Characterising The Beneficial Effects Of Estrogen On The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$594,722.00
Summary
Prostate cancer is hormonally regulated and currently managed by androgen ablation. This application seeks to study the potential benefits of estrogen action for the treatment of prostate disease, including PCa. We will show estrogen hormone action causes prostatic cell death, targeting the stem-progenitor cells so the treated prostatic tissue does not regenerate. This project will provide pre-clinical proof of the efficacy of estrogenic compounds as a potential therapy for prostate disease.
Using Genetically Manipulated Mice To Study The Pathophysiologic Consequences Of Castration-induced Prostatic Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
Prostate cancer is the second leading cause of cancer death among Australian men. The disease is incurable once it spreads beyond the confines of the prostate gland. Hormonal treatments can keep the cancer at bay for a number of years until they are no longer effective. Hormonal treatments cause shrinkage of prostate cancer because they interfere the function of the male hormone, testosterone, which encourages growth of prostate cancer. Hence, there is a need for other treatments that may improv ....Prostate cancer is the second leading cause of cancer death among Australian men. The disease is incurable once it spreads beyond the confines of the prostate gland. Hormonal treatments can keep the cancer at bay for a number of years until they are no longer effective. Hormonal treatments cause shrinkage of prostate cancer because they interfere the function of the male hormone, testosterone, which encourages growth of prostate cancer. Hence, there is a need for other treatments that may improve the quality of life and survival of prostate cancer patients. It appears that a cancer patient can make immune cells known as T cells, which can recognise his own tumour but which are prevented from destroying the tumour. Using a mouse model of prostate cancer, we wish to understand how prostate tumours act to prevent immune destruction in circumstances that are common to the treatment of human prostate cancer. For example, hormonal treatments produce dead prostate cancer cells that will be cleared by the body's professional scavenger cells in a way that suppresses an active immune response against the tumour. To learn how the removal of dead cells suppresses the immune response, we propose to perturb the normal clearance of dead prostate cells by at least two means. First, we will study mice that have an inherited deficiency in the removal of dead cells. Second, these mice will be given a growth factor to produce an excess of immune stimulating cells known as dendritic cells in the prostate gland. The dendritic cell is the main type of cell that initiates immune responses. We will investigate whether the greater number of dendritic cells, which were put into the prostate gland by the growth factor, can remove the dead prostate cells in a way that excites rather than suppresses the anti-tumour immune response. Positive results obtained from these studies may lead to the design of new treatments for advanced prostate cancer.Read moreRead less
Risk Factors, Screening, Prophylaxis And Outcomes In Individuals From Breast Cancer Families: KConFab Follow-Up Study
Funder
National Health and Medical Research Council
Funding Amount
$510,675.00
Summary
Having a strong family history of breast cancer is one of the most important risk factors for the disease. Two major genes, BRCA1 and BRCA2, have been identified which, when abnormal, result in an inherited tendency towards developing breast cancer. Women with a strong family history of breast cancer can undergo testing for these gene abnormalities via Family Cancer Centres around Australia. However, once a gene abnormality is found, little is known about the best ways to prevent cancer or detec ....Having a strong family history of breast cancer is one of the most important risk factors for the disease. Two major genes, BRCA1 and BRCA2, have been identified which, when abnormal, result in an inherited tendency towards developing breast cancer. Women with a strong family history of breast cancer can undergo testing for these gene abnormalities via Family Cancer Centres around Australia. However, once a gene abnormality is found, little is known about the best ways to prevent cancer or detect it early. The Kathleen Cuningham Consortium for Research into Familial Aspects of Breast Cancer (kConFab) has been recruiting families with exceptionally strong histories of breast cancer since 1997. kConFab is funded to collect epidemiological information and biological specimens on such individuals only at the time of their initial recruitment. In 2000 the NHMRC recognised the importance of undertaking clinical follow-up of this precious cohort of individuals, and provided funding through a 3 year project grant to commence the first round of 3 yearly follow-up on this cohort (NHMRC Project Grant #145684). The first 2 years of this follow-up has been completed successfully and the current is application is for a renewal of funding (to commence in 2004) to enable us to undertake further follow-up of the now much larger cohort. In the short term we will examine the screening and preventive surgery behaviours of high risk women within this study to determine whether they are optimal. The ultimate aim of this long term follow-up of individuals in kConFab is to determine what factors impact on the development of cancer in well individuals with a genetic predisposition to breast cancer.Read moreRead less
Modulation Of Cytoskeletal Structure By Progesterone Receptor Isoforms
Funder
National Health and Medical Research Council
Funding Amount
$337,650.00
Summary
Ovarian hormones are fundamental regulators of normal cell growth and differentiation, and crucial to the development and progression of breast cancer. We have recently shown that the ovarian hormone progesterone can influence the expression of proteins in the cell scaffolding, known as the cytoskeleton. The cytoskeleton is responsible for maintaining cell shape, and there is growing evidence that alterations in the cytoskeleton can actually cause normal cells to become cancerous. We have shown ....Ovarian hormones are fundamental regulators of normal cell growth and differentiation, and crucial to the development and progression of breast cancer. We have recently shown that the ovarian hormone progesterone can influence the expression of proteins in the cell scaffolding, known as the cytoskeleton. The cytoskeleton is responsible for maintaining cell shape, and there is growing evidence that alterations in the cytoskeleton can actually cause normal cells to become cancerous. We have shown that progesterone affects the levels of a cytoskeletal protein called tropomyosin, which plays a pivotal role in cell shape maintenance. We have hypothesised that this effect may be important in the cell shape changes in breast cancer that lead to metastasis. In this grant, we will investigate the role of the progesterone receptor in controlling the expression of the cytokeleton; we will investigate whether cell shape changes caused by progesterone cause more aggressive behaviour in breast cancer cells and we will determine whether there are changes in cytokeletal proteins in breast tumours. This will provide a rational basis for further studies aimed at delineating the significance of hormonal regulation of cell architecture.Read moreRead less
Genome-wide Expression Analysis In Advanced Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$326,761.00
Summary
Gastric cancer is the fourth ranked cancer by mortality in Australia. Therapy of gastric cancer is unsatisfactory for two reasons; firstly, how normal stomach cells become cancerous is not well defined. We know long-term infection with the bacteria Helicobacter can lead to these cancers, as can severe acid reflux. The cancers produced by these very different agents look remarkably similar, but must be arising through different pathways. Research to date has not yielded great insight. Secondly, e ....Gastric cancer is the fourth ranked cancer by mortality in Australia. Therapy of gastric cancer is unsatisfactory for two reasons; firstly, how normal stomach cells become cancerous is not well defined. We know long-term infection with the bacteria Helicobacter can lead to these cancers, as can severe acid reflux. The cancers produced by these very different agents look remarkably similar, but must be arising through different pathways. Research to date has not yielded great insight. Secondly, existing therapy, especially chemotherapy, tends to provide a Oone size fits all? solution. Whatever the cause, removal at surgery is the best option for treatment. After this, patients are often treated with chemotherapy. Although improvements in patient comfort have been made, very few patients are cured as a result of this treatment. We need more information with which to match the right patient with the right therapy. We will perform high-throughput analysis of comprehensive arrays of human genes that are affected in gastric cancer. Biopsies from cancerous and normal tissue will be obtained when patients have surgery. This tissue will have the RNA (the Omessage? from each gene) labelled with chemical tags and then applied to DNA Omicrochips?. Each microchip contains about 5000 gene targets; the RNA binds the matching DNA and produces a light reaction. We can read the light output from these 5000 (or more) signals, and perform complex statistical analysis on the results. This will result in several specific Ogene expression profiles? which we will analyse to see which profiles match each situation. Profiles matching reflux-induced cancer and Helicobacter-induced cancer can be compared. This will suggest what unique processes are occurring in the cancer cells. Profiles of patients responding well to therapy may allow the use of Otailor-made? therapy. In the future, insight into cancer pathways should also allow the design of new and more successful therapies.Read moreRead less
Integrating Conventional Mesothelioma Therapies With Immuno- And Gene-therapies
Funder
National Health and Medical Research Council
Funding Amount
$804,916.00
Summary
Asbestos-induces cancers are some of the most aggressive cancers know to medicine. Unfortunately, treatments are not very effective and it is unusual for these cancers to be cured, particularly mesothelioma. Because recent scientific studies have suggested that combinations of therapy which include immunotherapy, ie treatments aimed at stimulating the bodies anti-cancer immune responses to attack the cancer, can be effective, we plan to develop this work in order to determine exactly which combi ....Asbestos-induces cancers are some of the most aggressive cancers know to medicine. Unfortunately, treatments are not very effective and it is unusual for these cancers to be cured, particularly mesothelioma. Because recent scientific studies have suggested that combinations of therapy which include immunotherapy, ie treatments aimed at stimulating the bodies anti-cancer immune responses to attack the cancer, can be effective, we plan to develop this work in order to determine exactly which combinations are likely to be the most effective and therefore the most suitable for clinical trial in patients.Read moreRead less
Identification And Molecular Characterisation Of High-risk Premalignant Breast Lesions
Funder
National Health and Medical Research Council
Funding Amount
$560,382.00
Summary
Understanding the full repertoire of genetic events that underlie the development of breast cancer may allow development of prevention strategies. This study will analyse genetic data of benign breast lesions that may be non-obligate precursors of breast cancer. Importantly, clinical management of these lesions is difficult. A reliable method of predicting the risk of progression to cancer would be a significant advance, with benefits to individual patients and also the health system.
Intraprostatic Androgen Signalling As A Target In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Male hormones (androgens) are the fuel that drives prostate cancer so reducing androgen levels is the standard treatment but cant cure the disease and causes serious side-effects throughout the body. We need to better target androgen withdrawal to prostate cancers and learn more about how it works to improve treatment. This project utilizes unique mouse models for experiments not feasible in humans to learn how androgens act and can be better targeted to cure prostate cancers.