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3篇 您的检索式:作者名="Katja Rateitschak"
    题名 作者 年代 出处 被引量
1Systems biology of JAK-STAT signalling in human malignancies显示文摘Julio Vera Katja Rateitschak Falko Lange Christina Kossow Olaf Wolkenhauer Robert Jaster 2011Progress in Biophysics and Molecular Biology2011,,2:1
2Mathematical modelling of interferon-γ signalling in pancreatic stellate cells reflects and predicts the dynamics of STAT1 pathway activity显示文摘Katja Rateitschak Anna Karger Brit Fitzner Falko Lange Olaf Wolkenhauer Robert Jaster 2009Cellular Signalling2009,,1:1
3Insights into erlotinib action in pancreatic cancer cells using a combined experimental and mathematical approach显示文摘AIM:To gain insights into the molecular action of erlotinib in pancreatic cancer (PC) cells. METHODS:Two PC cell lines, BxPC-3 and Capan-1, were treated with various concentrations of erlotinib, the specific mitogen-activated protein kinase kinase (MEK) inhibitor U0126, and protein kinase B (AKT) inhibitor XIV. DNA synthesis was measured by 5-bromo-2'-deoxyuridine (BrdU) assays. Expression and phosphorylation of the epidermal growth factor receptor (EGFR) and downstream signaling molecules were quantified by Western blot analysis. The data were processed to calibrate a mathematical model, based on ordinary differential equations, describing the EGFRmediated signal transduction. RESULTS:Erlotinib significantly inhibited BrdU incorporation in BxPC-3 cells at a concentration of 1 mol/L, whereas Capan-1 cells were much more resistant. In both cell lines, MEK inhibitor U0126 and erlotinib attenuated DNA synthesis in a cumulative manner, whereas the AKT pathway-specific inhibitor did not enhance the effects of erlotinib. While basal phosphorylation of EGFR and extracellular signal-regulated kinase (ERK) did not differ much between the two cell lines, BxPC-3 cells displayed a more than five-times higher basal phospho-AKT level than Capan-1 cells. Epidermal growth factor (EGF) at 10 ng/mL induced the phosphorylation of EGFR, AKT and ERK in both cell lines with similar kinetics. In BxPC-3 cells, higher levels of phospho-AKT and phospho-ERK (normalized to the total protein levels) were observed. Independent of the cell line, erlotinib efficiently inhibited phosphorylation of EGFR, AKT and ERK. The mathematical model successfully simulated the experimental findings and provided predictions regarding phosphoprotein levels that could be verified experimentally. CONCLUSION:Our data suggest basal AKT phosphorylation and the degree of EGF-induced activation of AKT and ERK as molecular determinants of erlotinib efficiency in PC cells.Falko Lange Katja Rateitschak Christina Kossow Olaf Wolkenhauer Robert Jaster 2012World Journal of Gastroenterology2012,18,43:1
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