Mouse models of liver cancer

Summary

This project will use mouse models to investigate the role of adiponectin and T-cadherin in models of liver cancer.

Supervisor(s)

Dr Lionel Hebbard, Dr Liang Qiao

Research Location

Westmead - Westmead Institute for Medical Research

Program Type

PHD

Synopsis

There is increasing evidence that adiponectin is involved in liver cancer. 1. Adiponectin and one of its receptors T-cadherin are expressed on liver cancer blood vessels. 2. Obese or overweight individuals have reduced serum levels of adiponectin and increased risk of liver cancer. This risk is compounded in individuals who have metabolic syndrome and hepatitis. 3. Adiponectin and T-cadherin have been shown to be important in regulating other cancers. Our studies concern liver cancer, the third leading cause of cancer deaths worldwide. Data from the NSW Public Health Bulletin (2001) indicates that the annual change in incidence and mortality from cancers in both genders between 1987 and 1997 was highest for liver cancer (~8% pa), compared to all other malignancies and accounts for approximately 1000 deaths in Australia annually. Despite advances in early diagnosis and surgical techniques however, the mortality from liver cancer is unacceptably high with 5 year survival rates below 20%. Recent data indicate that up to a third of future liver cancer in developed countries will be a consequence of fatty liver disease, while even in persons with chronic viral hepatitis, the risk of cancer is increased over 100-fold in the presence of obesity and diabetes. Thus, the overall objective of this proposal is to investigate the mechanisms that drive liver cancer progression in persons who are overweight or obese (currently over 60% of the Australian population). To this end, we will specifically examine the role of the adipocyte-derived hormone adiponectin (a key mediator of metabolic dysregulation in the metabolic syndrome), and one of its receptors, T-cadherin in regulating HCC. Techniques used in this project: * Mouse models, primary cell isolation. * Histology, confocal microscopy. * PCR, gene cloning. * Recombinant protein expression. * Adenovirus generation. * Protein analysis (SDS-PAGE, Western Blotting). * In vitro assays of primary liver non-parenchymal cells.

Additional Information

http://www.wmi.usyd.edu.au/research/storrliver.htm

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Keywords

Liver, Cancer Cell, Signalling, metabolism

Opportunity ID

The opportunity ID for this research opportunity is: 860

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