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The potential contribution of tumour-related factors to the development of FOLFOX-induced sinusoidal obstruction syndrome

Lookup NU author(s): Stuart Robinson, Professor Derek Mann, Professor Derek Manas, Professor Fiona Oakley, Professor Jelena Mann, Steven White

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Abstract

Background: Chemotherapy-associated liver injury (CALI) has been linked to increased morbidity and poorer disease-specific outcomes in patients undergoing resection of colorectal liver metastases (CRLM). The aim of this study was to assess the contribution of tumour-related factors to the development of FOLFOX-induced liver injury.Methods: We assessed the effect of FOLFOX treatment on the murine liver either in the presence or absence of CRLM to evaluate the contribution of both chemotherapy and tumour death to the development of CALI.Results: In the presence of liver metastases, there was increased hepatic expression of plasminogen activator inhibitor-1 (146-fold; P < 0.01) and vWF (2.4-fold; P < 0.01) transcript as compared with sham-operated controls. In addition, we detected large clusters of megakaryocytes in the spleen of FOLFOX-treated tumour-bearing animals. The livers of FOLFOX-treated animals also showed changes in matrix remodelling genes such as TGF beta (P < 0.01), MMP2 (P < 0.001), TIMP1 (P < 0.001) and Pro-Collagen I (P < 0.05) which was exacerbated in the presence of tumour. These genes have previously been demonstrated to have a key role in FOLFOX-induced liver injury.Conclusion: It appears that the toxicity of FOLFOX chemotherapy is enhanced by tumour-related factors.


Publication metadata

Author(s): Robinson SM, Mann DA, Manas DM, Oakley F, Mann J, White SA

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2013

Volume: 109

Issue: 9

Pages: 2396-2403

Print publication date: 29/10/2013

Online publication date: 10/10/2013

Acceptance date: 12/09/2013

Date deposited: 02/12/2014

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/bjc.2013.604

DOI: 10.1038/bjc.2013.604


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