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Differentiation Therapy Of Acute Myeloid Leukaemia: Combining RAR-agonists And G-CSF.
Funder
National Health and Medical Research Council
Funding Amount
$449,500.00
Summary
The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human le ....The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human leukemia cells grown in the laboratory. By deleting the genes for MAD1 and p27KIP1 we will determine if leukaemias lacking these genes fail to respond to treatments targeting the retinoic acid receptor alpha. We will also test if treatments that target retinoic acid receptors in combination with G-CSF, a protein that has previously been demonstrated to have anti-leukaemic activity, can work together to block growth of leukaemic and genetically modified cells. Together these studies will help define classes of leukamias that either will or will not respond to treatments aimed at retinoic acid receptor to better target future leukemia treatments.Read moreRead less
Molecular Profiling Of Breast Tumour Stem/Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$308,824.00
Summary
Breast cancer is the commonest cancer in women in many countries including Australia, the USA and the UK. The incidence of breast cancer has been increasing over the last decade however mortality from breast cancer has declined. Although there is debate as to the exact reasons for this decline in mortality, it is clear that the introduction of the screening program as well as improvements in treatment have played a significant role. Nevertheless, a proportion of patients will have disseminated d ....Breast cancer is the commonest cancer in women in many countries including Australia, the USA and the UK. The incidence of breast cancer has been increasing over the last decade however mortality from breast cancer has declined. Although there is debate as to the exact reasons for this decline in mortality, it is clear that the introduction of the screening program as well as improvements in treatment have played a significant role. Nevertheless, a proportion of patients will have disseminated disease at presentation and may not fully respond to treatment. In addition a number of patients will go on to form apparent recurrence of the primary tumour and- or distant metastases following what appears to be complete clearance of a tumour. In recent years a new concept has been put forward that might account for some of these recurrences. It is thought that the cells in a tumour do not all divide at the same rate. Instead some cells only divide rarely, and then give rise to other cells which divide rapidly and form the bulk of the tumour. Since these 'tumour stem cells' are slow cycling they will be resistant to existing chemotherapy because this affects rapidly dividing cells. These resistant cells may then go on to form another tumour. We intend to study these 'tumour stem cells' using a range of techniques that will show us how they differ from both the rest of the tumour cells and the different types of normal cells in the breast. By identifying molecules that are different in the tumour stem cells we will then have new targets for therapies that are designed to target these chemotherapy-resistant cells. Such therapies could be used in the future in conjunction with existing therapies to achieve a greater eradication of breast tumours.Read moreRead less
Identification Of Oncogenes From Myeloid Leukaemias By Retroviral Expression Cloning
Funder
National Health and Medical Research Council
Funding Amount
$552,000.00
Summary
The success rates for treatment of most myeloid leukaemias remain relatively poor, with 5-year survival rates of 40-50% overall. Thus there is a clear need for improvements in diagnosis and particularly treatment. An important and relatively new approach for doing this is to target the specific molecular and genetic alterations that lead to these diseases. This requires the identification of these alterations, particularly the oncogenes ('cancer genes') that cause or contribute to the various fo ....The success rates for treatment of most myeloid leukaemias remain relatively poor, with 5-year survival rates of 40-50% overall. Thus there is a clear need for improvements in diagnosis and particularly treatment. An important and relatively new approach for doing this is to target the specific molecular and genetic alterations that lead to these diseases. This requires the identification of these alterations, particularly the oncogenes ('cancer genes') that cause or contribute to the various forms of myeloid leukaemia. However in many cases (up to 50%), the key oncogenes involved in have not and-or cannot be identified using current methods. This project aims to develop and apply a powerful technique called 'retroviral expression cloning' for the identification of oncogenes involved in myeloid leukaemia. In essence our approach is to identify oncogenes from myeloid leukaemia samples on the basis of their function - that is, by virtue of their ability to induce dysregulated or uncontrolled growth of blood-derived cells in culture.Read moreRead less
APC Mutation And The Initiation Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,267.00
Summary
Colorectal (or bowel) cancer is a major health problem in Australia. At present it is the most common cancer, approximately 1 in 21 Australians will develop the disease in his-her lifetime. The risk of bowel cancer increases with age, with the risk rising progressively and sharply from the age of 50. Current therapies for advanced colorectal cancer are not very effective. Mortality from colorectal cancer is high, being second only to lung cancer as the leading cause of cancer death in Australia. ....Colorectal (or bowel) cancer is a major health problem in Australia. At present it is the most common cancer, approximately 1 in 21 Australians will develop the disease in his-her lifetime. The risk of bowel cancer increases with age, with the risk rising progressively and sharply from the age of 50. Current therapies for advanced colorectal cancer are not very effective. Mortality from colorectal cancer is high, being second only to lung cancer as the leading cause of cancer death in Australia. The development of colorectal cancer is affected by both genetic and environmental factors. Colorectal cancer progresses through a number of distinct pathological stages. This is thought to be the result of the progressive aquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations in a gene known as APC are associated with the very early stages of tumour formation in at least 80% of colorectal tumours. Our research is aimed at understanding how alterations in APC influence the behaviour and growth of colonic cells. We have developed a novel system where normal mouse colon can be maintained and grown for up to 2 weeks in a Petri dish. Alterations in the APC gene and other colon cancer genes will be introduced into the normal epithelial cell lining and the effects on the growth and behaviour of the cells in organ culture will be analysed. Our hypothesis is that changes in the APC gene affects the way cells migrate, divide and move. This work should improve our knowledge of the cellular changes that occur during tumour initiation in the bowel and aims to contribute to the design of new therapies for early intervention in colon cancer.Read moreRead less