved by a combined temozolomide/bevacizumab and irradiation therapy, as part of a standard care administered by the treating physician team. Conclusion To our knowledge this is the first published case of a combined cerebellar exophytic glioblastoma with a subsequent solid spinal manifestation. Furthermore this case demonstrates a benefit undergoing this special adjuvant therapy regime in terms of overall survival. Due to the limited overall prognosis of the disease, spinal manifestations of glioma are rarely clinically relevant. The results of our instructive case, however, with a positive effect on both life quality and survival warrant treating future patients in the frame of a prospective clinical study.},
  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{HagemannAnackerErnestusetal.2012,
  author    = {Hagemann, Carsten and Anacker, Jelena and Ernestus, Ralf-Ingo and Vince, Giles H.},
  title     = {A complete compilation of matrix metalloproteinase expression in human malignant gliomas},
  series = {World Journal of Clinical Oncology},
  volume    = {3},
  journal   = {World Journal of Clinical Oncology},
  number    = {5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123982},
  pages     = {67-79},
  year      = {2012},
  abstract  = {Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases (MMPs) were found in glioblastoma (GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma (LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory data available. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.},
  language  = {en}
}
@article{HagemannAnackerHaasetal.2010,
  author    = {Hagemann, Carsten and Anacker, Jelena and Haas, Stefanie and Riesner, Daniela and Sch{\"o}mig, Beate and Ernestus, Ralf-Ingo and Vince, Giles H.},
  title     = {Comparative expression pattern of Matrix-Metalloproteinases in human glioblastoma cell-lines and primary cultures},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67980},
  year      = {2010},
  abstract  = {Background: Glioblastomas (GBM), the most frequent malignant brain tumors in adults, are characterized by an aggressive local growth pattern and highly invasive tumor cells. This invasion is facilitated by expression of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases. They mediate the degradation of protein components of the extracellular matrix. Twenty-three family members are known. Elevated levels of several of them have been reported in GBM. GBM cell-lines are used for in vitro studies of cell migration and invasion. Therefore, it is essential to know their MMP expression patterns. Only limited data for some of the cell-lines are published, yet. To fill the gaps in our knowledge would help to choose suitable model systems for analysis of regulation and function of MMPs during GBM tumorigenesis, cell migration and invasion. Findings: We analysed MMP-1, -8, -9, -10, -11, -13, -17, -19, -20, -21, -23, -24, -26, -27, and MMP-28 expression in seven GBM cell-lines (SNB-19, GaMG, U251, U87, U373, U343, U138) and in four primary cell cultures by semiquantitative RT-PCR, followed changes in the MMP expression pattern with increasing passages of cell culture and examined the influence of TNF-a and TGF-b1 stimulation on the expression of selected MMPs in U251 and U373 cells. MMP-13, -17, -19 and -24 were expressed by all analyzed cell-lines, whereas MMP-20 and MMP-21 were not expressed by any of them. The other MMPs showed variable expression, which was dependent on passage number. Primary cells displayed a similar MMP-expression pattern as the cell-lines. In U251 and U373 cells expression of MMP-9 and MMP-19 was stimulated by TNF-a. MMP-1 mRNA expression was significantly increased in U373 cells, but not in U251 cells by this cytokine. Whereas TGF-b1 had no impact on MMP expression in U251 cells, it significantly induced MMP-11 and MMP-24 expression in U373 cells. Conclusions: Literature-data and our own results suggest that the expression pattern of MMPs is highly variable, dependent on the cell-line and the cell-culture conditions used and that also regulation of MMP expression by cytokines is cell-line dependent. This is of high impact for the transfer of cell-culture experiments to clinical implementation.},
  subject      = {Metalloproteinasen},
  language  = {en}
}