Therapeutic Targeting Of The Hedgehog Signaling Pathway In Premalignant Lesions Of The Breast.
Funder
National Health and Medical Research Council
Funding Amount
$115,980.00
Summary
Breast screening has been successful in reducing deaths from breast cancer. Unfortunately it also detects increasing numbers of precancerous changes. Treatment of these changes is often aggressive, using surgery and radiotherapy. However we are unable to predict exactly which of the changes we need to treat. We aim to better understand the changes involved in this progression and try to block them using new drugs.
What Factors Affect Lesion Distribution In Multiple Sclerosis And Experimental Autoimmune Encephalomyelitis?
Funder
National Health and Medical Research Council
Funding Amount
$56,797.00
Summary
Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be m ....Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be much more susceptible to this attack than others, and the question that this study will address is why do lesions occur where they do in MS? Some preliminary results strongly suggest that there is a link between carrying particular genes that control immune responses, having immune cells that can attack one particular protein in the nervous system called PLP, and developing lesions in parts of the brain that control balance. This will be investigated further, and we will also look for other links between immune cells that can attack other proteins and development of lesions in particular areas. If such links can be identified, they would be very important for improved diagnosis of MS and it would enable more specific treatments for MS to be developed. We will also use experimental models of MS to investigate the exact components within the nervous system and within the immune system that play a role in directing the attack to particular sites.Read moreRead less
RISK AND PROTECTION FACTORS FOR NORMAL AND ABNORMAL BRAIN AGEING: A LONGITUDINAL EPIDEMIOLOGICAL MRI STUDY
Funder
National Health and Medical Research Council
Funding Amount
$153,020.00
Summary
Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed u ....Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed up at 4-yearly intervals for 20 years. The focus of the study is on neuropsychiatric disorders (anxiety, depression, substance use and cognitive disorders). In this application, we propose to perform MRI scans and blood tests on a quarter (n-500) of the 60-64 sample to obtain an epidemiological sample for brain morphology. Not only will we be able to study changes in brain morphology over time, and relate it with cognitive function and psychiatric disorder, we will also be able to assess the role of risk and protection factors. We are particularly interested in brain reserve, dietary factors (anti-oxidants, omega 3, wine and folate) and drugs (anti-inflammatory drugs, hormone replacement and vitamin supplements) as protection factors, and hypertension, homocysteine levels, white matter lesions on MRI and low hippocampal volumes as risk factors for cognitive impairment and dementia. We also want to study the brain morphological correlates of Depression in a community sample. The study will enhance our understanding of the ageing brain, both in health and disease, and identify factors that increase or decrease the risk of cognitive impairment and psychiatric disorder in old age.Read moreRead less
Characterisation Of Precursor Lesions In Colorectal Cancers With DNA Instability
Funder
National Health and Medical Research Council
Funding Amount
$60,190.00
Summary
It is now generally accepted that most colorectal cancers arise from previously benign lesions in the mucosal lining of the large bowel. These lesions are called adenomatous polyps. They have been extensively studied as have the cancers which evolve from them with regard to the type of cancer causing genetic changes they bear. Recently, it has been found that colorectal cancer is not a single disease in that there exists a subgroup comprising 15% of colorectal cancers which is an entirely differ ....It is now generally accepted that most colorectal cancers arise from previously benign lesions in the mucosal lining of the large bowel. These lesions are called adenomatous polyps. They have been extensively studied as have the cancers which evolve from them with regard to the type of cancer causing genetic changes they bear. Recently, it has been found that colorectal cancer is not a single disease in that there exists a subgroup comprising 15% of colorectal cancers which is an entirely different type wwith respect to genetic changes and biological behaviour. This subgroup contains cancers with a high level of microsatellite instability (MSI-high) and the cancers which comprise this group show none of the common genetic changes which can be demonstrated in both adenomatous polyps and the 85% of colon cancers which develop from them. The MSI-high colorectal cancers do however share some striking similarities to a type of polyp (hyperplastic) which has until quite recently been considered of little consequence. Our research group and others have shown an association with colorectal cancer in those patients in whom hyperplastic polyps are unusually large or numerous, especially if present in the right side of the large bowel, where the bulk of MSI-high colorectal cancers arise. The current proposal will investigate the hyperplastic polyp as a precursor lesion in the genesis of MSI-high cancers.Read moreRead less
Plasticity Of Sensorimotor Representations In Adult Primate Cortex
Funder
National Health and Medical Research Council
Funding Amount
$554,656.00
Summary
Cells in some regions of the brain, collectively known as the sensorimotor cortex, control our capacity to purposefully move the arms and hands. Damage to these regions in adults causes severe deficits. However, rehabilitative training can restore some control over the muscles. To understand how the brain circuits change to compensate for injury, and what effect rehabilitation may have on these changes, I will study cellular alterations in the movement control pathways in the cerebral cortex.
The Diagnosis Of Depression In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$361,000.00
Summary
During the next 3 decades the number of persons older than 85 years will more than double, and the health care need of this burgeoning population are assuming greater importance. Among the most significant but often overlooked conditions in the elderly is depression, which is associated with marked disability, functional decline, risk of hospitalization, diminished quality of life, caregiver burden, increased service utilization, and mortality from comorbid medical conditions or suicide. The Wor ....During the next 3 decades the number of persons older than 85 years will more than double, and the health care need of this burgeoning population are assuming greater importance. Among the most significant but often overlooked conditions in the elderly is depression, which is associated with marked disability, functional decline, risk of hospitalization, diminished quality of life, caregiver burden, increased service utilization, and mortality from comorbid medical conditions or suicide. The World Health Organization predicts that by 2020 depression will be second only to heart disease as a cause of disability and premature death in established market economies. Depression is missed in approximately half of all elderly persons with mood disorder, and this frequency is certainly higher among individuals with dementia. The strategy to diagnose depression in dementia needs to be revised. Patients' reports are often unreliable due to memory problems and lack of full insight into their mood and behavioural changes. Caregivers may overestimate patients' symptoms of depression, especially when they themselves are depressed and overburdened, and clinicians' diagnoses are sometimes based on biased information and short observation periods. The situation in nursing homes is even worse, and there is a shortage of studies on how to diagnose depression in institutionalised patients with dementia. Using specific instruments to assess mood, behaviour and cognition we will develop valid and reliable criteria to diagnose depression in the different stages of dementia, and for patients living in different settings. This will facilitate the early recognition and adequate treatment of depression in individuals with dementia, it will greatly improve patient's quality of life, and will have a positive impact on caregivers' psychological well-being.Read moreRead less