Molecular Characterisation And Diagnosis Of Malignant Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$421,250.00
Summary
Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in ....Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in cases of mesothelioma is not expected until 2010. MM is one of the most aggressive and debilitating tumours known, with a median survival of 7-10 months and a clinical pattern that usually involves substantial pain and dyspnea. Advances in therapy-prevention of mesothelioma will have not only have a major health impact, but potentially an extraordinary economic impact. MM is predicted to cost the Australian economy around $5 billion in compensation over the next 35-40 years. Government, insurance companies and industry will share that cost. The significance of this disease therefore extends beyond its actual incidence. There is growing evidence in many tumour types that the best diagnostics and treatments for cancer will come about as a result of understanding the molecular logic that underpins carcinogenesis, and designing therapies and diagnostics accordingly. We will carry out a project using the most comprehensive microarrays available to profile gene expression in malignant mesothelioma. We will use the expression data we obtain to fulfil three aims. Firstly, we will use patient outcome information to search for genes whose expression is indicative of response to therapy. Secondly, we will search the data to identify candidate secreted molecules which may be useful in the early detection of MM. Finally, we will develop a molecular assay to unequivocally diagnose MM from cells collected from pleural effusions.Read moreRead less
Defining Steps In The Molecular Pathogenesis Of Lung Cancer Using Immortalized Human Bronchial Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$374,344.00
Summary
Lung cancer remains the leading cause of cancer death worldwide and is caused by abnormalities in DNA. This project aims to further our understanding of this disease by altering known cancer-related genes and studying their effect on lung cancer development. This project also aims to identify novel genes in lung cancer as well as tumour expression profiles which can predict response to chemotherapy agents. In summary, this research will identify new gene targets for therapeutic agents.
Molecular Classification Of Carcinoma Of Unknown Primary
Funder
National Health and Medical Research Council
Funding Amount
$418,250.00
Summary
Carcinoma of unknown primary (CUP) is the fourth largest cause of cancer death. The condition has a particularly poor outlook, with a median survival of less than one year. Current methods for diagnosis of CUP include histopathology and sophisticated imaging. These are successful in approximately 40% of cases. Frequently the reason for the poor outcome in this disease is that the 60% of patients with CUP for whom no diagnosis is made do not benefit from chemotherapy specifically designed for a p ....Carcinoma of unknown primary (CUP) is the fourth largest cause of cancer death. The condition has a particularly poor outlook, with a median survival of less than one year. Current methods for diagnosis of CUP include histopathology and sophisticated imaging. These are successful in approximately 40% of cases. Frequently the reason for the poor outcome in this disease is that the 60% of patients with CUP for whom no diagnosis is made do not benefit from chemotherapy specifically designed for a particular tumour origin. These patients receive a less effective, generic, chemotherapy. The aim of this project is to use microarrays to identify the gene expression profile in many known tumours to create a molecular fingerprint of the various tumour types. By comparing the fingerprint from a CUP with the database we should be able to identify the true tumour type in CUP, and allow patients to benefit from more specific chemotherapy.Read moreRead less
Molecular Profiling Of Sarcomas To Enable Clinical Prediction And Elucidate Molecular Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
Sarcomas are uncommon cancers which affect the young, with a 50% mortality. Treatment involves an expert multidisciplinary approach, and even when effective often entails long-term loss of quality of life. Most sarcomas are treated with a combination of radiotherapy and surgery, which improves survival significantly compared to surgery alone. Radiotherapy does not help all patients, has side-effects and is expensive and time consuming. It would be useful to be able to identify patients who will ....Sarcomas are uncommon cancers which affect the young, with a 50% mortality. Treatment involves an expert multidisciplinary approach, and even when effective often entails long-term loss of quality of life. Most sarcomas are treated with a combination of radiotherapy and surgery, which improves survival significantly compared to surgery alone. Radiotherapy does not help all patients, has side-effects and is expensive and time consuming. It would be useful to be able to identify patients who will not benefit from radiotherapy, to minimise unnecessary harm from treatment and offer alternate more effective therapies. Unfortunately, we cannot yet distinguish which tumours will respond and which will not. Moreover, the uderlying causes of sarcoma are poorly understood. This project has two aims: first to make our current therapies more effective by targeting those who will not benefit from standard treatment; and second to better understand the causes of sarcoma, in order to develop better treatment. Microarrays enable the simultaneous study of thousands of genes, which when combined form a unique portrait of each tumour. Our unit, one of the largest sarcoma sevices in Australia, has access to large numbers of tumour samples, with excellent basic science support. It is now possible to ask what the molecular 'portrait' is of sarcomas which are responsive to radiotherapy, using tiny amounts of tumour material which can be obtained before treatment starts. We also hope to identify the molecular basis of sarcomas by finding the key genes whose inactivation is central to the development of this form of cancer. Such genes can then form the basis of targeted therapy. This approach will lay a solid foundation for future research into sarcomas, and has the potential to reduce unnecessary cost and suffering patients experience from treatments which are unlikely to be effective.Read moreRead less
Investigating A Novel Genetic Regulator Of Cardiac Rhythm
Funder
National Health and Medical Research Council
Funding Amount
$557,101.00
Summary
Cardiac arrhythmias affect approximately 5% of the population and have a high association with sudden death. Whilst the cause of cardiac arrhythmia is complex, we know that genetic mutations play a role however we don't know all the genes important for cardiac rhythm. It is imperative that we identify all the genes in this process, so we can determine which mutations cause arrhythmia. We have identified a new gene that causes cardiac arrhythmia and seek to understand how it functions.
Systemic lupus erythematosus (SLE) is a condition which causes inflammation in many different organs and can lead to significant suffering and death. Glucocorticoids (GC) are very good at controlling inflammation, however they have severe side effects such as diabetes and bone thinning, and cannot be used long term. This project aims to investigate a protein “GILZ” in patients with SLE. GILZ may have similar anti-inflammatory effects to GC but may not be associated with the same side effects.
Waxing And Waning Of Asthma During Transition From The Teens To Adulthood: Identification Of Immunophenotypic Markers To Predict Disease Trajectory And Guide Development Of Treatment Strategies To Prevent Progression To Chronicity
Funder
National Health and Medical Research Council
Funding Amount
$736,166.00
Summary
The project will seek to identify biomarkers in teenage/young adult asthmatics that can distinguish between those who are "growing out" of the disease, versus those who are progressing towards chronic severe asthma. This knowledge will inform the development of more effective treatment programs for this age group.
Computational Reconstruction And Validation Of A Gene Regulatory Network Controlling Differentiation Of B Cells To Antibody-secreting Plasma Cells
Funder
National Health and Medical Research Council
Funding Amount
$618,152.00
Summary
Regulation of B cell differentiation, which occurs when our body responds to antigen infection is tightly controlled by a gene regulatory network. This project will be the first study to reconstruct a regulatory network for this process by using genome-wide expression and transcription factor binding data. The research finding from this study will elucidate the molecular mechanisms regulating this process and will shed new light on how this network is altered in lymphoma and myeloma.