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Kinome Profiling of Chondrosarcoma Reveals Src-Pathway Activity and Dasatinib as Option for Treatment

Kinome Profiling of Chondrosarcoma Reveals Src-Pathway Activity and Dasatinib as Option for Treatment,10.1158/0008-5472.CAN-08-4801,Cancer Research,Y.

Kinome Profiling of Chondrosarcoma Reveals Src-Pathway Activity and Dasatinib as Option for Treatment   (Citations: 9)
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Journal: Cancer Research - CANCER RES , vol. 69, no. 15, pp. 6216-6222, 2009
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    • ...After adequate resection, 10-year survival for patients with grade I chondrosarcoma is excellent, whereas only 64% for grade II and 29% for grade III tumors [8]...

    Philipp Lechleret al. The antiapoptotic gene survivin is highly expressed in human chondrosa...

    • ...However, recently various promising targets were discovered and the exploration of suitable therapies continues [3,4]...

    Danielle Meijeret al. Expression of aromatase and estrogen receptor alpha in chondrosarcoma,...

    • ... Kinase activity profiling shows that the most active kinase in chondrosarcoma is AK...

    Judith V. M. G. Bovéeet al. Cartilage tumours and bone development: molecular pathology and possib...

    • ...Moreover, kinases are promising targets for anti-cancer therapy as they do not require new protein synthesis, therefore act rapidly and are also promising in slow-cycling tumors [16,17]...
    • ...myxoid liposarcoma) was additionally verified by comparison with the same analysis in four colorectal carcinoma cell lines and thirteen chondrosarcoma cell lines and cultures using Limma, which revealed a different list of substrates and kinases [16]...
    • ...pathways known to be involved in GIST [16]...
    • ...Moreover, we previously demonstrated the reliability of our analysis which is based on averaging results of a number of samples to get an impression of the most activated kinases in a series of tumors [16]...
    • ...The Src pathway can be inhibited by the small molecule tyrosine kinase inhibitor dasatinib limiting cell growth in various cancers in vitro, thereby having promising therapeutic potential [16,50,51]...
    • ...Kinase substrate peptide arrays (Pepchip Kinomics, Pepscan Presto, Lelystad, the Netherlands) containing 1024 different kinase substrates spotted in triplicate together with 16 negative, and 16 positive controls were used and successfully used in prior studies [16,59]...
    • ...Analysis was performed as described earlier, including the two serum-starved samples [16]...
    • ...Quality of the triplicates and distribution of the data was assessed and quartile normalization (Affyio) was performed as previously described [16]...
    • ...Data of the myxoid liposarcoma cell lines and cultures were averaged to find the common denominators that are active in all cultures [16]...
    • ...Specificity of activated kinases and activated pathways in myxoid liposarcoma was verified by comparison the same analysis of four colorectal carcinoma cell lines and thirteen chondrosarcoma cell lines and cultures using Limma [16]...
    • ...GIST882 and Jurkat cell lines were used as positive controls for dasatinib and TBB experiments, respectively [16]y...

    Stefan M Willemset al. Kinome profiling of myxoid liposarcoma reveals NF-kappaB-pathway kinas...

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