Regulation der Rezeptor Tyrosin Kinase AXL als Antwort auf Therapie und die Rolle von AXL in Therapie-Resistenz beim Glioblastom
| العنوان: | Regulation der Rezeptor Tyrosin Kinase AXL als Antwort auf Therapie und die Rolle von AXL in Therapie-Resistenz beim Glioblastom |
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| المؤلفون: | Lea Scherschinski, Markus Prem, Irina Kremenetskaia, Ingeborg Tinhofer, Peter Vajkoczy, Anna-Gila Karbe, Julia Sophie Onken |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 982, p 982 (2022) International Journal of Molecular Sciences; Volume 23; Issue 2; Pages: 982 International Journal of Molecular Sciences 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie; 20220529-20220601; Köln; DOCV285 /20220525/ |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cell Survival, QH301-705.5, tyrosine kinase inhibitor (TKI), R428, temozolomide, Catalysis, Article, Inorganic Chemistry, glioblastoma multiforme, Cell Line, Tumor, Proto-Oncogene Proteins, RTK-AXL, Humans, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, post-translational receptor modification, QD1-999, Spectroscopy, Cell Proliferation, radiation, Brain Neoplasms, Organic Chemistry, fungi, Receptor Protein-Tyrosine Kinases, General Medicine, Triazoles, Combined Modality Therapy, Axl Receptor Tyrosine Kinase, Computer Science Applications, nervous system diseases, Up-Regulation, Gene Expression Regulation, Neoplastic, Benzocycloheptenes, Chemistry, ddc: 610, Drug Resistance, Neoplasm, Medicine and health, Tumor Hypoxia, Glioblastoma, Signal Transduction |
| الوصف: | The receptor tyrosine kinase AXL (RTK-AXL) is implicated in therapy resistance and tumor progression in glioblastoma multiforme (GBM). Here, we investigated therapy-induced receptor modifications and how endogenous RTK-AXL expression and RTK-AXL inhibition contribute to therapy resistance in GBM. GBM cell lines U118MG and SF126 were exposed to temozolomide (TMZ) and radiation (RTX). Receptor modifications in response to therapy were investigated on protein and mRNA levels. TMZ-resistant and RTK-AXL overexpressing cell lines were exposed to increasing doses of TMZ and RTX, with and without RTK-AXL tyrosine kinase inhibitor (TKI). Colorimetric microtiter (MTT) assay and colony formation assay (CFA) were used to assess cell viability. Results showed that the RTK-AXL shedding product, C-terminal AXL (CT-AXL), rises in response to repeated TMZ doses and under hypoxia, acts as a surrogate marker for radio-resistance. Endogenous RTX-AXL overexpression leads to therapy resistance, whereas combination therapy of TZM and RTX with TKI R428 significantly increases therapeutic effects. This data proves the role of RTK-AXL in acquired and intrinsic therapy resistance. By demonstrating that therapy resistance may be overcome by combining AXL TKI with standard treatments, we have provided a rationale for future study designs investigating AXL TKIs in GBM. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5a63be703282dbfe0d40a22c324b3234 https://www.mdpi.com/1422-0067/23/2/982 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5a63be703282dbfe0d40a22c324b3234 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16616596 14220067 |
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