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• W2232094228 abstract "4737 Background: Hormone refractory prostate cancer (HRPC) has been a therapeutic challenge due to limited response to treatment. Prominent cell signaling pathways in tumor growth are mediated by tyrosinekinase (TK) receptors. Platelet-derived growth factor receptors (PDGF-R) are expressed in prostate cancer but not in benign prostate hyperplasia or normal prostatic epithelium. Imatinib (STI571, Gleevec®) is a selective inhibitor of the PDGF-R. The aim of this in vitro study was to evaluate cytotoxic effects of Imatinib in combination with commonly used chemotherapeutics for HRPC. Methods: The human prostate cancer cell lines LNCaP (androgen dependend), PC-3 and DU-145 (androgen refractory) were screened for TK receptors by immuncytochemical analysis. C-kit was expressed in none of these cell lines. The expression pattern of PDGF-R were different among these cell lines and will be presented. Variable cell growth was determined by XTT reduction assay. Cell lines were incubated 96 hours with rising concentrations of Imatinib alone and in combination with Etoposide, Doxetacel, and Estramustinphosphate (EMP). The cytotoxic interaction were evaluated by isobolograms as described by Steel & Peckham. Results: Imatinib showed dose-depended growth inhibition with nearly complete cell death in all three cell lines. The IC50-values of Imatinib for LNCaP, PC-3 and DU-145 were 12,48 μM, 11,68 μM and 16,24 μM respectively. Simultaneous exposure of Imatinib and Etoposide suggested additive to synergistic effects in DU-145. The combination of Imatinib and EMP showed additive effects in all three cell lines. Combination of Imatinib and Doxetacel resulted in additive to antagonistic effects in DU-145 and LNCaP, whereas in PC-3 antagonistic effects were observed. Conclusions: The simultaneous administration of Imatinib and Etposide resulted in additive to synergistic effects in DU-145. The combination with EMP produced additive effects in hormone refractory as well as hormone sensitive cell lines. Based on these encouraging in vitro data clinical trials of Imatinib with these promising combinations are planned in HRPC. No significant financial relationships to disclose." @default.
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• W2232094228 date "2004-07-15" @default.
• W2232094228 modified "2023-09-25" @default.
• W2232094228 title "Combined application of imatinib and standard chemotherapeutics results in additive cytotoxic effects in human prostate cancer cell lines" @default.
• W2232094228 doi "https://doi.org/10.1200/jco.2004.22.90140.4737" @default.
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