Bähr, Mathias

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical and Translational Medicine"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Caldi Gomes, Lucas"],["dc.contributor.author","Roser, Anna‐Elisa"],["dc.contributor.author","Jain, Gaurav"],["dc.contributor.author","Pena Centeno, Tonatiuh"],["dc.contributor.author","Maass, Fabian"],["dc.contributor.author","Schilde, Lukas"],["dc.contributor.author","May, Caroline"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2021-06-01T09:41:18Z"],["dc.date.available","2021-06-01T09:41:18Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1002/ctm2.357"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84876"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","2001-1326"],["dc.relation.issn","2001-1326"],["dc.title","MicroRNAs from extracellular vesicles as a signature for Parkinson's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1297"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","STEM CELLS"],["dc.bibliographiccitation.lastpage","1310"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Doeppner, T. R."],["dc.contributor.author","Ewert, T. A. S."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Herz, J."],["dc.contributor.author","Zechariah, A."],["dc.contributor.author","Elali, A."],["dc.contributor.author","Ludwig, A.-K."],["dc.contributor.author","Giebel, B."],["dc.contributor.author","Nagel, F."],["dc.contributor.author","Dietz, G. P. H."],["dc.contributor.author","Weise, J."],["dc.contributor.author","Hermann, D. M."],["dc.contributor.author","Bähr, M."],["dc.date.accessioned","2017-09-07T11:48:52Z"],["dc.date.available","2017-09-07T11:48:52Z"],["dc.date.issued","2012"],["dc.description.abstract","Novel therapeutic concepts against cerebral ischemia focus on cell-based therapies in order to overcome some of the side effects of thrombolytic therapy. However, cell-based therapies are hampered because of restricted understanding regarding optimal cell transplantation routes and due to low survival rates of grafted cells. We therefore transplanted adult green fluorescence protein positive neural precursor cells (NPCs) either intravenously (systemic) or intrastriatally (intracerebrally) 6 hours after stroke in mice. To enhance survival of NPCs, cells were in vitro protein-transduced with TAT-heat shock protein 70 (Hsp70) before transplantation followed by a systematic analysis of brain injury and underlying mechanisms depending on cell delivery routes. Transduction of NPCs with TAT-Hsp70 resulted in increased intracerebral numbers of grafted NPCs after intracerebral but not after systemic transplantation. Whereas systemic delivery of either native or transduced NPCs yielded sustained neuroprotection and induced neurological recovery, only TAT-Hsp70-transduced NPCs prevented secondary neuronal degeneration after intracerebral delivery that was associated with enhanced functional outcome. Furthermore, intracerebral transplantation of TAT-Hsp70-transduced NPCs enhanced postischemic neurogenesis and induced sustained high levels of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and vascular endothelial growth factor in vivo. Neuroprotection after intracerebral cell delivery correlated with the amount of surviving NPCs. On the contrary, systemic delivery of NPCs mediated acute neuroprotection via stabilization of the blood-brain-barrier, concomitant with reduced activation of matrix metalloprotease 9 and decreased formation of reactive oxygen species. Our findings imply two different mechanisms of action of intracerebrally and systemically transplanted NPCs, indicating that systemic NPC delivery might be more feasible for translational stroke concepts, lacking a need of in vitro manipulation of NPCs to induce long-term neuroprotection. STEM CELLS2012;30:12971310"],["dc.identifier.doi","10.1002/stem.1098"],["dc.identifier.gro","3142531"],["dc.identifier.isi","000304087300026"],["dc.identifier.pmid","22593021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8892"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1066-5099"],["dc.title","Transduction of Neural Precursor Cells with TAT-Heat Shock Protein 70 Chaperone: Therapeutic Potential Against Ischemic Stroke after Intrastriatal and Systemic Transplantation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1770"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The American Journal of Pathology"],["dc.bibliographiccitation.lastpage","1781"],["dc.bibliographiccitation.volume","178"],["dc.contributor.author","Rau, C. R."],["dc.contributor.author","Hein, K."],["dc.contributor.author","Sättler, M. B."],["dc.contributor.author","Kretzschmar, B."],["dc.contributor.author","Hillgruber, C."],["dc.contributor.author","Mcrae, B. L."],["dc.contributor.author","Diem, R."],["dc.contributor.author","Bähr, M."],["dc.date.accessioned","2017-09-07T11:44:17Z"],["dc.date.available","2017-09-07T11:44:17Z"],["dc.date.issued","2011"],["dc.description.abstract","In multiple sclerosis, long-term disability is caused by axonal and neuronal damage. Established therapies target primarily the inflammatory component of the disease, but fail to prevent neurodegeneration. Fingolimod (codenamed FTY720) is an oral sphingosine 1-phosphate (S1P) receptor modulator with promising results in phase II trials in multiple sclerosis patients and is under further development as a novel treatment for multiple sclerosis. To evaluate whether FTY720 has neuroprotective properties, we tested this drug in a rat model of myelin oligodendrocyte glycoprotein-induced optic neuritis. FTY720 exerted significant anti-inflammatory effects during optic neuritis and reduced inflammation, demyelination, and axonal damage; however, FTY720 treatment did not prevent apoptosis of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve. Consistent with this lack of effect on RGC survival, FTY720 treatment did not improve visual function, nor did it prevent apoptosis of RGCs in vitro. We observed a persistent activation of apoptotic signaling pathways in RGCs under FTY720 treatment, a possible underlying mechanism for the lack of neuroprotection in the presence of strong anti-inflammatory effects, Furthermore, FTY720 shifted the remaining inflammation in the optic nerve toward neurotoxicity by modest up-regulation of potential neurotoxic cytokines. We conclude that FTY720-induced anti-inflammation and axon protection did not of itself protect neurons from apoptotic cell death. (Am J Pathol 2011, 178:1770-1781; DOI: 10.1016/j.ajpath.2011.01.003)"],["dc.identifier.doi","10.1016/j.ajpath.2011.01.003"],["dc.identifier.gro","3142743"],["dc.identifier.isi","000298306700034"],["dc.identifier.pmid","21406175"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/181"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: European Union [LSHM-CT-2005-018637]; Abbott USA"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0002-9440"],["dc.title","Anti-Inflammatory Effects of FTY720 Do Not Prevent Neuronal Cell Loss in a Rat Model of Optic Neuritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","226"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neuroscience Methods"],["dc.bibliographiccitation.lastpage","232"],["dc.bibliographiccitation.volume","171"],["dc.contributor.author","Nagel, Florian"],["dc.contributor.author","Dohm, Christoph P."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Dietz, Gunnar P.H."],["dc.date.accessioned","2018-03-08T09:21:24Z"],["dc.date.available","2018-03-08T09:21:24Z"],["dc.date.issued","2008"],["dc.description.abstract","Cell-penetrating peptides (CPPs), such as the one derived from the human immunodeficiency virus Tat protein, facilitate the delivery of cargoes across cellular membranes. However, questions about the therapeutic potential of CPP-mediated delivery remain. For instance, the impact of the purification procedure on the functionality of Tat-fusion proteins has not been systematically examined. Here, we isolated fusion proteins of the chaperone heat shock protein 70 (Hsp70) and the Tat CPP under denaturing or native conditions. To investigate the therapeutic potential of different recombinant protein preparations, we examined Tat-Hsp70 transduction efficiency and quantified Tat-Hsp70-mediated folding of a chaperone-dependent yellow fluorescent protein in vitro. Transduction efficiency and chaperone activity of Tat-Hsp70-treated cells was significantly higher compared to cells treated with Hsp70. The application of native isolated Tat-Hsp70 had the strongest effect. This chaperone activity correlates with increased viability of cells treated with the recombinant protein after cell death induction with 6-hydroxydopamine. This suggests that the method of recombinant Tat-fusion protein purification influences its functionality. For Tat-Hsp70, the method of choice seems to be isolation under native conditions, for which we present a purification protocol. Our results may contribute to improve Tat-fusion protein application in basic research and may facilitate its use as therapeutic tool, for instance in Parkinson's disease."],["dc.identifier.doi","10.1016/j.jneumeth.2008.03.008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/12868"],["dc.language.iso","en"],["dc.notes.intern","GRO-Li-Import"],["dc.notes.status","final"],["dc.relation.doi","10.1016/j.jneumeth.2008.03.008"],["dc.relation.issn","0165-0270"],["dc.title","Quantitative evaluation of chaperone activity and neuroprotection by different preparations of a cell-penetrating Hsp70"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Markworth, Ronja"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Burk, Katja"],["dc.date.accessioned","2021-10-01T09:58:18Z"],["dc.date.available","2021-10-01T09:58:18Z"],["dc.date.issued","2021"],["dc.description.abstract","Charcot-Marie-Tooth disease (CMT), also known as motor and sensory neuropathy, describes a clinically and genetically heterogenous group of disorders affecting the peripheral nervous system. CMT typically arises in early adulthood and is manifested by progressive loss of motor and sensory functions; however, the mechanisms leading to the pathogenesis are not fully understood. In this review, we discuss disrupted intracellular transport as a common denominator in the pathogenesis of different CMT subtypes. Intracellular transport via the endosomal system is essential for the delivery of lipids, proteins, and organelles bidirectionally to synapses and the soma. As neurons of the peripheral nervous system are amongst the longest neurons in the human body, they are particularly susceptible to damage of the intracellular transport system, leading to a loss in axonal integrity and neuronal death. Interestingly, defects in intracellular transport, both in neurons and Schwann cells, have been found to provoke disease. This review explains the mechanisms of trafficking and subsequently summarizes and discusses the latest findings on how defects in trafficking lead to CMT. A deeper understanding of intracellular trafficking defects in CMT will expand our understanding of CMT pathogenesis and will provide novel approaches for therapeutic treatments."],["dc.description.abstract","Charcot-Marie-Tooth disease (CMT), also known as motor and sensory neuropathy, describes a clinically and genetically heterogenous group of disorders affecting the peripheral nervous system. CMT typically arises in early adulthood and is manifested by progressive loss of motor and sensory functions; however, the mechanisms leading to the pathogenesis are not fully understood. In this review, we discuss disrupted intracellular transport as a common denominator in the pathogenesis of different CMT subtypes. Intracellular transport via the endosomal system is essential for the delivery of lipids, proteins, and organelles bidirectionally to synapses and the soma. As neurons of the peripheral nervous system are amongst the longest neurons in the human body, they are particularly susceptible to damage of the intracellular transport system, leading to a loss in axonal integrity and neuronal death. Interestingly, defects in intracellular transport, both in neurons and Schwann cells, have been found to provoke disease. This review explains the mechanisms of trafficking and subsequently summarizes and discusses the latest findings on how defects in trafficking lead to CMT. A deeper understanding of intracellular trafficking defects in CMT will expand our understanding of CMT pathogenesis and will provide novel approaches for therapeutic treatments."],["dc.identifier.doi","10.3389/fnmol.2021.695294"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90036"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation.eissn","1662-5099"],["dc.title","Held Up in Traffic—Defects in the Trafficking Machinery in Charcot-Marie-Tooth Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","103"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Brain Research Bulletin"],["dc.bibliographiccitation.lastpage","114"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Dietz, Gunnar P. H."],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2017-09-07T11:53:40Z"],["dc.date.available","2017-09-07T11:53:40Z"],["dc.date.issued","2005"],["dc.description.abstract","Over the last 15 years, many publications described the use of peptide sequences that have been dubbed cell penetrating peptides (CPP), Trojan Horse peptides, protein transduction domains, or membrane-translocating sequences. These mostly positively charged domains bring attached cargo across biological membranes. One of the reasons for the interest in CPP is their potential as delivery tools to enhance the pharmacodynamics of drugs otherwise poorly bioavailable. In particular, the neuroscientist aiming to deliver a protein or other compound into the brain for analytical or therapeutic reasons is faced with the challenge that few drugs cross the blood-brain barrier. CPP are valuable tools to overcome the plasma membrane or the blood-brain barrier in basic research, and in relevant models of neural disease, and will hopefully help to increase the precious few treatments or even cures for people with diseases of the brain and nervous system. Here, we review applications in neuroscience and recent insights into the mechanism of CPP-mediated trafficking. (c) 2005 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.brainresbull.2005.08.015"],["dc.identifier.gro","3143771"],["dc.identifier.isi","000234152600013"],["dc.identifier.pmid","16325010"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1321"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0361-9230"],["dc.title","Peptide-enhanced cellular internalization of proteins in neuroscience"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","247"],["dc.bibliographiccitation.issue","3-4"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","264"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Psol, Maryna"],["dc.contributor.author","Darvas, Sofia Guerin"],["dc.contributor.author","Leite, Kristian"],["dc.contributor.author","Mahajani, Sameehan U"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2021-07-05T14:57:32Z"],["dc.date.available","2021-07-05T14:57:32Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Beta (ß)-synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related alpha (α)-synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in central nervous system (CNS) neurons in vitro and in vivo, albeit at a slower pace as compared with α-Syn. Here, we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of dementia with Lewy bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but it has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but it does not aggravate neurodegeneration. ß-Syn wild type (WT), V70M and P123H formed proteinase K-resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared with α-Syn. Under cell-free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared with WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, which are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn and is thus likely to be directly involved into the etiology of DLB. Overall, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn."],["dc.description.abstract","Abstract Beta (ß)-synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related alpha (α)-synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in central nervous system (CNS) neurons in vitro and in vivo, albeit at a slower pace as compared with α-Syn. Here, we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of dementia with Lewy bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but it has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but it does not aggravate neurodegeneration. ß-Syn wild type (WT), V70M and P123H formed proteinase K-resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared with α-Syn. Under cell-free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared with WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, which are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn and is thus likely to be directly involved into the etiology of DLB. Overall, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn."],["dc.identifier.doi","10.1093/hmg/ddab036"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87669"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-441"],["dc.relation.eissn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","Dementia with Lewy bodies—associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","89"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Virology"],["dc.bibliographiccitation.lastpage","95"],["dc.bibliographiccitation.volume","311"],["dc.contributor.author","Kügler, S"],["dc.contributor.author","Schöll, U"],["dc.contributor.author","Zolotukhin, S"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2021-06-01T10:50:07Z"],["dc.date.available","2021-06-01T10:50:07Z"],["dc.date.issued","2003"],["dc.description.abstract","Adeno-associated- (AAV) based vectors are promising tools for gene therapy applications in several organs, including the brain, but are limited by their small genome size. Two short promoters, the human synapsin 1 gene promoter (hSYN) and the murine cytomegalovirus immediate early promoter (mCMV), were evaluated in bicistronic AAV-2 vectors for their expression profiles in cultured primary brain cells and in the rat brain. Whereas transgene expression from the hSYN promoter was exclusively neuronal, the murine CMV promoter targeted expression mainly to astrocytes in vitro and showed weak transgene expression in vivo in retinal and cortical neurons, but strong expression in thalamic neurons. We propose that neuron specific transgene expression in combination with enhanced transgene capacity will further substantially improve AAV based vector technology. (C) 2003 Elsevier Science (USA). All rights reserved."],["dc.identifier.doi","10.1016/S0042-6822(03)00162-4"],["dc.identifier.gro","3144097"],["dc.identifier.isi","000184042900010"],["dc.identifier.pmid","12832206"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86537"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0042-6822"],["dc.title","Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","275"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","276"],["dc.bibliographiccitation.volume","237"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Sommer, Norbert"],["dc.contributor.author","PETERSEN, D."],["dc.contributor.author","WIETHOLTER, H"],["dc.contributor.author","Dichgans, J."],["dc.date.accessioned","2017-09-07T11:51:57Z"],["dc.date.available","2017-09-07T11:51:57Z"],["dc.date.issued","1990"],["dc.identifier.doi","10.1007/BF00314635"],["dc.identifier.gro","3144827"],["dc.identifier.isi","A1990DN81400014"],["dc.identifier.pmid","2391553"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2494"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.issn","0340-5354"],["dc.title","CENTRAL PONTINE MYELINOLYSIS ASSOCIATED WITH LOW POTASSIUM LEVELS IN ALCOHOLISM"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","479"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biochemical and Biophysical Research Communications"],["dc.bibliographiccitation.lastpage","483"],["dc.bibliographiccitation.volume","265"],["dc.contributor.author","Roth, W"],["dc.contributor.author","Isenmann, Stefan"],["dc.contributor.author","Naumann, U."],["dc.contributor.author","Kugler, S."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Dichgans, J."],["dc.contributor.author","Ashkenazi, A."],["dc.contributor.author","Weller, M"],["dc.date.accessioned","2017-09-07T11:47:27Z"],["dc.date.available","2017-09-07T11:47:27Z"],["dc.date.issued","1999"],["dc.description.abstract","Glioblastoma multiforme is a lethal neoplasm refractory to radiochemotherapy, Although glioma cells undergo apoptosis when exposed to the death ligand, CD95 (Fas/APO-1) ligand, the therapeutic use of CD95L is considered impossible because of lethal side effects. Here, we report that the locoregional application of Apoa ligand (Apo2L) exerts strong antitumor activity on preestablished intracranially growing human U87MG glioma xenografts in athymic mice. Two repetitive intratumoral injections of 2 mu g Apo2L resulted in long-term survival of mice (>100 days), whereas the median survival of mock-treated mice was 36 days. The assessment of tumor volumes at 21 and 35 days after inoculation showed complete eradication of glioma xenografts in Apo2L-treated mice. Histology and TUNEL assay confirmed the induction of apoptosis by Apo2L in glioma cells in vivo. Importantly, the intracerebral injection of Apo2L does not result in acute or delayed neurotoxicity. We propose that a phase 1 trial of intralesional Apo2L therapy for human glioblastoma multiforme is warranted. (C) 1999 Academic Press."],["dc.identifier.doi","10.1006/bbrc.1999.1693"],["dc.identifier.gro","3144435"],["dc.identifier.isi","000083899100038"],["dc.identifier.pmid","10558893"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2059"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Inc"],["dc.relation.issn","0006-291X"],["dc.title","Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]