EU Framework 6 Project: Predictive Toxicology (PredTox)—overview and outcome
作者： Laura Suter , Susanne Schroeder , Kirstin Meyer , Jean-Charles Gautier , Alexander Amberg
DOI: 10.1016/J.TAAP.2010.10.008
关键词: Outcome (game theory) 、 Predictive toxicology 、 Identification (biology) 、 Bioinformatics 、 Omics 、 Metabolomics 、 Cholestasis 、 Toxicogenomics 、 Proteomics 、 Biology 、 Toxicology 、 Pharmacology
摘要: Abstract In this publication, we report the outcome of integrated EU Framework 6 Project: Predictive Toxicology (PredTox), including methodological aspects and overall conclusions. Specific details data analysis interpretation are reported in separate articles issue. The project, partly funded by EU, was carried out a consortium 15 pharmaceutical companies, 2 SMEs, 3 universities. effects 16 test compounds were characterized using conventional toxicological parameters “omics” technologies. three major observed toxicities, liver hypertrophy, bile duct necrosis and/or cholestasis, kidney proximal tubular damage analyzed detail. combined approach toxicology proved useful tool for mechanistic investigations identification putative biomarkers. our hands combination with histopathological assessment, target organ transcriptomics most prolific generation hypotheses. Proteomics approaches relatively time-consuming required careful standardization. NMR-based metabolomics detected metabolite changes accompanying findings, providing limited additional information. Conversely, targeted profiling LC/GC-MS very investigation necrosis/cholestasis. general, both proteomics supportive other findings. Thus, program indicates that technologies can help toxicologists to make better informed decisions during exploratory studies. support hypothesis on mode action discovery biomarkers tangible outcomes analysis. Qualification remains challenging, particular terms identification, anchoring, appropriate specificity, sensitivity.
elsevier.com
sci-hub.se 参考文章(21)
M. Adler, D. Hoffmann, H. Ellinger-Ziegelbauer, P. Hewitt, K. Matheis, L. Mulrane, W.M. Gallagher, J.J. Callanan, L. Suter, M.M. Fountoulakis, W. Dekant, A. Mally, Assessment of candidate biomarkers of drug-induced hepatobiliary injury in preclinical toxicity studies Toxicology Letters. ,vol. 196, pp. 1- 11 ,(2010) , 10.1016/J.TOXLET.2010.03.018
Qiang Shi, Huixiao Hong, John Senior, Weida Tong, Biomarkers for drug-induced liver injury. Expert Review of Gastroenterology & Hepatology. ,vol. 4, pp. 225- 234 ,(2010) , 10.1586/EGH.10.8
Leming Shi, Laura H Reid, Wendell D Jones, Richard Shippy, Janet A Warrington, Shawn C Baker, Patrick J Collins, Francoise De Longueville, Ernest S Kawasaki, Kathleen Y Lee, Yuling Luo, Yongming Andrew Sun, James C Willey, Robert A Setterquist, Gavin M Fischer, Weida Tong, Yvonne P Dragan, David J Dix, Felix W Frueh, Federico M Goodsaid, Damir Herman, Roderick V Jensen, Charles D Johnson, Edward K Lobenhofer, Raj K Puri, Uwe Schrf, Jean Thierry-Mieg, Charles Wang, Mike Wilson, Paul K Wolber, Lu Zhang, Shashi Amur, Wenjun Bao, Catalin C Barbacioru, Anne Bergstrom Lucas, Vincent Bertholet, Cecilie Boysen, Bud Bromley, Donna Brown, Alan Brunner, Roger Canales, Xiaoxi Megan Cao, Thomas A Cebula, James J Chen, Jing Cheng, Tzu-Ming Chu, Eugene Chudin, John Corson, J Christopher Corton, Lisa J Croner, Christopher Davies, Timothy S Davison, Glenda Delenstarr, Xutao Deng, David Dorris, Aron C Eklund, Xiao-Hui Fan, Hong Fang, Stephanie Fulmer-Smentek, James C Fuscoe, Kathryn Gallagher, Weigong Ge, Lei Guo, Xu Guo, Janet Hager, Paul K Haje, Jing Han, Tao Han, Heather C Harbottle, Stephen C Harris, Eli Hatchwell, Craig A Hauser, Susan Hester, Huixiao Hong, Patrick Hurban, Scott A Jackson, Hanlee Ji, Charles R Knight, Winston P Kuo, J Eugene LeClerc, Shawn Levy, Quan-Zhen Li, Chunmei Liu, Ying Liu, Michael J Lombardi, Yunqing Ma, Scott R Magnuson, Botoul Maqsodi, Tim McDaniel, Nan Mei, Ola Myklebost, Baitang Ning, Natalia Novoradovskaya, Michael S Orr, Terry W Osborn, Adam Papallo, Tucker A Patterson, Roger G Perkins, Elizabeth H Peters, Ron Peterson, Kenneth L Philips, P Scott Pine, Lajos Pusztai, Feng Qian, Hongzu Ren, Mitch Rosen, Barry A Rosenzweig, Raymond R Samaha, Mark Schena, Gary P Schroth, Svetlana Shchegrova, Dave D Smith, Frank Staedtler, Zhenqiang Su, Hongmei Sun, Zoltan Szallasi, Zivana Tezak, Danielle Thierry-Mieg, Karol L Thompson, Irina Tikhonova, Yaron Turpaz, Beena Vallanat, Christophe Van, Stephen J Walker, Sue Jane Wang, Yonghong Wang, Russ Wolfinger, Alex Wong, Jie Wu, Chunlin Xiao, Qian Xie, Jun Xu, Wen Yang, S Zhong, Y Zong, W Slikker Jr, None, The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements Nature Biotechnology. ,vol. 24, pp. 1151- 1161 ,(2006) , 10.1038/NBT1239
William M. Gallagher, David Tweats, Jochen Koenig, Omic profiling for drug safety assessment: current trends and public–private partnerships Drug Discovery Today. ,vol. 14, pp. 337- 342 ,(2009) , 10.1016/J.DRUDIS.2009.02.001
Heidrun Ellinger-Ziegelbauer, Melanie Adler, Alexander Amberg, Arnd Brandenburg, John J. Callanan, Susan Connor, Michael Fountoulakis, Hans Gmuender, Albrecht Gruhler, Philip Hewitt, Mark Hodson, Katja A. Matheis, Diane McCarthy, Marian Raschke, Björn Riefke, Christina S. Schmitt, Max Sieber, Alexandra Sposny, Laura Suter, Brian Sweatman, Angela Mally, The enhanced value of combining conventional and “omics” analyses in early assessment of drug-induced hepatobiliary injury Toxicology and Applied Pharmacology. ,vol. 252, pp. 97- 111 ,(2011) , 10.1016/J.TAAP.2010.09.022
Lei Guo, Edward K Lobenhofer, Charles Wang, Richard Shippy, Stephen C Harris, Lu Zhang, Nan Mei, Tao Chen, Damir Herman, Federico M Goodsaid, Patrick Hurban, Kenneth L Phillips, Jun Xu, Xutao Deng, Yongming Andrew Sun, Weida Tong, Yvonne P Dragan, Leming Shi, Rat toxicogenomic study reveals analytical consistency across microarray platforms Nature Biotechnology. ,vol. 24, pp. 1162- 1169 ,(2006) , 10.1038/NBT1238
Katja A. Matheis, Emmanuelle Com, Jean-Charles Gautier, Nelson Guerreiro, Arnd Brandenburg, Hans Gmuender, Alexandra Sposny, Philip Hewitt, Alexander Amberg, Olaf Boernsen, Bjoern Riefke, Dana Hoffmann, Angela Mally, Arno Kalkuhl, Laura Suter, Frank Dieterle, Frank Staedtler, Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers Toxicology and Applied Pharmacology. ,vol. 252, pp. 112- 122 ,(2011) , 10.1016/J.TAAP.2010.11.006
Hector C Keun, Toby J Athersuch, Application of metabonomics in drug development Pharmacogenomics. ,vol. 8, pp. 731- 741 ,(2007) , 10.2217/14622416.8.7.731
Harry Olson, Graham Betton, Jeffrey Stritar, Denise Robinson, The predictivity of the toxicity of pharmaceuticals in humans from animal data--an interim assessment. Toxicology Letters. ,vol. 102, pp. 535- 538 ,(1998) , 10.1016/S0378-4274(98)00261-6
S RUEPP, F BOESS, L SUTER, M DEVERA, G STEINER, T STEELE, T WEISER, S ALBERTINI, Assessment of hepatotoxic liabilities by transcript profiling. Toxicology and Applied Pharmacology. ,vol. 207, pp. 161- 170 ,(2005) , 10.1016/J.TAAP.2005.05.008