TY  - JOUR
A1  - Kapelyukh, Yury
A1  - Henderson, Colin James
A1  - Scheer, Nico
A1  - Rode, Anja
A1  - Wolf, Charles Roland
T1  - Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice
JF  - Drug Metabolism and Disposition
Y1  - 2019
U6  - http://dx.doi.org/10.1124/dmd.119.087718
IS  - Early view
ER  - 
TY  - JOUR
A1  - Lempiäinen, Harri
A1  - Couttet, Philippe
A1  - Bolognani, Federico
A1  - Müller, Arne
A1  - Dubost, Valérie
A1  - Luisier, Raphaëlle
A1  - Rio-Espinola, Alberto del
A1  - Vitry, Veronique
A1  - Unterberger, Elif B.
A1  - Thomson, John P.
A1  - Treindl, Fridolin
A1  - Metzger, Ute
A1  - Wrzodek, Clemens
A1  - Hahne, Florian
A1  - Zollinger, Tulipan
A1  - Brasa, Sarah
A1  - Kalteis, Magdalena
A1  - Marcellin, Magali
A1  - Giudicelli, Fanny
A1  - Braeuning, Albert
A1  - Morawiec, Laurent
A1  - Zamurovic, Natasa
A1  - Längle, Ulrich
A1  - Scheer, Nico
A1  - Schübeler, Dirk
A1  - Goodman, Jay
A1  - Chibout, Salah-Dine
A1  - Marlowe, Jennifer
A1  - Theil, Dietlinde
A1  - Heard, David J.
A1  - Grenet, Olivier
A1  - Zell, Andreas
A1  - Templin, Markus F.
A1  - Meehan, Richard R.
A1  - Wolf, Roland C.
A1  - Elcombe, Clifford R.
A1  - Schwarz, Michael
A1  - Moulin, Pierre
A1  - Terranova, Rémi
A1  - Moggs, Jonathan G.
T1  - Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion
JF  - Toxicological Sciences
N2  - The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
Y1  - 2012
U6  - http://dx.doi.org/10.1093/toxsci/kfs303
SN  - 1094-2025
VL  - 131
IS  - 2
SP  - 375
EP  - 386
PB  - Oxford University Press
CY  - Oxford
ER  - 
TY  - CHAP
A1  - Henderson, Colin J.
A1  - Wolf, C. Roland
A1  - Scheer, Nico
ED  - Woolf, Thomas F.
T1  - The use of transgenic animals to study drug metabolism
T2  - Handbook of Drug Metabolism. 2nd Edition
Y1  - 2009
SN  - 978-1-4200-7647-9
SP  - 637
EP  - 658
PB  - Informa Healthcare
CY  - New York
ER  - 
TY  - CHAP
A1  - Wolf, C. Roland
A1  - Kapelyukh, Yury
A1  - Scheer, Nico
A1  - Henderson, Colin J.
ED  - Wilson, Alan G. E.
T1  - Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs
N2  - The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic.
Y1  - 2015
SN  - 978-1-78262-778-4
U6  - http://dx.doi.org/10.1039/9781782622376-00152
SP  - 152
EP  - 176
PB  - RSC Publ.
CY  - Cambridge
ER  - 
TY  - CHAP
A1  - Scheer, Nico
A1  - Chu, Xiaoyan
A1  - Salphati, Laurent
A1  - Zamek-Gliszczynski, Maciej J.
ED  - Nicholls, Glynis
T1  - Knockout and humanized animal models to study membrane transporters in drug development
T2  - Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development
Y1  - 2016
SN  - 978-1-78262-379-3
U6  - http://dx.doi.org/10.1039/9781782623793-00298
SP  - 298
EP  - 332
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - CHAP
A1  - Samuelsson, K.
A1  - Scheer, Nico
A1  - Wilson, I.
A1  - Wolf, C.R.
A1  - Henderson, C.J.
ED  - Chackalamannil, Samuel
T1  - Genetically Humanized Animal Models
T2  - Comprehensive Medicinal Chemistry III. 3rd Edition
N2  - Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.
KW  - Chimeric liver-humanized mice
KW  - Drug distribution
KW  - Drug metabolism
KW  - Toxicology
KW  - Knockout mice
Y1  - 2017
SN  - 978-0-12-803201-5
U6  - http://dx.doi.org/10.1016/B978-0-12-409547-2.12376-5
SP  - 130
EP  - 149
PB  - Elsevier
CY  - Saint Louis
ER  - 
TY  - JOUR
A1  - Stanley, Lesley A.
A1  - Horsburgh, Brian C.
A1  - Ross, Jillian
A1  - Scheer, Nico
A1  - Wolf, C. Roland
T1  - Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity
JF  - Drug Metabolism Reviews
Y1  - 2006
U6  - http://dx.doi.org/10.1080/03602530600786232
SN  - 1097-9883
VL  - 38
IS  - 3
SP  - 515
EP  - 597
ER  - 
TY  - JOUR
A1  - Stanley, Lesley A.
A1  - Horsburgh, Brian C.
A1  - Ross, Jillian
A1  - Scheer, Nico
A1  - Wolf, C. Roland
T1  - Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior
JF  - Drug Metabolism Reviews
Y1  - 2009
U6  - http://dx.doi.org/10.1080/03602530802605040
SN  - 1097-9883
VL  - 41
IS  - 1
SP  - 27
EP  - 65
PB  - Taylor & Francis
CY  - London
ER  - 
TY  - JOUR
A1  - Henderson, Colin J.
A1  - Scheer, Nico
A1  - Wolf, C. Roland
T1  - Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man
JF  - Expert Review of Clinical Pharmacology
Y1  - 2009
U6  - http://dx.doi.org/10.1586/17512433.2.2.105
SN  - 1751-2441
VL  - 2
IS  - 2
SP  - 105
EP  - 109
PB  - Taylor & Francis
CY  - London
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Wolf, C. Roland
T1  - Xenobiotic receptor humanized mice and their utility
JF  - Drug Metabolism Reviews
Y1  - 2013
U6  - http://dx.doi.org/10.3109/03602532.2012.738687
SN  - 1097-9883
IS  - 1
SP  - 110
EP  - 121
PB  - Taylor & Francis
CY  - London
ER  -