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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2017; 23(30): 5499-5507
Published online Aug 14, 2017. doi: 10.3748/wjg.v23.i30.5499
Published online Aug 14, 2017. doi: 10.3748/wjg.v23.i30.5499
Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease
Frederik Temmerman, Ingrid Vander Elst, Petra Windmolders, Frederik Nevens, Jos van Pelt, Laboratory of Hepatology, Department of Clinical and Experimental Medicine, Faculty of Medicine, University of Leuven, B 3000 Leuven, Belgium
Frederik Temmerman, Ingrid Vander Elst, Petra Windmolders, Frederik Nevens, Jos van Pelt, Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, B 3000 Leuven, Belgium
Feng Chen, Department of Radiology, The first Affiliated Hospital School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Louis Libbrecht, Department of Pathology, Ghent University Hospital, B 9000 Ghent, Belgium
Yuanbo Feng, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, KU Leuven, B 3000 Leuven, Belgium
Humbert De Smedt, Laboratory of Molecular and Cellular Signalling, KU Leuven, B 3000 Leuven, Belgium
Jos van Pelt, Unit of Clinical Digestive Oncology, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, B 3000 Leuven, Belgium
Author contributions: Temmerman F performed the majority of experiments; Chen F, Feng Y and Ni Y performed the MRI and liver volume calculations; Libbrecht L performed histological interpretation; Vander Elst I and Windmolders P assisted with the animal experiments, performed molecular and protein analysis and processed tissue for histology; De Smedt H assisted in protein data analysis; Temmerman F, Nevens F and van Pelt J designed and coordinated the research, analyzed the data and wrote the paper.
Institutional animal care and use committee statement: All animal experiments were approved by the Ethical Committee for animal welfare (KU Leuven, P164/2010).
Conflict-of-interest statement: None of the authors report a potential conflict of interest regarding this work.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Jos van Pelt, Professor, Laboratory of Hepatology, Department of Clinical and Experimental Medicine, Faculty of Medicine, University of Leuven, Geb. Onderwijs and Navorsing 1, 7e verd, bus 703, Herestraat 49, B 3000 Leuven, Belgium. jos.vanpelt@kuleuven.be
Telephone: +32-16-330694 Fax: +32-16-330701
Received: February 27, 2017
Peer-review started: March 2, 2017
First decision: April 5, 2017
Revised: May 16, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: August 14, 2017
Processing time: 167 Days and 10.6 Hours
Peer-review started: March 2, 2017
First decision: April 5, 2017
Revised: May 16, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: August 14, 2017
Processing time: 167 Days and 10.6 Hours
Core Tip
Core tip: The continuous increase of liver cysts volume in polycystic-liver-disease (PCLD) leads to extensive hepatomegaly and portal hypertension, an indication for liver transplantation. The effect of mTOR-inhibition on liver volume (LV) in PCLD is unclear. We developed an accurate, non-invasive, MRI-based method to determine LV in a PCLD rat model. When treatment is started at the moment of extensive hepatomegaly (as in humans), the mTOR inhibitor everolimus halt disease progression and also of the development of fibrosis in this model. We speculate that everolimus, given after kidney transplantation in patients with PCLD, can prevent the development of symptomatic hepatomegaly.