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DETECTION OF OCCULT DISSEMINATED TUMOUR CELLS AND TUMOUR DNA IN EARLY STAGE OPERABLE BREAST CANCER PATIENTS
Funder
National Health and Medical Research Council
Funding Amount
$561,000.00
Summary
Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant ....Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant risk of under treating good prognosis disease patients (20%) and over treating women with intermediate and high risk disease (40%). The first aim of the study is to use novel molecular methodologies to detect breast cancer cells in the blood of patients with early stage breast cancer at diagnosis. The presence of tumour cells will be correlated with the usual prognostic factors used in the management of women with breast cancer. The patients will be followed long-term to clarify the relationship between disseminated tumour cells in the blood and bone marrow and eventual outcome to assess the effectiveness of these new methodologies in patient management. We will also assess new molecular methodologies which will allow us to track very low levels of disease, and thereby monitor the effectiveness of treatment, and allow prediction of impending relapse. Studying the blood of breast cancer patients represents a unique opportunity for determining whether the cancer has spread before surgery and for monitoring of disease after surgical removal of the tumour. This study may prove invaluable in predicting disease free and survival outcomes and provide a more rational approach to the use of chemotherapy in patients with early breast cancer.Read moreRead less
Mechanisms Of Action Of The Zinc Finger Protein LMO4 In Breast Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$272,859.00
Summary
Breast cancer is the most common cancer to strike Australian women, affecting one in 12 women by age 75. Although treatment of breast cancer has substanially improved over the last few years, approximately 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of new effective therapeutic inhibitors of canc ....Breast cancer is the most common cancer to strike Australian women, affecting one in 12 women by age 75. Although treatment of breast cancer has substanially improved over the last few years, approximately 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of new effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes that contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. We are particularly interested in 'master regulators' that are located in the cell nucleus. Nuclear regulators have been implicated in many different types of cancer and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their biological roles and mechanism of action, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific nuclear regulatory molecule, LMO4, which we have demonstrated to be overexpressed in 56% of human primary breast cancers. Significantly, we have recently shown that overexpression of LMO4 predicts poor outcome in breast cancer patients. We have also shown that this protein interacts with the breast tumour suppressor protein BRCA1, as well as a number of other proteins. These studies will include defining LMO4 s role in governing cell growth in breast cancer cells and that of the proteins that bind to this regulator. We will also assess the role of LMO4 in controlling cell invasion and metastasis of breast cancer cells in mouse models since we have preliminary evidence that it may be a critical regulator of these processes.Read moreRead less
Proteomic Screening For Apoptotic Markers In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell li ....The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell lines showed time-dependent decreases in two proteins, identified as S100A6 and ubiquitin. Both are known to be important in cell function. In the proposed project we will build on our preliminary findings to provide important new information central to the understanding of cancer cell biology and apoptosis in addition to evaluating the ability of anti-cancer treatments to induce apoptosis. Using a combination of protein analysis technologies, this project has the potential to provide reliable and novel biomarkers which will indicate the efficacy and selectivity of anti-cancer treatments in inducing tumour cell death. The knowledge gained in this project will aid clinical assessment of the response to cancer treatment(s) in patients in the form of specific screening assays, and may result in identification and development of effective new agents for cancer treatment and prevention. Furthermore, the outcomes of this project will increase our understanding of fundamental cancer cell biology and apoptosis.Read moreRead less