%0 Journal Article %1 Luo.2005 %A Luo, F. R. %A Yang, Z. %A Dong, H. %A Camuso, A. %A McGlinchey, K. %A Fager, K. %A Flefleh, C. %A Kan, D. %A Inigo, I. %A Castaneda, S. %A Wong, T. W. %A Kramer, R. A. %A Wild, R. %A Lee, F. Y. %D 2005 %J Clin.Cancer Res. %K Agents Animals Antibodies Antigen Antineoplastic Antitumor Assay Assays Biological Carcinoma Cell Chemistry Colonic Enzyme-Linked Epidermal Factor Factors Female G Growth Human Humans Immunoglobulin Immunohistochemistry Immunosorbent Ki-67 Kinase Line MAP Markers Mice Model Monoclonal Neoplasm Neoplasms Nude Pharmacokinetics Phosphorylation Receptor Research Signaling System Time Transplantation Tumor Tyrosine Xenograft analysis biosynthesis drug metabolism methods pathology pharmacology protein response therapy %N 15 %P 5558-5565 %T Prediction of active drug plasma concentrations achieved in cancer patients by pharmacodynamic biomarkers identified from the geo human colon carcinoma xenograft model %U PM:16061873 %V 11 %X PURPOSE: Epidermal growth factor receptor (EGFR), a protein tyrosine kinase expressed in many types of human cancers, has been strongly associated with tumor progression. Cetuximab is an IgG(1) anti-EGFR chimeric mouse/human monoclonal antibody that has been approved for the treatment of advanced colon cancer. Using human tumor xenografts grown in nude mice, we have determined the in vivo pharmacodynamic response of cetuximab at efficacious doses. Three pharmacodynamic end points were evaluated: tumoral phospho-EGFR, tumoral mitogen-activated protein kinase (MAPK) phosphorylation, and Ki67 expression. EXPERIMENTAL DESIGN: The pharmacodynamic study was conducted in nude mice bearing Geo tumors following a single i.p. administration of 0.25 and 0.04 mg. The tumors were analyzed by immunohistochemistry. The levels of phospho-EGFR were quantitated by an ELISA assay. RESULTS: At 0.25 mg, phospho-EGFR was maximally inhibited by 91% at 24 hours, whereas the level of inhibition decreased to 72

@article{Luo.2005, abstract = {PURPOSE: Epidermal growth factor receptor (EGFR), a protein tyrosine kinase expressed in many types of human cancers, has been strongly associated with tumor progression. Cetuximab is an IgG(1) anti-EGFR chimeric mouse/human monoclonal antibody that has been approved for the treatment of advanced colon cancer. Using human tumor xenografts grown in nude mice, we have determined the in vivo pharmacodynamic response of cetuximab at efficacious doses. Three pharmacodynamic end points were evaluated: tumoral phospho-EGFR, tumoral mitogen-activated protein kinase (MAPK) phosphorylation, and Ki67 expression. EXPERIMENTAL DESIGN: The pharmacodynamic study was conducted in nude mice bearing Geo tumors following a single i.p. administration of 0.25 and 0.04 mg. The tumors were analyzed by immunohistochemistry. The levels of phospho-EGFR were quantitated by an ELISA assay. RESULTS: At 0.25 mg, phospho-EGFR was maximally inhibited by 91% at 24 hours, whereas the level of inhibition decreased to 72}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Luo, F. R. and Yang, Z. and Dong, H. and Camuso, A. and McGlinchey, K. and Fager, K. and Flefleh, C. and Kan, D. and Inigo, I. and Castaneda, S. and Wong, T. W. and Kramer, R. A. and Wild, R. and Lee, F. Y.}, biburl = {https://www.bibsonomy.org/bibtex/2853643c851098d66d2e16a17fb34377a/kanefendt}, interhash = {de741ace7695c184dfb6ab2bc3fe8f9c}, intrahash = {853643c851098d66d2e16a17fb34377a}, journal = {Clin.Cancer Res.}, keywords = {Agents Animals Antibodies Antigen Antineoplastic Antitumor Assay Assays Biological Carcinoma Cell Chemistry Colonic Enzyme-Linked Epidermal Factor Factors Female G Growth Human Humans Immunoglobulin Immunohistochemistry Immunosorbent Ki-67 Kinase Line MAP Markers Mice Model Monoclonal Neoplasm Neoplasms Nude Pharmacokinetics Phosphorylation Receptor Research Signaling System Time Transplantation Tumor Tyrosine Xenograft analysis biosynthesis drug metabolism methods pathology pharmacology protein response therapy}, number = 15, pages = {5558-5565}, timestamp = {2010-02-05T11:28:41.000+0100}, title = {Prediction of active drug plasma concentrations achieved in cancer patients by pharmacodynamic biomarkers identified from the geo human colon carcinoma xenograft model}, url = {PM:16061873}, volume = 11, year = 2005 }