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Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have now shown that the gene Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we will examine how disruption of Scribble promotes cancer using a combination of tissue culture studies and a newly established mouse model. Understanding how this new pathway can regulate tumour development may provide novel targets for therapeutic intervention in cancer.
Expression And Functional Studies On The Novel Ovarian-expressed Serine Protease, Kallikrein 4, In Ovarian Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$410,250.00
Summary
Ovarian cancer is the leading cause of death from gynaecologic malignancies. In Australia, it is the most life-threatening of all gynaecological cancers. The major reason why the death rate has improved little in the last two decades is that ovarian cancer is detected too late and the type of treatment is not very effective. In this research, we are looking at a new protein, called the K4 protein, which belongs to the same family as the PSA enzyme that is used in the PSA test for prostate cancer ....Ovarian cancer is the leading cause of death from gynaecologic malignancies. In Australia, it is the most life-threatening of all gynaecological cancers. The major reason why the death rate has improved little in the last two decades is that ovarian cancer is detected too late and the type of treatment is not very effective. In this research, we are looking at a new protein, called the K4 protein, which belongs to the same family as the PSA enzyme that is used in the PSA test for prostate cancer. Our preliminary findings suggest that K4 is increased in the serous type ovarian cancer tumours so we intend to determine if K4 will be a useful bio-marker for this type of ovarian cancer. We also have made some interesting findings of some novel forms of the K4 protein and gene in ovarian cancer tissues and we intend to characterise these further to see if they might also be useful in detection of this disease. We are also studying the function and localisation of these different forms of K4 in cancer cells, to identify the exact role the enzyme performs in cancer development. These latter studies will help us understand the disease process better and may help us design new treatment approaches.Read moreRead less
A Lineage Specific Pathway For Progression Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$485,746.00
Summary
Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastas ....Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastasis of melanoma. These markers could serve as an important diagnostic marker for melanoma. Further, they may be suitable drug targets for the prevention and treatment of metastatic melanoma, and will advance our understanding of how melanoma spreads.Read moreRead less
Bombesin Like Peptides As Autocrine Growth Factors In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now kn ....Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now known as GRP in mammalian systems, is an established growth factor in certain lung cancers but little is known about its role in tumours of the large bowel. We will study the expression and production of GRP and its receptors at the gene and protein level, the ability of GRP to stimulate growth, the chemical structures of GRP, and the potential of antagonists of GRP to modulate growth. Studies will be performed in patients with bowel cancer, in animal models of bowel cancer, and with bowel tumours removed from patients and bowel cancer cell lines. A successful outcome will result in the development of assays for the early diagnosis and monitoring of bowel cancer and the potential for novel treatments such as GRP receptor antagonists and radiolabelled GRP analogues for radiotherapy.Read moreRead less
The majority of deaths from cancer are due to metastasis, which is the formation of secondary tumours at sites remote from the primary tumour. Metastasis involves conversion of some tumour cells to an invasive, migratory form in a process that is controlled by small genetic regulators known as microRNAs. In this project we will conduct experiments aimed to provide a proof of principle demonstration in mice that microRNAs can be used to block the formation of metastases.
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
Molecular Markers Of Phenotype, Therapeutic Responsiveness And Prognosis In Human Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$11,762,117.00
Summary
This proposal aims to identify molecular markers that can be used to classify subtypes of particular cancers according to their prognosis and response to therapy. This will optimise selection of patients for the most appropriate treatment and lead to the development of new therapeutic strategies.
A Fluorescent Zebrafish Model Of Endodermal Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
The most catastrophic event in cancer progression is when individual cancer cells move to other areas of the body and develop into secondary tumours. This very complex process shows striking similarities to cell movements during embryogenesis. In this project, we use a model system, the zebrafish, to analyse how cells move during embryogenesis. We will determine the genes required for cell movements in the zebrafish embryo, so we can find the corresponding genes in human cancers.
The Pez-TGFbeta-miR200-ZEB1-2 Axis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
A feature of late-stage cancer is metastasis - the dissemination of cancer cells to other tissues. Despite advances in treatment of primary cancers, metastatic disease remains the major cause of death in cancer patients. In metastatic cancers, the cells undergo a change that enables them to initially invade the surrounding tissues. We have discovered a novel regulator of the invasive process in tissue culture and this study aims to substantiate its role in breast cancer.
The Role Of Thymocyte Self-renewal In Causing T Cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$586,594.00
Summary
Recurrence of acute leukamia after therapy is due to the presence of immature cells that can self-renew, a process that is normally restricted to stem cells. Through the study of mice that develop leukaemia, we have identified these very rare self-renewing cells that are resistant to standard therapies. We can identify and measure these cells many months before leukaemia develops. As such, we will use this mouse model to understand how these cells self-renew and how they can be killed