Molecular Determinants Of Advanced Disease In Ovarian Granulosa Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$612,244.00
Summary
Granulosa cell tumours of the ovary (GCT) represent 5-10% of malignant ovarian cancers. They are distinct from the more common epithelial tumours and although considered to have a much better prognosis, they have a propensity to late recurrence. Recurrent or aggressive GCT have a poor prognosis. These studies will investigate the molecular basis of recurrence and aggressive behaviour in GCT. This will provide both prognostic information and also potential therapeutic targets.
Prediction Of Adverse Outcomes Following A Fragility Fracture
Funder
National Health and Medical Research Council
Funding Amount
$148,426.00
Summary
Individuals with an existing fracture are at increased risk of adverse outcomes such as re-fracture and premature mortality, but it is not clear why. We propose to evaluate risk factors, and prognostic models, for predicting the risk of adverse outcomes. We also propose to develop a quantitative risk-benefit framework for evaluating the clinical utility of such prognostic models and help ensure that therapies appropriately address real-life experience of osteoporotic patients.
Sex Hormones And Heart Disease In Older Women Study (The SHOW Study)
Funder
National Health and Medical Research Council
Funding Amount
$594,672.00
Summary
Cardiovascular disease (CVD, heart disease and stroke) is the leading cause of death in women aged 65 and over. Counter-intuitively, androgens may be as, or even more important, than estrogens in determining CVD risk and all-cause mortality in women, but this is yet to be verified. We will document blood levels of androgens in women aged 70+ and determine whether androgens are associated with CVD and death in this large cohort of elderly well women.
Type 2 diabetes represents an escalating global health problem. In Australia 7.2% of the population has diabetes but an additional 16% have difficulty handling glucose, a problem which frequently precedes the development of diabetes. Resistance of tissues to the action of insulin is an essential pre-requisite for type 2 diabetes but is also closely associated with the syndrome of obesity, dyslipidaemia, hypertension and cardiovascular diseases (Syndrome X). Genetic factors combined with a high c ....Type 2 diabetes represents an escalating global health problem. In Australia 7.2% of the population has diabetes but an additional 16% have difficulty handling glucose, a problem which frequently precedes the development of diabetes. Resistance of tissues to the action of insulin is an essential pre-requisite for type 2 diabetes but is also closely associated with the syndrome of obesity, dyslipidaemia, hypertension and cardiovascular diseases (Syndrome X). Genetic factors combined with a high caloric intake and a sedentary lifestyle are together responsible for the development of insulin resistance. From evidence that we and others have obtained in recent years it is evident that an important mediator of insulin resistance is the amount of fat which accumulates in muscle and liver. One way in which this abnormality seems to cause insulin resistance is through interference with the normal signalling mechanism which causes increased glucose metabolism in response to insulin. While experiments in cell systems have identified some candidate molecules that may be involved, a need exists to demonstrate whether their dysregulation actually causes the insulin resistance in the whole animal or human, or are merely associated with it. We will use novel techniques to manipulate the levels of one of these candidate genes, protein kinase B-Akt, and its regulators in the muscle of rodents. We will then examine the effects of these manipulations on insulin resistance using a combination of metabolic and molecular tests. Building upon earlier work we will also determine how important different subtypes of this molecule are for both normal and abnormal insulin-glucose metabolism, and whether these molecules or others in the pathway are more important in insulin resistance. This knowledge will be invaluable in tailoring specific novel treatment strategies or drugs for prevention or treatment of insulin resistance, and thus reducing the burden of type 2 diabetes and Syndrome X.Read moreRead less
Type 2 Diabetic Renal Complications And Microvascular Injury: Novel Predictors Of Onset And Progression, Mechanisms Of Association With Cardiovascular Disease And The Benefits Of Fenofibrate.
Funder
National Health and Medical Research Council
Funding Amount
$84,448.00
Summary
We will investigate the mechanisms of diabetic complications related to kidney and blood vessel disease, focusing on identifying people at greater risk and ways to improve or prevent these complications. In addition, we will look at how diabetic kidney disease affects non-kidney related problems like heart disease and examine the benefit of fenofibrate on both. This greater understanding will aid further drug development in kidney and cardiovascular diseases.
GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
Clinically Severe Obesity: A Better Understanding Of A Complex Condition, Improving Health Outcomes Through Effective Therapies, And Delivering A Comprehensive Clinical Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$701,539.00
Summary
Clinically severe obesity impacts on the health of 7-8% or 1.5 million Australians, yet poor access to integrated effective care. This challenging area of healthcare is distorted by perceptions and beliefs that are frequently contrary to clinical and physiological research findings. Professor Dixon’s plan is to: 1) To learn more about clinically severe obesity, 2) improve the assessment and delivery of effective care, and 3) improve clinical capacity to better care for these Australians.