Novel Strategies In Cancer Cell Invasion In High-density 3D Matrix
Funder
National Health and Medical Research Council
Funding Amount
$60,768.00
Summary
The use of high-density (HD) matrix to study cell invasion sets precedence in mimicking the HD breast tissue condition that pose a real cancer risk. Cell invasion promotes the spread of cancer causing organ failures and death. The aims of this project are to determine the molecular mechanisms and to isolate new regulatory markers of cell invasion into HD matrix. Putative markers will be confirmed by investigating their expression levels in tissue arrays of 195 breast cancer samples.
Apportioning Deficits In Bone Size And Density In Women With Fractures To Growth Or Ageing By Studies In Their Daughters
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Women fracture their bones because the bones are small and break easily and because the bones are thin or low in denseness (very porous like a honey comb). This study is aimed at identifying why women with fractures have small bones and why the bones are so porous. They may have these problems because they lost a lot of bone as they get older or because growth was abnormal so the size of the bone didn't reach its potential size or because the denseness of the bones didn't develop properly. The s ....Women fracture their bones because the bones are small and break easily and because the bones are thin or low in denseness (very porous like a honey comb). This study is aimed at identifying why women with fractures have small bones and why the bones are so porous. They may have these problems because they lost a lot of bone as they get older or because growth was abnormal so the size of the bone didn't reach its potential size or because the denseness of the bones didn't develop properly. The study will be carried out in women with spine or hip fractures and their daughters. All participants will have bone densitometry, provide a 24 hour urine sample and a fasting blood sample of 20 ml whole blood. Informed consent will be obtained from all participants. The bone density scan is associated with radiation exposure of about 4 mSv, about one tenth of a chest x ray, temporary bruising may follow taking blood. If we can understand the different ways osteoporosis can occur we can then start to devise specific treatments tailored to the individual. Also if we can identify the causes of small bones and bone thinness during growth it may be possible to correct some of these causes before the reduced growth and reduced building of bone occurs. We might also prevent the thinning of bone by identifying and removing causes of bone thinning.Read moreRead less
Suppression Of NADPH Oxidase-derived Oxidative Stress By Anti-sense Probes And HDL In Human Vascular Endothelium
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) develo ....In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) developed in our laboratory, which block a particular gene causing oxidative stress, we will determine whether this gene is responsible for the formation of oxyradicals in human and mouse cells grown in culture. In addition, we will explore whether this gene is turned on by factors known to be involved in CHD. Finally, we will also investigate whether the good cholesterol known as HDL can act to prevent oxidative stress in human cells, as we discovered it appears to do in living arteries in vivo. If we find it has the same protective effect in endothelium, we will determine how it does this, and which component proteins of the HDL particle are important. This might suggest new treatments to prevent acute events leading to heart attack and stroke, and possibly new applications where damage appears to result from acute oxidative stress, such as in the brain soon after a stroke has occurred. We also have a plan to develop antisense drugs that will target the important gene specifically in the affected endothelium. In addition, we have other specific new drugs that will block this system in arteries. Simultaneously we will be testing the role of this gene in mouse and rabbit models of artery disease, for both our types of drugs might provide valuable new therapeutic agents to target the underlying cause of CHD and not just its symptoms as current drugs do.Read moreRead less
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.