Calcium Signalling Group

Calcium Signalling Research Group

Calcium Signalling Research Group Head: Professor Greg Barritt
Phone: +61 8 8204 4260
Email: greg.barritt@flinders.edu.au
Publications

Current Research Focus

Amongst the Calcium Signalling Research Group's pool of works are projects with a focus on liver cancer and calcium expression:

Surgical treatment of liver cancer

Liver surgery and transplantation for liver cancers are often associated with damage to the liver, leading to slow recovery and sometimes to death. This damage is often greater in obese patients.

Rapamycin, which suppresses the immune system and inhibits cancer growth, is often administered to liver transplant patients. However, its use is controversial since it has both beneficial and detrimental effects.

The aim of this research is to better understand the mechanisms of action of rapamycin on the liver.

Rapamycin and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) and metastatic cancer of the liver can only presently be treated by surgical liver resection or liver transplantation. These surgical procedures often result in reduced liver function through ischemia reperfusion (IR) injury.

Tumour recurrence is a major concern in surgery for liver cancer.

Rapamycin, an immunosuppressant currently employed in the management of liver transplant patients, inhibits the growth of cancer cells and has been used clinically to inhibit tumour cell regrowth. However, the clinical use of rapamycin is somewhat controversial since it also has the potential to enhance cell proliferation and hence cancer cell re-growth. Thus it is important to fully understand the effects of rapamycin in the liver and the intracellular mechanisms involved.

Recent studies have shown that rapamycin can induce the synthesis in the liver of two important antioxidant enzymes, heme oxygenase 1 (HO-1) and peroxiredoxin 1 (Prx-1). However, this is associated with the inhibition of bile flow recovery in the acute phase of ischemia reperfusion (IR).

The overall aims of this research are to gain a better understanding of the actions of rapamycin on the liver. The specific aims are to test the following hypotheses concerning the actions of rapamycin on the liver.

  • That rapamycin inhibits the expression of bile acid transporters.
  • That the mechanism by which rapamycin induces the expression of heme oxygenase-1 and peroxiredoxin-1 and inhibits expression of bile acid transporters involves phosphatidyl inositol-3-kinase, Akt and transcription factor Nrf2. HCC, metastatic liver cancer, and IR injury following liver resection and transplantation to treat these diseases are responsible for substantial morbidity and mortality, especially in obese and aged patients. The results of this research should ultimately contribute to (i) a better understanding of the mechanisms of action of rapamycin on the liver and hence to improvements in the use of this drug in the treatment of patients with liver cancer and (ii) improved outcomes (longer survival with a better quality of life) for patients undergoing liver resection or transplantation for the treatment of liver cancer.