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The effects of interleukin-6 in a rat model of hepatocellular carcinoma

Moran, Diarmuid Martin (2005) The effects of interleukin-6 in a rat model of hepatocellular carcinoma. PhD thesis, Dublin City University.

Interleukin-6 (IL-6) is integrally linked to normal hepatic growth and liver regeneration. The aim of the present study was to determine the expression and function of IL-6 signalling pathways m a rat model of hepatocellular carcinoma (HCC). In these studies HCC was charactensed by dysregulated expression of IL-6 signalling components in vivo and in vitro, including downregulated expression of the IL-6 receptor and increased IL-6 production and secretion. Recombinant human IL-6 (rhIL-6) treatment of isolated rat HCC cells and hepatocytes in vitro led to the activation of janus kinase-signal transducer and activator of transcription (Jak-STAT) and Ras-mitogen activated protein kinase intracellular signalling pathways Cyclin dependent kinase (cdk) inhibitor expression was increased m HCC cells after treatment with IL-6, an effect that was not observed in isolated hepatocytes. Decreases in cdk activity after rhIL-6 treatment result in a G0/G1 growth arrest in HCC cells. As a result of these in vitro studies, an algmate based cell microencapsulation system was developed to provide continual in vivo rhIL-6 delivery in a rat model of HCC CHO cells transfected to supra-express rhIL-6 were encapsulated in algmate and implanted in HCC tumour burdened rats resulting in high serum levels of biologically active rhIL-6 Recombinant human IL-6 was detected in both normal and tumour liver tissues resulting in activation of the Jak-STAT pathway. Due to tumour volume variability, no conclusions on the effects of rhIL-6 on tumour progression in vivo could be determined However, rhIL-6 treatment did result in increased total hepatic weight. Collectively this study demonstrates a role for IL-6 m HCC progression and identifies algmate encapsulated CHO cells as an effective method for rhIL-6 delivery in vivo which has potential in the study of normal and abnormal liver growth.
Item Type:Thesis (PhD)
Date of Award:2005
Supervisor(s):Cahill, Paul and McKillop, Iain H.
Uncontrolled Keywords:Hepatic growth; Tumour growth; Hepatocellular carcinoma
Subjects:Biological Sciences > Biotechnology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
ID Code:18084
Deposited On:09 May 2013 10:02 by Celine Campbell . Last Modified 09 May 2013 10:02

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