Document Detail


Bevacizumab impairs hepatocyte proliferation after partial hepatectomy in a rabbit model.
MedLine Citation:
PMID:  23225416     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Bevacizumab is used to treat patients with metastatic colorectal cancer, including those who will undergo liver surgery. The effects of this agent on the regenerative capacity of the liver are unclear. We used a rabbit model of partial hepatectomy to assess the effects of bevacizumab on hepatocyte replication and the expression of genes relevant to angiogenesis and proliferation.
MATERIALS AND METHODS: Thirty rabbits underwent 28% hepatectomy. At the end of the procedure, animals were blindly randomized into two groups. A control group was injected i.v. with saline and the other group with bevacizumab at 50 mg/kg. Three rabbits from each group were sacrificed at days 2, 3, 5, 7 and 14 after hepatectomy. Livers were collected and processed. Hepatocyte proliferation was evaluated by Ki-67 immunostaining and apoptosis by caspase-3 activity. Gene expression of Vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF) and Inhibitor α of nuclear factor-κB (IκBα) was determined by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR).
RESULTS: Compared with controls, hepatocyte proliferation in bevacizumab-treated animals was decreased 1.8-fold at day 3, 1.6-fold at day 5 and 2.1-fold at day 14. Neoangiogenesis began after day 5, with a peak of VEGF mRNA evident at day 7 in both groups. Expression of IκBα, a transcriptional target of Nuclear Factor-κB, increased significantly from baseline only in the control group: at day 2, expression was 179% of the day 0 value in controls versus 112% in the bevacizumab group. Expression of HGF and caspase-3 was similar in the two groups and remained stable over time.
CONCLUSION: A single i.v. injection of bevacizumab impaired hepatocyte proliferation in a rabbit model of partial hepatectomy.
Authors:
Aurelien Dupre; Andrea Paradisi; Stephan Langonnet; Alessandro Gandini; Patrick Mehlen; Michel Rivoire
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-05-02     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  5193-200     Citation Subset:  IM    
Affiliation:
Department of Surgical Oncology, Léon Bérard Centre, 28 rue Laennec, 69008 Lyon, France. dupre.aurelien@hotmail.fr
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / blood
Angiogenesis Inhibitors / pharmacology
Animals
Antibodies, Monoclonal, Humanized / pharmacology*
Apoptosis / drug effects
Aspartate Aminotransferases / blood
Cell Proliferation / drug effects
Female
Hepatectomy
Hepatocyte Growth Factor / biosynthesis,  genetics
Hepatocytes / cytology,  drug effects*
I-kappa B Proteins / biosynthesis,  genetics
Liver Regeneration / drug effects*
RNA, Messenger / biosynthesis,  genetics
Rabbits
Random Allocation
Vascular Endothelial Growth Factor A / biosynthesis,  genetics
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 0/I-kappa B Proteins; 0/RNA, Messenger; 0/Vascular Endothelial Growth Factor A; 139874-52-5/NF-kappaB inhibitor alpha; 2S9ZZM9Q9V/bevacizumab; 67256-21-7/Hepatocyte Growth Factor; EC 2.6.1.1/Aspartate Aminotransferases; EC 2.6.1.2/Alanine Transaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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