WFRF:(Karlsson Erik A.)
Sökning: WFRF:(Karlsson Erik A.) > (2010-2014) > Intracellular conce...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04328naa a2200457 4500 | |
| 001 | oai:DiVA.org:uu-220136 | |
| 003 | SwePub | |
| 008 | 140311s2014 | |||||||||||000 ||eng| | |
| 009 | oai:prod.swepub.kib.ki.se:128502668 | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2201362 URI |
| 024 | 7 | a https://doi.org/10.1097/CAD.00000000000000692 DOI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1285026682 URI |
| 040 | a (SwePub)uud (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Berglund, Eriku Karolinska Institutet4 aut |
| 245 | 1 0 | a Intracellular concentration of the tyrosine kinase inhibitor imatinib in gastrointestinal stromal tumor cells. |
| 264 | 1 | c 2014 |
| 338 | a print2 rdacarrier | |
| 520 | a Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract. In most GISTs, the underlying mechanism is a gain-of-function mutation in the KIT or the PDGFRA gene. Imatinib is a tyrosine kinase inhibitor that specifically blocks the intracellular ATP-binding sites of these receptors. A correlation exists between plasma levels of imatinib and progression-free survival, but it is not known whether the plasma concentration correlates with the intracellular drug concentration. We determined intracellular imatinib levels in two GIST cell lines: the imatinib-sensitive GIST882 and the imatinib-resistant GIST48. After exposing the GIST cells to imatinib, the intracellular concentrations were evaluated using LC-MS (TOF). The concentration of imatinib in clinical samples from three patients was also determined to assess the validity and reliability of the method in the clinical setting. Determination of imatinib uptake fits within detection levels and values are highly reproducible. The GIST48 cells showed significantly lower imatinib uptake compared with GIST882 in therapeutic doses, indicating a possible difference in uptake mechanisms. Furthermore, imatinib accumulated in the tumor tissues and showed intratumoral regional differences. These data show, for the first time, a feasible and reproducible technique to measure intracellular imatinib levels in experimental and clinical settings. The difference in the intracellular imatinib concentration between the cell lines and clinical samples indicates that drug transporters may contribute toward resistance mechanisms in GIST cells. This highlights the importance of further clinical studies to quantify drug transporter expression and measure intracellular imatinib levels in GIST patients. | |
| 650 | 7 | a NATURVETENSKAPx Kemix Analytisk kemi0 (SwePub)104012 hsv//swe |
| 650 | 7 | a NATURAL SCIENCESx Chemical Sciencesx Analytical Chemistry0 (SwePub)104012 hsv//eng |
| 700 | 1 | a Ubhayasekera, Sarojini J.K.A.u Karolinska Institutet,Uppsala universitet,Analytisk kemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)kumub884 |
| 700 | 1 | a Karlsson, Fredriku Karolinska Institutet4 aut |
| 700 | 1 | a Akcakaya, Pinaru Karolinska Institutet4 aut |
| 700 | 1 | a Aluthgedara, Warunikau Uppsala universitet,Analytisk kemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)waral901 |
| 700 | 1 | a Ahlen, Janu Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet AND Department of Breast and Endocrine Surgery, Karolinska University Hospital4 aut |
| 700 | 1 | a Fröbom, Robinu Karolinska Institutet4 aut |
| 700 | 1 | a Nilsson, Inga-Lenau Karolinska Institutet4 aut |
| 700 | 1 | a Lui, Weng-Onnu Karolinska Institutet4 aut |
| 700 | 1 | a Larsson, Catharinau Karolinska Institutet4 aut |
| 700 | 1 | a Zedenius, Janu Karolinska Institutet4 aut |
| 700 | 1 | a Bergquist, Jonasu Uppsala universitet,Analytisk kemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)jbe25356 |
| 700 | 1 | a Bränström, Robertu Karolinska Institutet4 aut |
| 710 | 2 | a Karolinska Institutetb Analytisk kemi4 org |
| 773 | 0 | t Anti-Cancer Drugsg 25:4, s. 415-22q 25:4<415-22x 0959-4973x 1473-5741 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-220136 |
| 856 | 4 8 | u https://doi.org/10.1097/CAD.0000000000000069 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:128502668 |
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