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
PRECISION: Personalised Risk Evaluation In DCIS, International
Funder
National Health and Medical Research Council
Funding Amount
$1,392,930.00
Summary
Ductal carcinoma in situ (DCIS) of the breast is a common diagnosis with problematic clinical management. This study brings together an international consortium to identify and validate clinical biomarkers of recurrence.
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.
Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have b ....Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have been used extremely successfully in the treatment of some leukaemias. Unfortunately, retinoids have not worked as well in other cancers. We have identified an important role for abnormal retinoid function in the evolution of pancreatic cancer, which may be responsible for the lack of effective response to retinoid treatment. This project focuses on identifying if these abnormalities in retinoid function can be reversed with adding specific pharmaceuticals so that retinoid based therapies will be effective in pancreatic cancer.Read moreRead less
Role Of Cyclin E2 In Hormone-responsive Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$328,194.00
Summary
The female hormone estrogen stimulates the growth of breast cancers by promoting cell reproduction. We have found that cyclin E2, which is part of the machinery that controls cell reproduction, responds to estrogen. Since abnormally high levels of cyclin E2 are linked with earlier relapse in breast cancer, we wish to understand what role it plays in estrogen action and in breast cancer, how its levels are controlled, and whether too much cyclin E2 interferes with drugs that block estrogen action
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
Gastrokine 2: A Novel Stomach-specific Tumour Suppressor Gene
Funder
National Health and Medical Research Council
Funding Amount
$342,735.00
Summary
We will evaluate how a natural protein called gastrokine 2 acts to prevent cancer from developing in the stomach. We will show how gastrokine 2 interacts with another stomach protein TFF1, to block the effects of the inflammatory and cancer causing bacterium Helicobacter pylori, and the way that this bacterium circumvents this by turning off the production of gastrokine 2. Finally a drug which inhibits stomach tumour growth by turning on gastrokine 2 will be tested.
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