Recently, the conserved intracellular digestion mechanism 'autophagy' has been considered to be involved in early tumorigenesis and its blockade proposed as an alternative treatment approach. ...However, there is an ongoing debate about whether blocking autophagy has positive or negative effects in tumor cells. Since there is only poor data about the clinico-pathological relevance of autophagy in gliomas in vivo, we first established a cell culture based platform for the in vivo detection of the autophago-lysosomal components. We then investigated key autophagosomal (LC3B, p62, BAG3, Beclin1) and lysosomal (CTSB, LAMP2) molecules in 350 gliomas using immunohistochemistry, immunofluorescence, immunoblotting and qPCR. Autophagy was induced pharmacologically or by altering oxygen and nutrient levels. Our results show that autophagy is enhanced in astrocytomas as compared to normal CNS tissue, but largely independent from the WHO grade and patient survival. A strong upregulation of LC3B, p62, LAMP2 and CTSB was detected in perinecrotic areas in glioblastomas suggesting micro-environmental changes as a driver of autophagy induction in gliomas. Furthermore, glucose restriction induced autophagy in a concentration-dependent manner while hypoxia or amino acid starvation had considerably lesser effects. Apoptosis and autophagy were separately induced in glioma cells both in vitro and in vivo. In conclusion, our findings indicate that autophagy in gliomas is rather driven by micro-environmental changes than by primary glioma-intrinsic features thus challenging the concept of exploitation of the autophago-lysosomal network (ALN) as a treatment approach in gliomas.
Different layer architectures produced by only MOD, only MOCVD and combinations of MOD buffers and MOCVD YBCO are presented. RTR MOCVD-YBCO layers obtained on MOD-CeO 2 /MOD-LZO/Ni5 at%W tapes ...demonstrate critical current densities up to 2 MA/cm 2 at 77 K. On single LZO (50-100 nm) buffered Ni5 at%W tapes from Nexans Superconductors and on RTR MOCVD buffer layers critical current densities between 0.8 and 1.3 MA/cm are obtained. RTR MOD-LZO layers often show delamination during YBCO deposition. Preannealing treatment before YBCO deposition allows to avoid this. Tapes up to 10 m are produced by combination of MOD-LZO and RTR MOCVD-YBCO.
Sympathoadrenergic progenitor cells (SAPs) of the peripheral nervous system (PNS) are important for normal development of the sympathetic PNS and for the genesis of neuroblastoma, the most common and ...often lethal extracranial solid tumor in childhood. However, it remains difficult to isolate sufficient numbers of SAPs for investigations. We therefore set out to improve generation of SAPs by using two complementary approaches, differentiation from murine embryonic stem cells (ESCs) and isolation from postnatal murine adrenal glands. We provide evidence that selecting for GD2 expression enriches for ESC-derived SAP-like cells and that proliferating SAP-like cells can be isolated from postnatal adrenal glands of mice. These advances may facilitate investigations about the development and malignant transformation of the sympathetic PNS.
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