A Randomised Phase III Study Of Radiation Doses And Fractionation Schedules In Non-low Risk DCIS Of The Breast
Funder
National Health and Medical Research Council
Funding Amount
$1,751,209.00
Summary
Treatment of ductal carcinoma in-situ (DCIS), a preinvasive form of breast cancer, is aimed at preventing invasive cancer recurrence. Women with higher-risk DCIS have an increased risk of recurrence. This study aims to individualise treatment for women with DCIS to achieve long-term tumour control with minimal treatment toxicity. After local excision of DCIS, radiotherapy (RT) to the whole breast reduces the recurrence rate. However, it is unclear if escalating radiation dose to the tumour bed i ....Treatment of ductal carcinoma in-situ (DCIS), a preinvasive form of breast cancer, is aimed at preventing invasive cancer recurrence. Women with higher-risk DCIS have an increased risk of recurrence. This study aims to individualise treatment for women with DCIS to achieve long-term tumour control with minimal treatment toxicity. After local excision of DCIS, radiotherapy (RT) to the whole breast reduces the recurrence rate. However, it is unclear if escalating radiation dose to the tumour bed in higher-risk women increases tumour control. It is also uncertain if giving fewer but larger radiation doses over 3-4 weeks would achieve the same tumour control as the standard 5-7 week course of RT to improve patient convenience and access to RT. Thus, this multicentre study of 610 women with higher-risk DCIS will investigate if adding a tumour bed radiation boost after whole breast RT improves tumour control, and the shorter RT course achieves the same tumour control as the standard longer course. Currently, the ability to predict the malignant potential of DCIS and RT toxicity is limited. This study will investigate if there are biological and genetic markers predictive of invasive recurrence and normal tissue toxicity in women with DCIS using state of the art technology. Women need to weigh up the likelihood of cancer control against adverse treatment effects to make an informed treatment decision. However, very little is known about the quality of life (QoL) consequences of the diagnosis and treatment of DCIS. In this study, the QoL, psychological distress, perceived risk of invasive cancer recurrence and perceived cosmetic outcomes of women with DCIS, will be assessed using a questionnaire of validated measures. This study will refine treatment for women with DCIS according to their risks of recurrence. It will significantly advance the understanding of the biology of DCIS and its psychological and QoL outcomes after treatment.Read moreRead less
We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other co ....We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other countries (in North and South America, Asia, and Europe). This study will provide the first nationally-representative information on the burden of chronic obstructive pulmonary disease (COPD) and the opportunities for health gain by improving the management of this illness. In Australia, COPD is a relatively silent and under-recognised disease but nevertheless is the third most important contributor to the burden of disease and the third leading cause of hospital admission as well as being the underlying cause of 4.2% of all deaths. The information we will collect is needed to form a basis for prevention and disease management interventions to reduce the burden of COPD, particularly among population sub-groups who are disproportionately affected, either due to greater exposure to risk factors (mainly tobacco smoking and occupation), greater susceptibility, under-recognition and under-diagnosis, or inadequate disease management. Importantly, the study will serve to raise awareness about the hazards of smoking for all Australians. By identifying target groups, prevalent exposures and management deficiencies, it will lead the way towards policy-relevant randomised controlled trials testing community-based interventions to prevent COPD and-or manage it more effectively. The information collected will help advance knowledge of the prevalence, burden and treatment of COPD that will be relevant to communities throughout the world.Read moreRead less
An Examination Of Motor Functioning In Autism And Asperger's Disorder: An Analysis Of Gait & Cortical Brain Activity.
Funder
National Health and Medical Research Council
Funding Amount
$120,220.00
Summary
Autism is a developmental disorder characterised by a triad of deficits: delayed and atypical language development, impaired development of social skills, and ritualistic and stereotypic behaviour. Although not part of the standard diagnosis, movement disorders and gait abnormalities have been clinically observed in autism similar to those seen in Parkinson's disease. In addition, individuals with Asperger's disorder may appear more clumsy, have a stiff or awkward way of walking, and exhibit poo ....Autism is a developmental disorder characterised by a triad of deficits: delayed and atypical language development, impaired development of social skills, and ritualistic and stereotypic behaviour. Although not part of the standard diagnosis, movement disorders and gait abnormalities have been clinically observed in autism similar to those seen in Parkinson's disease. In addition, individuals with Asperger's disorder may appear more clumsy, have a stiff or awkward way of walking, and exhibit poor coordination in posture and gesture. It has been suggested that there is disruption within the basal-ganglia-thalamocortical circuitry (the region connecting the frontal and sub-cortical structures), which may cause the motor dysfunction seen in autism and Asperger's disorder. Few studies have attempted to isolate particular stages of motor functioning which may account for the coordination and motor delay observed clinically in autism and Asperger's disorder. A recent study of ours found evidence to suggest that motor planning deficiencies may account for the 'clumsy' movement patterns frequently reported in the autism - Asperger's disorder literature. Therefore, the aim of this research is to provide a comprehensive neurobehavioural and neurophysiological analysis of motor functioning in young people with autism and Asperger's disorder to further examine the exact stages of motor processing which are deficient in these disorder groups. Recent retrospective studies have shown that even as infants children with autism exhibit clear features of motor disturbance, which, if detected and clearly defined, could advance early diagnosis. In addition to advancing the clinical definition of autism and Asperger's disorder, a careful examination of motor disturbance may also illuminate the neurobiological underpinnings of these disorders.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Epimutations As Germ-line Defects In Hereditary Cancer Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$385,925.00
Summary
Traditionally familial cancers were thought to be caused and inherited by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that a 'chemical coat' around the MLH1 gene, causing it to be switched off, can also be inherited in some cases of bowel cancer, without any mistakes within the gene's code. We will determine if this 'coat' causes other types of cancer and if this runs in families. We also hope to find out how the coat is formed and may be reversed.
How Do Thick Airway Walls Affect Airway Hyperresponsiveness In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Asthmatic airways narrow too easily, a characteristic called airway hyperresponsiveness (AHR). To understand the cause of asthma we need to understand the cause of AHR. Thickened airway walls could amplify airway narrowing and increase AHR. However, thick airway walls are also stiff, and stiff walls could reduce narrowing and AHR. This project will examine the relationships between AHR and airway wall thickness and stiffness during and after treatment that reduces airway wall thickness.
Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less
Randomised Controlled Trial Of Virtual Reality Therapy After Stroke
Funder
National Health and Medical Research Council
Funding Amount
$452,264.00
Summary
Stroke is the second largest cause of disability in Australia. There is no cure, so patients must rely on therapy to restore movement. We want to make rehabilitation more effective. This study compares virtual reality game therapy (using the Nintendo Wii) to current best practice (constraint therapy). We anticipate patients will improve more with Wii therapy. Because it is fun, patients will enjoy therapy and spend longer training resulting in a greater recovery and better movement ability.
The Role Of Snoring Vibrations In The Pathogenesis Of Early Carotid Artery Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$593,833.00
Summary
Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that snoring may be an independent risk factor for the development of stroke. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which may damage the artery wall and subsequently lead to stroke. This may lead to new strategies to treat habitual snoring.
MICROFABRICATED DEVICES: A SIGNIFICANT ADVANCE FOR THE DETECTION AND MOLECULAR ANALYSES OF CIRCULATING CANCER CELLS?
Funder
National Health and Medical Research Council
Funding Amount
$422,107.00
Summary
Using advanced microfabrication concepts, this project aims to develop a platform technology able to capture tumour cells circulating in the blood of cancer patients. Although present only in extremely small numbers, these cells provide invaluable insights into the pathophysiology of the disease and consequently provide vital diagnostic and prognostic information. Molecular analyses of these cancer cells could ultimately enable the design of improved and personalized cancer treatment.