How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Integrated Analysis And Functional Characterisation Of Gene Amplicons In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$453,068.00
Summary
In Australia in 2001 there were ~1300 new cases of ovarian cancer. Survival of ovarian cancer is very poor and current treatments inadequate. To develop more effective treatments we need to understand the molecular events that cause ovarian cancer. Some genes have multiple copies in ovarian cancer cells and these may be good targets for therapy. We aim to find these genes and determine which ones have a functional effect in the tumour.
Downregulation Of N-myc Oncogene Expression As A Therapeutic Strategy For Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$145,990.00
Summary
Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients ....Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.Read moreRead less
Cohesin Dysfunction: Potential New Route To Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$386,511.00
Summary
This proposal aims to investigate the role of a newly-discovered chromosomal and DNA repair protein, Rad21, in breast cancer. Rad21 is a gene, present in many species and essential for accurate chromosome separation. Based on its' known function in different species, it is conceivable that its' dysfunction could fuel cancer progression by promoting genetic instability, eg. gains or losses of chromosomes, commonly associated with human cancers. No definitive data currently exists as regards the p ....This proposal aims to investigate the role of a newly-discovered chromosomal and DNA repair protein, Rad21, in breast cancer. Rad21 is a gene, present in many species and essential for accurate chromosome separation. Based on its' known function in different species, it is conceivable that its' dysfunction could fuel cancer progression by promoting genetic instability, eg. gains or losses of chromosomes, commonly associated with human cancers. No definitive data currently exists as regards the potential role of this gene in cancer development. This study is thus the first systematic investigation towards understanding the function of this potential cancer-causing gene. Although the proposed study focuses on breast cancers, it could, in principle, apply to other cancer types in which its' overactivity has recently be oberserved. This study could also have implications for the response of humans to radio- and chemo-therapy for cancer treatmentRead moreRead less
RNA Polymerase I: A Novel Target In The Treatment Of MYC Driven Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is dysregulated during cancer leading to the hypothesis that it may be causative in the malignant process. This application will test this hypothesis using novel inhibitors or ribosome biogenesis in a mouse genetic model termed E�-MYC that faithfully that replicates human B-cell lymphoma. These studies will uncover novel mechanisms in malignant transformation and identify new therapeutics in the treatment of human cancer.
Serum Mesothelin-related Protein As An Early Marker Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$354,750.00
Summary
The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. It is expected to cost communities hundreds of billions of dollars in compensation. This disease is usually already quite advanced by the time a patients presents to a doctor with symptoms so we have been working on methods of early detection. This project studies a new, exciting method of diagnosis using blood levels of a molecule called 'SMRP'. Late l ....The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. It is expected to cost communities hundreds of billions of dollars in compensation. This disease is usually already quite advanced by the time a patients presents to a doctor with symptoms so we have been working on methods of early detection. This project studies a new, exciting method of diagnosis using blood levels of a molecule called 'SMRP'. Late last year we published a paper in the prestigious journal Lancet showing that SMRP was a good test to help diagnose mesothelioma and this became a lead news item around the world because of widespread concern about this disease. In those studies we found strong clues that this test was very sensitive and could detect mesothelioma a year or so before a patient develops symptoms. In this grant we will evaluate whether this test could be useful for screening asbestos-exposed individuals for early detection of this cancer. We will also study ways of improving the test using laboratory methods. This would provide a foundation for studies aimed at determining if early treatment could improve patient survival.Read moreRead less
Genetic Polymorphisms In Genes Controlling Innate Immunity As Risk Factors For Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$241,500.00
Summary
For some time now, researchers have speculated that the development of childhood leukaemia is related to exposure to an infectious agent. However, a causal pathogen is yet to be identified. Recent studies have shown that the initial recognition of microbes as they enter the human body is determined by a group of receptors, toll-like receptors (TLRs), which selectively bind to essential components of these pathogens. This process allows the body to respond immediately to microbial invasion; a pro ....For some time now, researchers have speculated that the development of childhood leukaemia is related to exposure to an infectious agent. However, a causal pathogen is yet to be identified. Recent studies have shown that the initial recognition of microbes as they enter the human body is determined by a group of receptors, toll-like receptors (TLRs), which selectively bind to essential components of these pathogens. This process allows the body to respond immediately to microbial invasion; a process which is vital during early childhood, when clonal expansion of antibodies and other host defences is inadequate. It is becoming increasingly apparent that this innate immune response is not just the first line of defence but a necessary event for the development of an adaptive immune response. We propose that the innate immune system of children carrying TLR gene variants may be less effective at detecting the presence of microbial pathogens in the environment. We hypothesize that by dampening the stimulation of innate immunity in early childhood, TLR gene variants may indirectly cause a dysfunction in the maturation of a child's immune system and increase the chance of a pre-leukaemic clone emerging, leading to the development of childhood leukaemia.Read moreRead less
A Record Linkage Study Of The Relationship Between Intra-uterine Growth, Birth Weight And Childhood Acute Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$126,000.00
Summary
Little is known about the causes of childhood leukaemia and cancer, and this has been the subject of intense study over many years. Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML) are the most common types of childhood cancers. The early age of onset of diagnosis of cancer-leukaemia in childhood has focused attention on factors related to pregnancy. Many studies have investigated the relationship between birth weight and risk of leukaemia. Some studies have reported finding ....Little is known about the causes of childhood leukaemia and cancer, and this has been the subject of intense study over many years. Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML) are the most common types of childhood cancers. The early age of onset of diagnosis of cancer-leukaemia in childhood has focused attention on factors related to pregnancy. Many studies have investigated the relationship between birth weight and risk of leukaemia. Some studies have reported finding an increasing risk of Acute Lymphoblastic Leukaemia with increasing birth weight, but not all studies have reported this relationship. The relationship between birth weight and Acute Myeloid Leukaemia has been even less well described. Many previous studies have not taken account of important factors when analysing the results. This study will use an existing pool of routinely recorded health information, thus ensuring accurate information on birth weight and factors such as maternal height and age and the length of the pregnancy. We will also have complete and accurate information on childhood cancer in Western Australia. Our results will contribute to knowledge about the causes of childhood leukaemia and the biological pathways involved in its development. If growth-related factors do prove to be integrally involved in the aetiology of childhood leukaemia, then the rapidly increasing prevalence of juvenile diabetes, overweight and obesity in Australia and other developed countries could have even more serious implications for the health of our children. It is important that we investigate this question as soon as possible.Read moreRead less
Development Of A Specific Activin Antagonist For Therapeutic Applications
Funder
National Health and Medical Research Council
Funding Amount
$504,287.00
Summary
Activin is a key regulator of homeostasis in several organs and tissues, including ovaries, testes, liver and skin, and alterations in activin�s activity can result in fibrosis, cachexia and cancer. In this grant we propose to develop a specific activin antagonist by modifying the activin A propeptide. This novel reagent could be used to promote liver growth in severe hepatic disease and prevent fibrosis in numerous tissues.
Is Hypoxia Inducible Factor 2 The Trigger Of The Angiogenic Switch And A Driver Of Disease Progression In Myeloma?
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Multiple myeloma (MM) is a fatal cancer of plasma cells (PC). PC migrate to the bone marrow, which compared with other organs is low in oxygen (hypoxic). In response to this hypoxia, the cancer cells turn on the expression of genes called hypoxia-inducible factors (HIF). HIFs activate the expression of genes that encourage blood vessel formation, which in turn stimulates greater tumour growth and disease progression. This proposal will investigate the role of HIFs in the progression of MM.