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Erbe ausgeschlagen?
(2011)
Vom 28. bis 30. Januar [2011] lud Günter Grass auch in diesem Jahr wieder ausgewählte Autoren zum Lübecker Literaturtreffen ein, um über dies und das zu debattieren. Mit einer Neuauflage der berühmt berüchtigten Gruppe 47 hat das Treffen nichts zu tun. Aber wofür stehen die Autoren? (...) Neun Autoren sind angereist, so viele wie noch nie; Altbekannte und weniger Bekannte, manche zum ersten, einige bereits zum sechsten Mal: Sherko Fatah, Olga Flor, Eleonora Hummel, Eva Menasse, Norbert Niemann, Knud Romer, Fridolin Schley, Jens Sparschuh und Tilman Spengler.
Pop theoretisch
(2011)
Konzepte, Philosophie und Ästhetik des Pop-Phänomens zwischen Postmoderne, Tradition, Medien und Massenkultur erörtert Christoph Rauen in seiner umfassenden, akribisch recherchierten Studie Pop und Ironie. Popdiskurs und Popliteratur um 1980 und 2000 In den späten 1990er bis in die 2000er Jahre schwemmte eine Flut junger Autoren der sogenannten Popliteratur die Sparten der deutschen Literaturkritik und Feuilletons. Bis auf einige schnell verfasste ambitionierte Studien tat sich die Literaturwissenschaft zunächst schwer, dem Phänomen einen akademisch begründeten Platz in der Forschung einzuräumen. Inzwischen belegt eine Vielzahl fundierter und interessanter Arbeiten, dass es sich auch bei der Popliteratur der letzten 15 Jahre um eine theoretisch ernst zu nehmende und zu begründende Erscheinung der jüngsten Gegenwartsliteratur handelt. Christoph Rauen zeigt in seiner kulturgeschichtlichen und literatursoziologischen Studie Pop und Ironie. Popdiskurs und Popliteratur um 1980 und 2000, auf welche komplexen theoretischen Überlegungen die jüngste Popliteratur gelesen werden kann, indem er das rezeptive Verhältnis der „Neo-Popliteratur“ (Rauen) der späten 1990er und 2000er Jahre zu den Pop- und Ironiekonzepten der 1980er Jahre analysiert.
Ceritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumor
(2019)
The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.
Background: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood.
Methodology/Principal Findings: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor.
Conclusions/Significance: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.
Background: Blunt chest (thoracic) trauma (TxT) and haemorrhagic shock with subsequent resuscitation (H/R) induce strong systemic and local inflammatory response, which is closely associated with apoptotic cell loss and subsequently impaired organ function. The underlying mechanisms are not completely understood, therefore, the treatment of patients suffering from TxT+H/R is challenging. In our recent studies, we have demonstrated local anti-inflammatory effects of ethyl pyruvate (EtP) in lung and liver after TxT+H/R. Here, the therapeutic potential of a reperfusion regime with EtP on the early post-traumatic systemic inflammatory response and apoptotic changes after TxT followed by H/R were investigated.
Methods: Female Lewis rats underwent TxT followed by haemorrhagic shock (60 min). Resuscitation was performed with own blood transfusion and either lactated Ringers solution (LR) or LR supplemented with EtP (50 mg/kg). Sham group underwent the surgical procedures. After 2 h blood as well as lung and liver tissues were obtained for analyses. Systemic activation of neutrophils (expression of CD11b and CD62L), leukocyte phagocytosis, apoptosis (caspase-3/7 activation), pyroptosis (caspase-1 activation) and NF-κB p65 activity were assessed. p < 0.05 was considered significant.
Results: TxT+H/R-induced systemic activation of neutrophils (increased CD11b and reduced CD62L expression) was significantly reduced by EtP. Trauma-induced delayed neutrophil apoptosis was further reduced by EtP reperfusion but remained unaltered in monocytes. Reperfusion with EtP significantly increased the phagocytizing capacity of granulocytes. Trauma-induced inflammasome activation, which was observed in monocytes and not in neutrophils, was significantly reduced by EtP in both cell entities. NF-κB p65 activation, which was increased in neutrophils and monocytes was significantly decreased in monocytes.
Conclusion: TxT+H/R-induced systemic activation of both neutrophils and monocytes concomitant with increased systemic inflammation was reduced by a reperfusion with EtP and was associated with a down-regulation of NF-κB p65 activation.