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Gene Expression Changes Induced Upon Beta3 Integrin Expression In Human Melanoma Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$199,413.00
Summary
Diagnostic and prognostic markers for metastatic melanoma are essential to better understand the development of this cancer. One of the most effective markers so far found to correlate with invasiveness of tumour cells, and hence lethality of melanoma, is the Beta3 integrin molecule. When this protein is expressed on the surface of early stage melanoma cells, that in themselves are not able to form metastatic tumours, they convey upon the cells the ability to proceed from growing on the surface ....Diagnostic and prognostic markers for metastatic melanoma are essential to better understand the development of this cancer. One of the most effective markers so far found to correlate with invasiveness of tumour cells, and hence lethality of melanoma, is the Beta3 integrin molecule. When this protein is expressed on the surface of early stage melanoma cells, that in themselves are not able to form metastatic tumours, they convey upon the cells the ability to proceed from growing on the surface of the skin (radial growth phase) to allowing them to invade the skin (vertical growth phase). It is not clear how expression of Beta 3 allows this change in growth state to occur and this research program is designed to test if Beta 3 is the direct cause of gene expression changes mediating the metastatic transformation. To provide insight into the genetic changes induced in melanoma cells expressing the Beta3 protein a screen for genes that are either activated or repressed in the presence of Beta3 will be performed. Non-metastatic melanoma cells will be transduced with the Beta 3 gene and a molecular technique applied to these cells that can identify genetic differences which will allow the cloning of differentially expressed genes. The gene fragments that are identified will first provide clues as to what the genes are that maybe switched on or off to allow the tumour to grow beneath the skin. They will also form the basis of a Ometastatic melanoma gene panelO that can be tested for its diagnostic value of tumours. The utility and reproducibility of the gene panel will be confirmed by testing melanoma cell lines and tumour tissue. These experiments should lead to better diagnosis of metastatic melanoma and also possible new avenues to develop therapies for the disease.Read moreRead less
Novel Strategies In Cancer Cell Invasion In High-density 3D Matrix
Funder
National Health and Medical Research Council
Funding Amount
$60,768.00
Summary
The use of high-density (HD) matrix to study cell invasion sets precedence in mimicking the HD breast tissue condition that pose a real cancer risk. Cell invasion promotes the spread of cancer causing organ failures and death. The aims of this project are to determine the molecular mechanisms and to isolate new regulatory markers of cell invasion into HD matrix. Putative markers will be confirmed by investigating their expression levels in tissue arrays of 195 breast cancer samples.
Investigating Immune Regulation In The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
Suppressive factors made by cells of the immune system or cancers themselves and immune regulatory T cells inhibit an effective anti-tumour response. My project aims to investigate the mechanism by which these factors and cells mediate their suppressive function. Understanding these processes in the cancer environment will allow the design of more effective cancer therapies.
The Oncogenic Function Of A Histone H3K9 Demethylase And Its Contribution To The Aggressive Malignant Phenotype Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$762,501.00
Summary
In contrast to the significant improvements in the treatment of acute lymphocytic leukaemia, advances in acute myeloid leukaemia (AML) therapy have been limited. The difficulty in treating AML is thought to arise from a drug-resistant subpopulation of leukaemic stem cells (LSC) that are capable of reinitiating disease after chemotherapy. This project will characterise a key regulator of LSC and provide insights into an important oncogenic process that gives rise to the aggressive and often fatal ....In contrast to the significant improvements in the treatment of acute lymphocytic leukaemia, advances in acute myeloid leukaemia (AML) therapy have been limited. The difficulty in treating AML is thought to arise from a drug-resistant subpopulation of leukaemic stem cells (LSC) that are capable of reinitiating disease after chemotherapy. This project will characterise a key regulator of LSC and provide insights into an important oncogenic process that gives rise to the aggressive and often fatal AML.Read moreRead less
The Western Australia Malignant Pleural Effusions Management Study- What Factors Can Guide Management And Do Indwelling Pleural Catheters Represent The Best Treatment Option?
Funder
National Health and Medical Research Council
Funding Amount
$74,395.00
Summary
This randomised clinical trial will determine whether indwelling tunnelled pleural catheters are the best treatment strategy for patients with malignant pleural effusions. It will also look for ways in which the speed of fluid recurrence can be predicted. It will save public money by finding the most cost effective treatment strategies.
Novel Vaccine Formulation For Immunotherapy Of Adenocarcinomas
Funder
National Health and Medical Research Council
Funding Amount
$178,400.00
Summary
We have designed a vaccine based on a unique delivery system. Mice immunised with vaccine were protected from a tumour challenge. We will now design a vacine with a cancer associated protein so that people once immunised can make killer cells. Since humans have different genetic makeup we will produce a vacine which is more effective and will benefit everyone. This vaccine will be more effective than a current vacine in that has yielded promising results in humans.
Reactivities Of CD8 T Cells To Mutated Neo-antigens In Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
Tumours express mutated proteins (called ‘neo-antigens’) which can be targets of powerful killer T cells which can destroy cancer cells. To understand why these cells fail to cure most cancers we will study neo-antigens identified by modern DNA sequencing methods to identify these neo-antigens & the responses to them. Then it will be possible to design trials in individual patients, e.g. personalised vaccines to ‘force’ the immune system to attack cells bearing these neo-antigens.