A National Resource For Mouse Models Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$483,643.00
Summary
Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resour ....Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resource to maintain and distribute these cell lines. In addition, we describe a new transgenic mouse model in which mesotheliomas are rapidly induced in the peritoneal cavity after exposure to asbestos, recreating the natural tumour development much more accurately. These mice have been engineered to express the cancer causing protein of a monkey virus (SV40 large T antigen) in their mesothelial cells because it has been suggested that the virus has a role in the development of mesothelioma. This application also seeks funding to use the MexTAg mice to test the usefulness of different therapies for the prevention or treatment of mesothelioma. These animals give us the ability to investigate the disease in a more realistic environment than previous models. In parallel collaborative studies with other groups investigating different aspects of the biology of this cancer, we plan to analyze the earliest changes in the development of the disease and search for early markers using proteomics and gene expression studies. We anticipate that this model will generate information more directly relevant to understanding the human disease and will provide essential experimental data for clinical trials.Read moreRead less
Transforming Growth Factor Beta Signalling In Malignant Mesothelioma Growth And Collagen Production
Funder
National Health and Medical Research Council
Funding Amount
$509,917.00
Summary
Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced M ....Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced MM growth. How cancer cells regulate ECM production and control their growth is unclear but strong evidence suggests the growth factor transforming growth factor-beta (TGFB) plays an important role. We and others showed that MM cells secrete all forms (1-3) of TGFB, and TGFB1,2-like activity has been reported in pleural effusions from MM (4,5). All TGFB forms stimulate MM cells to grow and make ECM (6,7). We showed that high levels of collagen produced by MM are enhanced by TGFB. Small molecules called antisense oligonucleotides (AO) which blocked production of TGFB2 by cells, reduced MM cell growth in soft agar, a characteristic of cancer, and partially blocked MM growth in animal models (4,6). This was supported by studies using soluble TGFB type II receptors, which blocks TGFB1,3 (8), and our studies using TGFB2 specific antibodies, as both studies reduced tumour growth. These findings support a role for TGFB in MM growth. However, all TGFB forms can promote cell grow and collagen synthesis and therefore ways to block all TGFB forms are required to ensure maximal effect. This study will examine the effect of blocking common downstream signalling pathways of all three TGFB isoforms on MM collagen production and tumour growth. These pathways are activated when TGFB binds to its receptors sending messages to the nucleus of the cell to make collagen or grow. By identifying which TGFB signalling pathway is important, we may be able to design novel therapeutic approaches to help treat patients with this disease.Read moreRead less
Body Composition Changes In Cardiac Cachexia: Pathophysiology, Quantification And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$120,000.00
Summary
Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an exam ....Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an examination of the effects of exercise on measures of cachexia in patients with congestive heart failure. The researchers believe that this study will supply valuable new information about the development of cachexia and lead to new therapies for this syndrome.Read moreRead less
Gene Based Treatment Strategies For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$2,630,000.00
Summary
Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project ....Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project aims to develop a potentially permanent solution to alleviate diabetes-related blindness in the world. The project combines several very recent scientific advances into one strategy to combat diabetic retinopathy at a molecular level. Vision is our most important sensory organ that cannot be replaced. Thus, human trials can only be conducted following extensive animal safety and efficacy trials. To date the development of new therapies has been seriously hampered by the lack of appropriate, easy to reproduce animal models for different stages of diabetic retinopathy. In addition, it aims to identify new therapeutic agents from molecules that are naturally produced by the retina while fighting the disease. Finally, tested and evaluated in the animal models. The most successful therapeutic candidates will then be further developed for human trials.If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
Remote Indigenous Oral Health Testing A Commmunity Based Model Of Oral Health Promotion
Funder
National Health and Medical Research Council
Funding Amount
$77,152.00
Summary
Development and trial of an oral health promotion package for remote Aboriginal groups based on community consultations. This would include the development of visual health promotion packages in local language. The aim is to develop sustainable change in oral health behaviours.
Determining Critical Points In The Potential Palliative Care Pathway In The Last Year Of Life
Funder
National Health and Medical Research Council
Funding Amount
$356,461.00
Summary
People with serious illnesses who are approaching the end of their lives undergo a journey where, along the way, they experience several critical points. Although we know these critical points are crucial to how they might access the best kind of care, we are unsure exactly when these points may occur and how they may vary for different kinds of people. We need to know when is the best time to start withdrawing invasive and purely curative treatments, when are discussions about approaching death ....People with serious illnesses who are approaching the end of their lives undergo a journey where, along the way, they experience several critical points. Although we know these critical points are crucial to how they might access the best kind of care, we are unsure exactly when these points may occur and how they may vary for different kinds of people. We need to know when is the best time to start withdrawing invasive and purely curative treatments, when are discussions about approaching death best introduced and how we can care for people from a diverse range of backgrounds and beliefs within our current health care system. We also need to identify and promote the best possible ways of supporting patients at the end of life and their families as they negotiate the often complex path towards a good death. With this kind of information, health care practitioners, particularly those involved in palliative care, can design better services that put in place pathways where assessment of patient and family needs, referral to the most appropriate services and coordination of all the aspects of care are easy to understand and access for all people. This kind of care can be expensive so we need to use the money allocated to palliative care wisely. This can be achieved with thoughtful research that identifies those most in need, at the time of most need and investigates the best approaches to alleviating pain in suffering in the weeks and months before death. A fair and equitable health care system is not just about keeping people healthy, but also about dealing humanely with the inevitability of deathRead moreRead less
Development And Implementation Of An Educational Program To Guide Palliative Care For People With Motor Neurone Disease
Funder
National Health and Medical Research Council
Funding Amount
$258,525.00
Summary
The project aims to improve the quality of care for people with MND and their family carers through the development, testing and implementation of an educational program for health professionals and other service providers focused on the palliative care needs of this population. The project is taking place in three sites: Western Australia, Victoria and South Australia, in collaboration with the MND associations in the three states. The effectiveness of the flexible model of care provided to peo ....The project aims to improve the quality of care for people with MND and their family carers through the development, testing and implementation of an educational program for health professionals and other service providers focused on the palliative care needs of this population. The project is taking place in three sites: Western Australia, Victoria and South Australia, in collaboration with the MND associations in the three states. The effectiveness of the flexible model of care provided to people with MND and their carers as a result of the implementation of the MND Education Program will be assessed and a national implementation plan will be developed.Read moreRead less
1+1- A Healthy Start To Life:Targeting The Year Before And The Year After Birth In Aboriginal Children In Remote Areas
Funder
National Health and Medical Research Council
Funding Amount
$587,272.00
Summary
Indigenous Australians in remote communities are less healthy and more socially disadvantaged than other Australians. This influences the quality of the intrauterine environment. Babies often suffer malnutrition and recurring infections during infancy which are exacerbated by their less than optimal birth status and contribute to chronic conditions (diabetes, cardiovascular disease, renal failure) in adulthood. Existing health services are costly to Government and do not achieve their potential ....Indigenous Australians in remote communities are less healthy and more socially disadvantaged than other Australians. This influences the quality of the intrauterine environment. Babies often suffer malnutrition and recurring infections during infancy which are exacerbated by their less than optimal birth status and contribute to chronic conditions (diabetes, cardiovascular disease, renal failure) in adulthood. Existing health services are costly to Government and do not achieve their potential for promoting health and providing quality care. Evidence suggests redesigned models based on continuity of care, focused, proactive family support and workload reform will improve maternal and infant outcomes. New models need to be developed, costed, implemented and evaluated providing governments with the evidence base to initiate service improvement. Such models will have applicability elsewhere in Australia. Professor Lesley Barclay and her team of researchers from Charles Darwin University will conduct research into developing such a model. The project aims to improve the quality of care for remote dwelling Aboriginal women and infants in the year before, during and the year after birth by providing evidence for, and facilitating changes to, service delivery. This will enhance the potential for the development of resilience and well-being of their children. It will also test if service improvements can improve the health of women and reduce childhood disease and therefore reduce the impact of health conditions occurring in adulthood which have their origins in the early stages of life.Read moreRead less