@article{FeldheimKesslerSchmittetal.2018, author = {Feldheim, Jonas and Kessler, Almuth F and Schmitt, Dominik and Wilczek, Lara and Linsenmann, Thomas and Dahlmann, Mathias and Monoranu, Camelia M and Ernestus, Ralf-Ingo and Hagemann, Carsten and L{\"o}hr, Mario}, title = {Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients}, series = {OncoTargets and Therapy}, volume = {11}, journal = {OncoTargets and Therapy}, doi = {10.2147/OTT.S176549}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177541}, pages = {8673-8684}, year = {2018}, abstract = {Background: ATF5 suppresses differentiation of neuroprogenitor cells and is overexpressed in glioblastoma (GBM). A reduction of its expression leads to apoptotic GBM cell death. Data on ATF5 expression in astrocytoma WHO grade II (low-grade astrocytoma [LGA]) are scarce and lacking on recurrent GBM. Patients and methods: ATF5 mRNA was extracted from frozen samples of patients' GBM (n=79), LGA (n=40), and normal brain (NB, n=10), quantified by duplex qPCR and correlated with retrospectively collected clinical data. ATF5 protein expression was evaluated by measuring staining intensity on immunohistochemistry. Results: ATF5 mRNA was overexpressed in LGA (sevenfold, P<0.001) and GBM (tenfold, P<0.001) compared to NB, which was confirmed on protein level. Although ATF5 mRNA expression in GBM showed a considerable fluctuation range, groups of varying biological behavior, that is, local/multifocal growth or primary tumor/relapse and the tumor localization at diagnosis, were not significantly different. ATF5 mRNA correlated with the patients' age (r=0.339, P=0.028) and inversely with Ki67-staining (r=-0.421, P=0.007). GBM patients were allocated to a low and a high ATF5 expression group by the median ATF5 overexpression compared to NB. Kaplan-Meier analysis and Cox regression indicated that ATF5 mRNA expression significantly correlated with short-term survival (t<12 months, median survival 18 vs 13 months, P=0.022, HR 2.827) and progression-free survival (PFS) (12 vs 6 months, P=0.024). This advantage vanished after 24 months (P=0.084). Conclusion: ATF5 mRNA expression could be identified as an additional, though not independent factor correlating with overall survival and PFS. Since its inhibition might lead to the selective death of glioma cells, it might serve as a potential ubiquitous therapeutic target in astrocytic tumors.}, language = {en} } @article{LinsenmannMonoranuKessleretal.2013, author = {Linsenmann, Thomas and Monoranu, Camelia M. and Kessler, Almuth F. and Ernestus, Ralf I. and Westermaier, Thomas}, title = {Bone chips, fibrin glue, and osteogeneration following lateral suboccipital craniectomy: a case report}, series = {BMC Research Notes}, journal = {BMC Research Notes}, doi = {10.1186/1756-0500-6-523}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97346}, year = {2013}, abstract = {Background Suboccipital craniectomy is a conventional approach for exploring cerebellopontine angle lesions. A variety of techniques have been successfully employed to reconstruct a craniectomy. This is the first report about the histological findings after performing a cranioplasty by using a mixture of autologous bone chips and human allogenic fibrin glue. Case presentation A 53-year-old German woman underwent left lateral suboccipital retrosigmoidal craniectomy for treatment of trigeminal neuralgia in 2008. Cranioplasty was perfomed by using a mixture of autologous bone chips and human allogenic fibrin glue. Due to recurrent neuralgia, a second left lateral suboccipital craniectomy was performed in 2012. The intraoperative findings revealed a complete ossification of the former craniotomy including widely mature trabecular bone tissue in the histological examination. Conclusion A mixture of autologous bone chips and human allogenic fibrin glue seems to provide sufficient bone-regeneration revealed by histological and neuroradiological examinations.}, 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{LapaLueckerathKleinleinetal.2016, author = {Lapa, Constantin and L{\"u}ckerath, Katharina and Kleinlein, Irene and Monoranu, Camelia Maria and Linsenmann, Thomas and Kessler, Almuth F. and Rudelius, Martina and Kropf, Saskia and Buck, Andreas K. and Ernestus, Ralf-Ingo and Wester, Hans-J{\"u}rgen and L{\"o}hr, Mario and Herrmann, Ken}, title = {\(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma}, series = {Theranostics}, volume = {6}, journal = {Theranostics}, number = {3}, doi = {10.7150/thno.13986}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168174}, pages = {428-434}, year = {2016}, abstract = {Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. \(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.}, language = {en} } @article{LoehrKesslerMonoranuetal.2019, author = {L{\"o}hr, Mario and Kessler, Almuth F. and Monoranu, Camelia-Maria and Grosche, Jens and Linsenmann, Thomas and Ernestus, Ralf-Ingo and H{\"a}rtig, Wolfgang}, title = {Primary brain amyloidoma, both a neoplastic and a neurodegenerative disease: a case report}, series = {BMC Neurology}, volume = {19}, journal = {BMC Neurology}, doi = {10.1186/s12883-019-1274-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200341}, pages = {59}, year = {2019}, abstract = {Background Scattered extracellular deposits of amyloid within the brain parenchyma can be found in a heterogeneous group of diseases. Its condensed accumulation in the white matter without evidence for systemic amyloidosis is known as primary brain amyloidoma (PBA). Although originally considered as a tumor-like lesion by its space-occupying effect, this condition displays also common hallmarks of a neurodegenerative disorder. Case presentation A 50-year-old woman presented with a mild cognitive decline and seizures with a right temporal, irregular and contrast-enhancing mass on magnetic resonance imaging. Suspecting a high-grade glioma, the firm tumor was subtotally resected. Neuropathological examination showed no glioma, but distinct features of a neurodegenerative disorder. The lesion was composed of amyloid AL λ aggregating within the brain parenchyma as well as the adjacent vessels, partially obstructing the vascular lumina. Immunostaining confirmed a distinct perivascular inflammatory reaction. After removal of the PBA, mnestic impairments improved considerably, the clinical course and MRI-results are stable in the 8-year follow-up. Conclusion Based on our histopathological findings, we propose to regard the clinicopathological entity of PBA as an overlap between a neoplastic and neurodegenerative disorder. Since the lesions are locally restricted, they might be amenable to surgery with the prospect of a definite cure.}, language = {en} } @article{HagemannNeuhausDahlmannetal.2019, author = {Hagemann, Carsten and Neuhaus, Nikolas and Dahlmann, Mathias and Kessler, Almuth F. and Kobelt, Dennis and Herrmann, Pia and Eyrich, Matthias and Freitag, Benjamin and Linsenmann, Thomas and Monoranu, Camelia M. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Stein, Ulrike}, title = {Circulating MACC1 transcripts in glioblastoma patients predict prognosis and treatment response}, series = {Cancers}, volume = {11}, journal = {Cancers}, number = {6}, issn = {2072-6694}, doi = {10.3390/cancers11060825}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197327}, year = {2019}, abstract = {Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacksreliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associatedin colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinicaloutcome and therapy response in glioblastomas. MACC1 transcripts were significantly higher inpatients compared to controls. Low MACC1 levels clustered together with other prognosticallyfavorable markers. It was associated with patients' prognosis in conjunction with the isocitratedehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable(median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (medianOS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months).No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levelsreceiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1levels (median OS 8.1 months). Patients not receiving the standard regimen showed the worstprognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulatingMACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcomeprediction and help define more precise risk categories of glioblastoma patients.}, language = {en} }