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
Epigenetics is a term that describes modification of gene expression without a change to the DNA sequence, through processes that involve chemical changes to the DNA such as DNA methylation and binding of specific proteins. It is now well established that epigenetics plays a major role in cancer development, but one of the important questions still to be resolved is the mechanism that is responsible for epigenetic changes. Our recent work has uncovered a new mechanism of epigenetic gene silencin ....Epigenetics is a term that describes modification of gene expression without a change to the DNA sequence, through processes that involve chemical changes to the DNA such as DNA methylation and binding of specific proteins. It is now well established that epigenetics plays a major role in cancer development, but one of the important questions still to be resolved is the mechanism that is responsible for epigenetic changes. Our recent work has uncovered a new mechanism of epigenetic gene silencing in cancer that can effect large chromosomal regions. We have found that both methylated and unmethylated genes can be silenced by changes to the pattern of proteins that bind to the DNA in a cancer cell. Our data also indicates that this silencing can be reversed using epigenetic drugs. This finding represents a new paradigm in epigenetic control and has major implications not only on cancer diagnostics but also cancer epigenetic therapy. In this grant we propose to further characterise and understand the mechanism involved in long range epigenetic silencing and to determine its prevalence in cancer. This proposal will shed light onto the process underlying long range epigenetic gene silencing in cancer and will provide potential novel targets for cancer detection, prognosis and therapy.Read moreRead less
Determination Of Diagnostic Molecular Profiles For Intraduct Lesions Of The Breast.
Funder
National Health and Medical Research Council
Funding Amount
$308,400.00
Summary
Breast cancer originates in cells within breast ducts. The introduction of Breast Screening for breast cancer has led to a dramatic increase in the diagnosis of breast cancer which is confined to these ducts and has not spread to surrounding tissue. This is known as 'ductal carcinoma in situ' or DCIS. It is evident that DCIS is variable in its tendency to give rise to more advanced breast cancer. However, currently our ability to predict the potential agressiveness of a particular DCIS is limite ....Breast cancer originates in cells within breast ducts. The introduction of Breast Screening for breast cancer has led to a dramatic increase in the diagnosis of breast cancer which is confined to these ducts and has not spread to surrounding tissue. This is known as 'ductal carcinoma in situ' or DCIS. It is evident that DCIS is variable in its tendency to give rise to more advanced breast cancer. However, currently our ability to predict the potential agressiveness of a particular DCIS is limited. In this research we are proposing to develop new methods for evaluation of DCIS that will more accurately predict clinical behaviour. An important adjunct is to ensure that these methods can be practically applied in a routine diagnostic setting. Achievement of the aims of this project will assist treatment planning for patients diagnosed with DCIS. It will also provide important information about breast cancers diagnosed as a consequence of breast screening.Read moreRead less
Detection of infrared-biomarkers for the diagnosis and treatment of canine neoplasia. This research hopes to discover infrared-biomarkers for canine cancers using synchrotron infrared and laser light. Many dog cancers are similar to human cancers so cancerous tissues and cells from dogs make excellent models for human cancer research. This project will provide new insights and technological approaches to cancer diagnosis and treatment.
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
Caged lanthanides for use in photo-dynamic therapy and near infra-red imaging. The early detection and effective treatment of cancer are two critical factors which determine survivability. This project will provide improved drugs for photo-dynamic therapy and develop emissive probes for near infra-red imaging to allow better discrimination between healthy and diseased tissue and improve subsequent treatment.