Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently require ....Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently required. The sequencing of the human genome and advanced screening technology (microarrays) allow the detailed analysis of expression patterns in large numbers of specimens. We propose to study the genetic features of this disease by investigating 28 childhood ALL patients from whom we have stored specimens received at two time points, one at diagnosis and one at relapse. The hypothesis of this study is that relapsed leukaemias display genetic features which are correlated to their resistance to therapy. The specific questions we will be asking are: (1) Which genes are expressed at high levels in leukaemia specimens at the time of relapse while not expressed (or expressed at lower levels) at the time of diagnosis and vice versa? (2) What is the function of differentially expressed genes? (3) Is the pattern of gene expression correlated with resistance to the particular drug therapy used? (4) Is the leukaemia clone at relapse related or unrelated to the clone present at diagnosis, as determined by receptor rearrangement? The expression levels of identified discriminator genes will be confirmed by real-time quantitative polymerase chain reaction (PCR). The quality of this set of specimens makes them particularly suited to achieve the stated goals, providing a unique opportunity to investigate drug resistance in childhood ALL. The data generated will provide the basis for the examination of genes suitable as new therapeutic targets.Read moreRead less
Life Threatening Cancer Across The Lifespan: Examining The Relevance Of Music To Patients And Their Companions
Funder
National Health and Medical Research Council
Funding Amount
$137,000.00
Summary
Although music is widely used, scant discussion about its therapeutic merit exists when compared to the spoken word. Throughout the Ages, ritualized music promoted health and loss adjustment, however, music is not pivotal in modern medicine. The research will examine people’s intuitive music usage when experiencing life threatening cancer and the relationship between music therapy participation and one’s later music experience. Findings will inform specific recommendations for music therapists a ....Although music is widely used, scant discussion about its therapeutic merit exists when compared to the spoken word. Throughout the Ages, ritualized music promoted health and loss adjustment, however, music is not pivotal in modern medicine. The research will examine people’s intuitive music usage when experiencing life threatening cancer and the relationship between music therapy participation and one’s later music experience. Findings will inform specific recommendations for music therapists and generic guidelines to extend music’s therapeutic effect in palliative care.Read moreRead less
Protein Topogenesis And The Assembly/disassembly Of The Enveloped Hepatitis B Virus.
Funder
National Health and Medical Research Council
Funding Amount
$197,884.00
Summary
An estimated 350 million people worldwide, and 250,000 in Australia, are chronically infected with the hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current treatments are inadequate. A major obstacle to the study of this virus is the lack of a cell culture infection system. We have used the duck hepatitis B virus (DHBV) model to study the events leading up to assembly of the virus in ....An estimated 350 million people worldwide, and 250,000 in Australia, are chronically infected with the hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current treatments are inadequate. A major obstacle to the study of this virus is the lack of a cell culture infection system. We have used the duck hepatitis B virus (DHBV) model to study the events leading up to assembly of the virus in a way which prepares the viral envelope or outer coat for its foray into a new host cell. The project will examine the specific interactions of two proteins, the large and the small envelope protein, in addition to a third envelope protein we have recently discovered, which together make up the viral envelope. This will reveal which envelope components are required to make up the specific structures known to be essential for the disruption of the host cell membrane and subsequent entry of the virus to a new cell. An understanding of the changes that occur to the viral envelope upon entry will enable development of strategies for the inhibition or blocking of this change, thus identifying targets for the development of new antiviral agents. Because HBV is just one of many viruses which have an envelope, all of which must enter the cell in some way, our studies of HBV will also provide new clues with respect to the replication of other viruses such as measles, influenza and HIV. A related part of the study will examine the orientation of the large envelope protein within the virus particle and how it changes its orientation to assume its many important functional roles, in the late stages of particle assembly. Expanding on our finding that the small protein is essential to the orientation of the large protein, this study will reveal the mechanism of a unique method of protein transport which may have wider implications in cell biology.Read moreRead less
The Role Of IQGAP1 In Human High-Grade Glioma And Its Regulation By MiR-124-A
Funder
National Health and Medical Research Council
Funding Amount
$69,137.00
Summary
Survival rates for many cancers are improving, however, for most patients diagnosed with a high grade glioma (HGG) there is limited long term survival. The treatments administered have limited effectiveness due to extensive infiltration of the tumour cells. New therapeutic strategies targeting the invading cell population to further reduce tumour spread are needed. Hence, a better understanding of the mechanisms promoting glioma migration and invasion are urgently required in this fatal disease.
I am a vascular surgeon. My research is centred on the following problems relevant to my patients: 1. The management of aortic aneurysm. 2. The management of occlusive atheroma, particularly unstable atheroma, aortic calcification, intermittent claudicati
Polynucleotide Vaccine Based On Targeted Delivery To Antigen Presenting Cells
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
We have previously generated a vaccine for breast and other adenocarcinomas by linking a breast cancer associated protein, MUC-1, to a sugar called mannan. This complex was capable of eradicating tumours in mice and its efficacy has been evaluated in human clinical trials (12 in total). As an extension to these studies we have now found that this sugar, mannan, can be used to deliver DNA to immune cells. The current project will evaluate a DNA vaccine for breast cancer.
Conditionally Replicative Adenoviruses For Mesothelioma Therapy
Funder
National Health and Medical Research Council
Funding Amount
$260,600.00
Summary
Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy ....Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy relies on selective viral replication in (and therefore death of) tumour cells but not normal cells. In principle, mesothelioma is an attractive target for this therapeutic approach owing to its propensity to remain localised to the pleural space until late in the disease. However, for any CRAd strategy to succeed, viral replication must be limited to the tumour cells so as not to cause unnecessary toxicity to normal tissues. This level of specificity can potentially be achieved by using cell-specific promoters to control the expression of viral genes essential for replication. To date however, there have been no reports evaluating candidate mesothelioma-specific promoters in adenoviral vectors. Furthermore, other issues such as tumour a lack of viral receptors or tumour-associated fibrosis could limit viral spread through a mesothelioma mass and reduce the efficacy of the approach. In this proposal we will contruct and test CRAds which are controlled by promoters which we believe will be highly active in mesothelioma, but very poorly active in other tissues. We will test the ability of these new agents to kill mesothelioma cells in tissue culture, in pieces of mesothelioma tumours removed from patients, and in animal models. If successful, this approach could offer new hope for mesothelioma patients.Read moreRead less