LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.Read moreRead less
Supply, Demand And The Distribution Of Health Services In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,038.00
Summary
The distribution of medical services and its impact on access and equity is widely recognised as a key concern of the Australian community. Access and equity are key indicators to the public of the performance of a health system. These concerns have led to the adoption of major policy goals under Medicare relating to equitable access to medical services for the population as a whole. Furthermore, both the community and policy makers have expressed high levels of concern over the distribution of ....The distribution of medical services and its impact on access and equity is widely recognised as a key concern of the Australian community. Access and equity are key indicators to the public of the performance of a health system. These concerns have led to the adoption of major policy goals under Medicare relating to equitable access to medical services for the population as a whole. Furthermore, both the community and policy makers have expressed high levels of concern over the distribution of medical services between sub-markets and sub-populations, in particular, in the distribution of medical services between urban and rural-remote areas. This project, for the first time, comprehensively examines the performance of Medicare in terms of access to medical services over time. Australian data sets, largely untapped by economic modelling, will be used for analysis of the relationships between the distribution of, access to, and demand and fees for Australian medical services and their impact upon mortality over time. The study will result in the first comprehensive Australian description of access and supply of different medical services by social group and by geographic location over time. Furthermore it will provide evidence on the key determinants of distribution and changes in the distribution of medical services and estimates the likely effects of policy instruments designed to address the distribution of, and access to, medical services.Read moreRead less
A Randomised Control Trial Of Non-specific Clinical Management Versus CBT In Chronic Anorexia Nervosa
Funder
National Health and Medical Research Council
Funding Amount
$555,843.00
Summary
Anorexia nervosa (AN) is a serious mental illness that usually starts in adolescence and often runs a chronic course. With an estimated prevalence rate between 0.5% and 3.7% of women, and up to 50% remaining chronically ill, the illness poses a disproportionate burden on health and social services. AN has inpatient costs alone that exceed that for schizophrenia. Chronic AN has the highest mortality rate of any mental illness. Chronic AN patients are known for their ambivalence about engaging in ....Anorexia nervosa (AN) is a serious mental illness that usually starts in adolescence and often runs a chronic course. With an estimated prevalence rate between 0.5% and 3.7% of women, and up to 50% remaining chronically ill, the illness poses a disproportionate burden on health and social services. AN has inpatient costs alone that exceed that for schizophrenia. Chronic AN has the highest mortality rate of any mental illness. Chronic AN patients are known for their ambivalence about engaging in treatment and poor motivation to change their eating disorder behaviours. They often fail to respond to traditional treatments and develop a history of negative treatment experiences and repeated treatment failures. A new approach is needed to reduce both the personal suffering and the burden of the illness on social and medical services. To date, there has been little scientific investigation into the development of specific treatment for those patients with chronic AN. This study will trial a recently manualised therapy - non-specific supportive clinical management - which initial evidence suggests may hold promise for chronic AN because it offers a more indirect, motivationally-matched approach. This treatment will be compared to the establishment therapy Cognitive Behavioural Therapy. Patients will be randomly allocated to one of the two treatment conditions and will receive 40 sessions over 12 months. They will be thoroughly assessed prior to during and after they have completed treatment and followed up for 6 months. This is the worlds first trial of a psychological treatment for chronic AN; it is hoped the study will establish an effective treatment for this debilitating and expensive illness. Further, as the project aims to explore the core, but often over-looked, feature of AN - poor motivation for recovery - it will also be in a position to shed light on the deep psychological processes that maintain this illness.Read moreRead less
Measuring The Productive Efficiency Of Hospitals - A Comparison Of Parametric And Non-parametric Approaches
Funder
National Health and Medical Research Council
Funding Amount
$61,815.00
Summary
In the face of rising health service costs, an ageing population, and falling private health insurance rates, the efficient use of scarce health service resources has become a central theme in health system reform. Productive (or technical) efficiency is a key aspect of health system reform - that given health services are produced with the minimum feasible amount of resources. Despite the importance of technical efficiency there have been few published studies in Australia which measure technic ....In the face of rising health service costs, an ageing population, and falling private health insurance rates, the efficient use of scarce health service resources has become a central theme in health system reform. Productive (or technical) efficiency is a key aspect of health system reform - that given health services are produced with the minimum feasible amount of resources. Despite the importance of technical efficiency there have been few published studies in Australia which measure technical efficiency in the health sector. This study will develop theoretical and empirical approaches to measuring technical efficiency in the production of hospital services using data from Victoria. Measures of hospital technical efficiency will be developed using two quantitative modelling approaches: stochastic frontier modelling and data envelopment analysis. Results will be used to investigate the impact of patient and hospital characteristics on efficiency, and to identify economies of scale and scope in the provision of hospital services. The robustness of results to changes in variables, the sample of hospitals studied, and model assumptions will be tested, and two techniques will be compared to assess their appropriateness in the health services context which has not previously been done. Criteria for assessing the approaches include the degree to which: assumptions affect the robustness of results; the techniques capture the salient features of health services production; and the techniques produce similar rankings and estimates of inefficiency. The methods used will represent a significant contribution to international knowledge of hospital efficiency measurement, and the relationships between hospital characteristics, casemix, and efficiency. The study wil provide improved measures of hospital efficiency in Victoria, and will inform debate on hospital funding policy.Read moreRead less
A Genome-wide Search For Genes Underlying The Developmental Origins Of Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,022,552.00
Summary
Epidemic rises in the incidence of many chronic diseases such as obesity, type 2 diabetes, hypertension, coronary artery disease and mental illness have occurred in Australia over the last two decades. Antenatal, early life and childhood factors have been consistently associated with the development of such diseases. We propose to conduct a genome-wide scan in an exceptional longitudinal birth cohort in order to identify the genetic mechanisms linking early life event and adult disease.
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less
Clinical Impact Of Clonal Pseudomonas Aeruginosa In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$547,238.00
Summary
In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on ....In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on the major bacterial problem, Pseudomonas aeruginosa. Several studies from Australia and the UK, including our own have shown that about 30% to 45% of patients share the same strain of Pseudomonas aeruginosa within a centre. We know that two dominant strains of Pseudomonas aeruginosa are found in CF centres on the eastern board of Australia. This is unexpected as this bacterium is usually acquired from the environment. The emergence of these clonal strains is causing increasing anxiety in the CF community. This study is designed to provide vitally needed information on the clinical implications of being infected by an clonal strain of Pseudomonas aeruginosa and the risk factors for the acquisition of an clonal strain. This new information will provide a rationale basis for the need for changes to infection control policies (including patient segregation), better outcome predictors for patients infected with clonal strain of Pseudomonas aeruginosa.Read moreRead less
The Role Of Arousal And Respiratory Control Factors In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$567,924.00
Summary
Sleep apnoea (OSA) is a very common breathing disorder in sleep characterized by repetitive closure of the collapsible portion of the throat with serious effects on sleep quality and health. Basic causes of OSA are still largely unknown. We will investigate waking responses to breathing load and related respiratory control factors that we believe may be fundamental causes of OSA, and potentially explain many features of OSA including worsening in light sleep and with increasing age.
A Trial Of A Multidisciplinary, Group Based Intervention To Meet The Needs Of Men With Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$524,285.00
Summary
This study will test an innovative approach to meeting the physical and psychosocial needs of men with early stage prostate cancer using a randomised controlled trial. This novel approach involves a combination of individual and group-based consultations which encourages peer-to-peer support, promotes self-care and enhances appropriate multidisciplinary referrals and communication. It provides a new model of care for patients with chronic diseases that can be translated into clinical practice.
Tracking The Impact Of Drug Regulatory Actions: Consumer Health Outcomes, Risk-benefit Issues And Policy Framework.
Funder
National Health and Medical Research Council
Funding Amount
$439,324.00
Summary
This study will explore what happens in the community when a medicine is withdrawn from the market or discredited due to safety concerns. It will examine the impacts of two recent cases of medicine withdrawal or serious long-term safety concern, on a large cohort of women with high utilisation rates who were monitored during the time the medicines were discredited. The study will be an important guide to future regulatory, media and provider responses when medicines are discredited.