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Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
M. Sramek, J. Neradil, P. Macigova, P. Mudry, K. Polaskova, O. Slaby, H. Noskova, J. Sterba, R. Veselska,
Language English Country Switzerland
Document type Journal Article
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NV16-34083A
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NV16-34083A
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Full text - Article
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Free Medical Journals
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PubMed Central
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PubMed
30200486
DOI
10.3390/ijms19092599
Knihovny.cz E-resources
- MeSH
- Butadienes administration & dosage therapeutic use MeSH
- Child MeSH
- Erlotinib Hydrochloride administration & dosage therapeutic use MeSH
- Phosphorylation drug effects MeSH
- Protein Kinase Inhibitors administration & dosage therapeutic use MeSH
- Infant MeSH
- Humans MeSH
- Mutation * MeSH
- Myofibromatosis congenital drug therapy genetics MeSH
- Cell Line, Tumor MeSH
- Nitriles administration & dosage therapeutic use MeSH
- Cell Proliferation drug effects MeSH
- Pyrazoles administration & dosage therapeutic use MeSH
- Pyridazines administration & dosage therapeutic use MeSH
- Receptor, Platelet-Derived Growth Factor beta * genetics metabolism MeSH
- Sunitinib administration & dosage therapeutic use MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Infantile myofibromatosis represents one of the most common proliferative fibrous tumors of infancy and childhood. More effective treatment is needed for drug-resistant patients, and targeted therapy using specific protein kinase inhibitors could be a promising strategy. To date, several studies have confirmed a connection between the p.R561C mutation in gene encoding platelet-derived growth factor receptor beta (PDGFR-beta) and the development of infantile myofibromatosis. This study aimed to analyze the phosphorylation of important kinases in the NSTS-47 cell line derived from a tumor of a boy with infantile myofibromatosis who harbored the p.R561C mutation in PDGFR-beta. The second aim of this study was to investigate the effects of selected protein kinase inhibitors on cell signaling and the proliferative activity of NSTS-47 cells. We confirmed that this tumor cell line showed very high phosphorylation levels of PDGFR-beta, extracellular signal-regulated kinases (ERK) 1/2 and several other protein kinases. We also observed that PDGFR-beta phosphorylation in tumor cells is reduced by the receptor tyrosine kinase inhibitor sunitinib. In contrast, MAPK/ERK kinases (MEK) 1/2 and ERK1/2 kinases remained constitutively phosphorylated after treatment with sunitinib and other relevant protein kinase inhibitors. Our study showed that sunitinib is a very promising agent that affects the proliferation of tumor cells with a p.R561C mutation in PDGFR-beta.
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- $a Sramek, Martin $u Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic. martin.sramek@mail.muni.cz. Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. martin.sramek@mail.muni.cz. International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. martin.sramek@mail.muni.cz.
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- $a Infantile myofibromatosis represents one of the most common proliferative fibrous tumors of infancy and childhood. More effective treatment is needed for drug-resistant patients, and targeted therapy using specific protein kinase inhibitors could be a promising strategy. To date, several studies have confirmed a connection between the p.R561C mutation in gene encoding platelet-derived growth factor receptor beta (PDGFR-beta) and the development of infantile myofibromatosis. This study aimed to analyze the phosphorylation of important kinases in the NSTS-47 cell line derived from a tumor of a boy with infantile myofibromatosis who harbored the p.R561C mutation in PDGFR-beta. The second aim of this study was to investigate the effects of selected protein kinase inhibitors on cell signaling and the proliferative activity of NSTS-47 cells. We confirmed that this tumor cell line showed very high phosphorylation levels of PDGFR-beta, extracellular signal-regulated kinases (ERK) 1/2 and several other protein kinases. We also observed that PDGFR-beta phosphorylation in tumor cells is reduced by the receptor tyrosine kinase inhibitor sunitinib. In contrast, MAPK/ERK kinases (MEK) 1/2 and ERK1/2 kinases remained constitutively phosphorylated after treatment with sunitinib and other relevant protein kinase inhibitors. Our study showed that sunitinib is a very promising agent that affects the proliferation of tumor cells with a p.R561C mutation in PDGFR-beta.
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