Novel Tools For The Imaging Of Tumor Hypoxia Using PET
Funder
National Health and Medical Research Council
Funding Amount
$727,856.00
Summary
Fast growing tumors often outgrow the ability of blood vessels to properly supply them with nutrients and oxygen. This creates tissue areas within the tumor that are lacking oxygen and are highly resistant to radiotherapy and chemotherapy. Imaging these areas using nuclear medicine techniques has now become important for therapy planning of cancer sufferers. This project aims to improve the properties of the existing agents in order to better select patients for a particular type of treatment.
Hepatocellular carcinoma (HCC), or liver cancer, is a major global problem. Most people present with advanced disease and current therapies are relatively ineffective. Small RNAs, called microRNAs are a new form of therapy that may present new options for patients with HCC. We have characterised a microRNA that is a powerful inhibitor of HCC growth both in cells and in preclinical animal models. This project will characterise the microRNA’s function in HCC and as a potential therapeutic.
E2F Inhibitors As Anticancer Agents For Squamous Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour de ....Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour development. In normal cells, E2F1 is required for the regulated growth of head and neck cells. However, we found that in head and neck tumours, E2F1 is overactive and contributes to the dergulated growth of the tumour. In this project we will test our newly developed inhibitors of E2F1 on various tumour cells derived from head and neck cancers to see how effective they are at stopping tumour cell growth. Furthermore we will test these compounds in animal models of head and neck cancer to determine whether they will be useful therapeutic agents for treatment of human cancer. Early results on tumour cell lines look very promising.Read moreRead less
The Mechanism Of Action Of Progastrins In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$378,000.00
Summary
Clear evidence now links precursors of the hormone gastrin with the development of colorectal cancer (CRC). Elevated gastrin concentrations in the blood increase the risk of developing CRC, and in patients with CRC blood gastrin concentrations are higher than normal. Furthermore experiments in animals indicate that gastrin precursors stimulate growth of the cells lining the interior of the colon. The major challenges in this field are to characterise the proteins (called receptors) which bind ga ....Clear evidence now links precursors of the hormone gastrin with the development of colorectal cancer (CRC). Elevated gastrin concentrations in the blood increase the risk of developing CRC, and in patients with CRC blood gastrin concentrations are higher than normal. Furthermore experiments in animals indicate that gastrin precursors stimulate growth of the cells lining the interior of the colon. The major challenges in this field are to characterise the proteins (called receptors) which bind gastrin precursors to the surface of colon cells, and to understand how receptor binding triggers changes in the colon which result in CRC development. Our recent discovery that gastrin precursors promote cell migration by reducing adhesion between cells is particularly significant from the perspective of CRC because of the potential importance of this phenomenon in the early stages of cancer development. Our recent observation that gastrin precursors bind metal ions with high affinity further suggests that metal binding may be essential for receptor binding and hence for biological activity. We will therefore investigate: (1) whether binding of metal ions to gastrin precursors effects biological activity, (2) which regions of gastrin precursors are required for receptor binding, (3) the structures of the receptors which bind gastrin precursors to colon cells, (4) the pathways which connect the receptors to other intracellular proteins that maintain contact between adjacent cells, and (5) the differences between the pathways controlling adhesion and the pathways controlling cell growth. This project should lead to a detailed understanding of the molecular mechanisms underlying the effect of gastrin precursors on colon cell growth and adhesion. Definition of the receptors and intracellular signalling mechanisms involved may ultimately lead to novel treatments for disorders of colonic proliferation including CRC.Read moreRead less
Investigation Into Oral Cancer In Non-drinking And Non-smoking Females
Funder
National Health and Medical Research Council
Funding Amount
$109,358.00
Summary
There has been an increase incidence of oral cancer in female non-drinkers, non-smokers. The five year survival following diagnosis can be as low as 15-50% as most cancers are advanced at the time of discovery.Precancerous and cancerous oral lesions may mimic any number of benign oral lesions, and as such may be left without investigation and treatment until well advanced. Further investigations into the cause of oral cancer other than smoking and alcohol will aid in management.
Regulation Of Gastric Tumour Invasion And Growth By Gp130 Activating Cytokines.
Funder
National Health and Medical Research Council
Funding Amount
$625,642.00
Summary
Gastric cancer is a major cause of morbidity and death worldwide. We have previously established a very informative animal model of this disease which has facilitated a new understanding of the diverse role of the IL-6 family of cytokines in regulating gastric tumour growth and dissemination to distant organs. This proposal will focus on how the main members of this cytokine family, namely IL-6 and IL-11, inhibit gastric tumour invasion to other organs, and promote tumour growth respectively . A ....Gastric cancer is a major cause of morbidity and death worldwide. We have previously established a very informative animal model of this disease which has facilitated a new understanding of the diverse role of the IL-6 family of cytokines in regulating gastric tumour growth and dissemination to distant organs. This proposal will focus on how the main members of this cytokine family, namely IL-6 and IL-11, inhibit gastric tumour invasion to other organs, and promote tumour growth respectively . An understanding of these processes will aid in designing therapeutic interventions specific for each cytokine and which may lead to drugs aimed at limiting or reversing this disease.Read moreRead less
Skin cancer affects 60% of Australians. Nicotinamide (vitamin B3) prevents many of sunlight’s damaging effects and reduces premalignant keratoses by 35% compared to placebo in sun-damaged individuals. We now need to test whether nicotinamide can prevent skin cancer. Skin cancer patients will receive nicotinamide or placebo for 12 months and new cancers will be counted in each group. Nicotinamide is safe, widely available and an exciting opportunity for cost-effective skin cancer prevention.