%0 Journal Article %1 Bocci.2004 %A Bocci, G. %A Man, S. %A Green, S. K. %A Francia, G. %A Ebos, J. M. %A Manoir, J. M. Du %A Weinerman, A. %A Emmenegger, U. %A Ma, L. %A Thorpe, P. %A Davidoff, A. %A Huber, J. %A Hicklin, D. J. %A Kerbel, R. S. %D 2004 %J Cancer Res. %K & A Adenocarcinoma Administration Angiogenesis Animals Antibodies Antineoplastic Biological Blood Cell Chemotherapy Colorectal Combined Drug Endothelial Factor Growth Human Humans Inhibitors Line Male Markers Messenger Mice Modality Monoclonal Neoplasms Neovascularization Nude Pathologic Platelets Prostatic Protocols RNA Receptor-2 Research Schedule Scid Therapy Tumor Vascular administration biosynthesis blood dosage genetics immunology metabolism protein supply therapy %N 18 %P 6616-6625 %T Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies %U PM:15374976 %V 64 %X A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non-tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a signi

@article{Bocci.2004, abstract = {A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non-tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a signi}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Bocci, G. and Man, S. and Green, S. K. and Francia, G. and Ebos, J. M. and Manoir, J. M. Du and Weinerman, A. and Emmenegger, U. and Ma, L. and Thorpe, P. and Davidoff, A. and Huber, J. and Hicklin, D. J. and Kerbel, R. S.}, biburl = {https://www.bibsonomy.org/bibtex/202092469557a1e573b6d3861630a2291/kanefendt}, interhash = {fc4c935407df27a00182a6f4e2a52955}, intrahash = {02092469557a1e573b6d3861630a2291}, journal = {Cancer Res.}, keywords = {& A Adenocarcinoma Administration Angiogenesis Animals Antibodies Antineoplastic Biological Blood Cell Chemotherapy Colorectal Combined Drug Endothelial Factor Growth Human Humans Inhibitors Line Male Markers Messenger Mice Modality Monoclonal Neoplasms Neovascularization Nude Pathologic Platelets Prostatic Protocols RNA Receptor-2 Research Schedule Scid Therapy Tumor Vascular administration biosynthesis blood dosage genetics immunology metabolism protein supply therapy}, number = 18, pages = {6616-6625}, timestamp = {2010-02-05T11:28:43.000+0100}, title = {Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies}, url = {PM:15374976}, volume = 64, year = 2004 }