@article{LapaLinsenmannLueckerathetal.2015,
  author    = {Lapa, Constantin and Linsenmann, Thomas and L{\"u}ckerath, Katharina and Samnick, Samuel and Herrmann, Ken and Stoffer, Carolin and Ernestus, Ralf-Ingo and Buck, Andreas K. and L{\"o}hr, Mario and Monoranu, Camelia-Maria},
  title     = {Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy?},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {3},
  doi       = {10.1371/journal.pone.0122269},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125498},
  pages     = {e0122269},
  year      = {2015},
  abstract  = {Background Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM. Methods 15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using \(^{68}Ga-DOTATATE\) was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry. Results The amount of microglia/macrophages ranged from <10\% to >50\% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns. Conclusion SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.},
  language  = {en}
}
@article{FeldheimKesslerMonoranuetal.2019,
  author    = {Feldheim, Jonas and Kessler, Almuth F. and Monoranu, Camelia M. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten},
  title     = {Changes of O\(^6\)-Methylguanine DNA Methyltransferase (MGMT) promoter methylation in glioblastoma relapse—a meta-analysis type literature review},
  series = {Cancers},
  volume    = {11},
  journal   = {Cancers},
  number    = {12},
  issn      = {2072-6694},
  doi       = {10.3390/cancers11121837},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193040},
  year      = {2019},
  abstract  = {Methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter has emerged as strong prognostic factor in the therapy of glioblastoma multiforme. It is associated with an improved response to chemotherapy with temozolomide and longer overall survival. MGMT promoter methylation has implications for the clinical course of patients. In recent years, there have been observations of patients changing their MGMT promoter methylation from primary tumor to relapse. Still, data on this topic are scarce. Studies often consist of only few patients and provide rather contrasting results, making it hard to draw a clear conclusion on clinical implications. Here, we summarize the previous publications on this topic, add new cases of changing MGMT status in relapse and finally combine all reports of more than ten patients in a statistical analysis based on the Wilson score interval. MGMT promoter methylation changes are seen in 115 of 476 analyzed patients (24\%; CI: 0.21-0.28). We discuss potential reasons like technical issues, intratumoral heterogeneity and selective pressure of therapy. The clinical implications are still ambiguous and do not yet support a change in clinical practice. However, retesting MGMT methylation might be useful for future treatment decisions and we encourage clinical studies to address this topic},
  language  = {en}
}