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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
Role Of SOCS3 In Mammary Gland Development And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$224,278.00
Summary
We are studying the role of a family of inhibitory molecules (SOCS) in breast tissue; these proteins have been established to have critical roles in the immune system and in regulating growth of the entire animal. We have demonstrated that one member of this family can block the action of the prolactin hormone and have recently obtained evidence that another member of this family, SOCS3, affects survival of breast cells. Furthermore, this protein leads to increased growth when overexpressed in b ....We are studying the role of a family of inhibitory molecules (SOCS) in breast tissue; these proteins have been established to have critical roles in the immune system and in regulating growth of the entire animal. We have demonstrated that one member of this family can block the action of the prolactin hormone and have recently obtained evidence that another member of this family, SOCS3, affects survival of breast cells. Furthermore, this protein leads to increased growth when overexpressed in breast cells. We propose to define the normal role of this gene in mouse mammary tissue and to examine the consequences of expressing the gene at high levels in the mammary glands of mice. Inappropriate expression of this gene may predispose humans to breast cancer. SOCS3 expression will be directly studied in a cohort of primary invasive breast cancers with associated clinical outcome data, to determine whether it has a role as a potential prognostic marker.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.
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
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
A Randomised Phase III Study Of Radiation Doses And Fractionation Schedules For Non-low Risk Ductal Carcinoma In Situ Of The Breast
Funder
National Health and Medical Research Council
Funding Amount
$658,419.00
Summary
After surgery to remove ductal carcinoma in situ (DCIS), a pre-invasive form of breast cancer, radiotherapy to the breast decreases the risk of recurrence. The study investigates if a higher radiation dose to the tumour bed improves tumour control, and if a shorter course of radiotherapy is as effective as the standard longer course. It also assesses quality of life consequences of treatment and tests biomarkers that may predict the risk of recurrence in individual patients.
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.
MMP13 is upregulated in cancer cells and in the tissue that forms around the cancer (stroma). A new MMP13-specific inhibitor reduces breast cancer growth in a mouse model, both at the primary site and also in bone. We will determine the role of MMP13 made by the cancer cells and stroma, respectively, extend the inhibitor work, and identify proteins being cleaved by MMP13. Being a late-stage manifestation, bone metastasis may represent an important clinical trial setting for MMP inhibitors.