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Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival
S. Al Shboul, OE. Curran, JA. Alfaro, F. Lickiss, E. Nita, J. Kowalski, F. Naji, R. Nenutil, KL. Ball, R. Krejcir, B. Vojtesek, TR. Hupp, PM. Brennan
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
BB/C511599/1
Biotechnology and Biological Sciences Research Council - United Kingdom
BB/J00751X/1
Biotechnology and Biological Sciences Research Council - United Kingdom
NLK
Directory of Open Access Journals
od 2018
Freely Accessible Science Journals
od 2018
PubMed Central
od 2018
ROAD: Directory of Open Access Scholarly Resources
od 2018
PubMed
34645618
DOI
10.26508/lsa.202101054
Knihovny.cz E-zdroje
- MeSH
- glioblastom enzymologie mortalita patologie MeSH
- kokultivační techniky metody MeSH
- lidé MeSH
- míra přežití MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky enzymologie MeSH
- nádory mozku enzymologie mortalita patologie MeSH
- proteinkinasa BTK metabolismus MeSH
- proteom metabolismus MeSH
- proteomika metody MeSH
- signální transdukce * MeSH
- transkripční faktory SOXB1 metabolismus MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Better understanding of GBM signalling networks in-vivo would help develop more physiologically relevant ex vivo models to support therapeutic discovery. A "functional proteomics" screen was undertaken to measure the specific activity of a set of protein kinases in a two-step cell-free biochemical assay to define dominant kinase activities to identify potentially novel drug targets that may have been overlooked in studies interrogating GBM-derived cell lines. A dominant kinase activity derived from the tumour tissue, but not patient-derived GBM stem-like cell lines, was Bruton tyrosine kinase (BTK). We demonstrate that BTK is expressed in more than one cell type within GBM tissue; SOX2-positive cells, CD163-positive cells, CD68-positive cells, and an unidentified cell population which is SOX2-negative CD163-negative and/or CD68-negative. The data provide a strategy to better mimic GBM tissue ex vivo by reconstituting more physiologically heterogeneous cell co-culture models including BTK-positive/negative cancer and immune cells. These data also have implications for the design and/or interpretation of emerging clinical trials using BTK inhibitors because BTK expression within GBM tissue was linked to longer patient survival.
Cardiff University Hospital Cellular Pathology Cardiff UK
Department of Basic Medical Sciences Faculty of Medicine The Hashemite University Zarqa Jordan
Department of Neuropathology Western General Hospital Edinburgh UK
Institute of Genetics and Cancer University of Edinburgh Edinburgh UK
International Centre for Cancer Vaccine Science University of Gdansk Gdansk Poland
Pamgene International BV 's Hertogenbosch Netherlands
Research Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute Brno Czech Republic
Translational Neurosurgery Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK
Citace poskytuje Crossref.org
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