Imperial College London

ProfessorEricAboagye

Faculty of MedicineDepartment of Surgery & Cancer

Professor
 
 
 
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Contact

 

+44 (0)20 3313 3759eric.aboagye

 
 
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Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
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Location

 

GN1Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Trousil:2019:10.1111/bph.14776,
author = {Trousil, S and Lee, P and Edwards, RJ and Maslen, L and Lozan-Kuehne, JP and Ramaswami, R and Aboagye, EO and Clarke, S and Liddle, C and Sharma, R},
doi = {10.1111/bph.14776},
journal = {British Journal of Pharmacology},
pages = {3712--3722},
title = {Altered cytochrome 2E1 and 3A P450-dependent drug metabolism in advanced ovarian cancer correlates to tumour-associated inflammation},
url = {http://dx.doi.org/10.1111/bph.14776},
volume = {176},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background and PurposePrevious work has focussed on changes in drug metabolism caused by altered activity of CYP3A in the presence of inflammation and, in particular, inflammation associated with malignancy. However, drug metabolism involves a number of other P450s, and therefore, we assessed the effect of cancerrelated inflammation on multiple CYP enzymes using a validated drug cocktail.Experimental ApproachPatients with advanced stage ovarian cancer and healthy volunteers were recruited. Participants received caffeine, chlorzoxazone, dextromethorphan, and omeprazole as in vivo probes for CYP1A2, CYP2E1, CYP2D6, CYP3A, and CYP2C19. Blood was collected for serum Creactive protein and cytokine analysis.Key ResultsCYP2E1 activity was markedly upregulated in cancer (6hydroxychlorzoxazone/chlorzoxazone ratio of 1.30 vs. 2.75), while CYP3A phenotypic activity was repressed in cancer (omeprazole sulfone/omeprazole ratio of 0.23 vs. 0.49). Increased activity of CYP2E1 was associated with raised serum levels of IL6, IL8, and TNFα. Repression of CYP3A correlated with raised levels of serum Creactive protein, IL6, IL8, and TNFα.Conclusions and ImplicationsCYP enzyme activity is differentially affected by the presence of tumourassociated inflammation, affecting particularly CYP2E1 and CYP3Amediated drug metabolism, and may have profound implications for drug development and prescribing in oncological settings.
AU - Trousil,S
AU - Lee,P
AU - Edwards,RJ
AU - Maslen,L
AU - Lozan-Kuehne,JP
AU - Ramaswami,R
AU - Aboagye,EO
AU - Clarke,S
AU - Liddle,C
AU - Sharma,R
DO - 10.1111/bph.14776
EP - 3722
PY - 2019///
SN - 0007-1188
SP - 3712
TI - Altered cytochrome 2E1 and 3A P450-dependent drug metabolism in advanced ovarian cancer correlates to tumour-associated inflammation
T2 - British Journal of Pharmacology
UR - http://dx.doi.org/10.1111/bph.14776
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000478835200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/73196
VL - 176
ER -