Tailored Treatments For Premenopausal Women With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$299,213.00
Summary
For women <50yrs with ER+ breast cancer adjuvant treatment (AT) with chemotherapy (CT), tamoxifen and ovarian function suppression (OFS) are each effective and reduce recurrence. Combining 2 treatments is more effective than 1, but it is unclear if combining 3 provides any extra benefit. 2 trials,SOFT and TEXT, aim to answer this question. SOFT tests the benefit of adding OFS for very young women who remain premenopausal after CT, TEXT is for women who should receive OFS from the start of AT.
Tailored Treatments For Premenopausal Patients With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$257,250.00
Summary
For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been des ....For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been designed for adjuvant therapy of premenopausal women with ER+ breast cancer. These trials take into account regional-country variations in medical practice and different patient choices in this setting. SOFT is for very young women and tests the benefit of adding ovarian suppression in a woman who has received chemotherapy, with tamoxifen planned, but who has not gone into menopause after chemotherapy. The trial also tests if substituting a newer drug called exemestane for tamoxifen, combined with ovarian function suppression is more effective. TEXT is for women who would ordinarily be treated with ovarian suppression plus tamoxifen. The TEXT trial also tests substitution of exemestane for tamoxifen. Exemestane is an aromatase inhibitor. Aromatase inhibitors lower oestrogen levels, but only work if the ovaries are inactive. Recent trials in post menopausal women show aromatase inhibitors are more effective than tamoxifen, and we aim to replicate that improvement in younger women by combining exemestane with ovarian suppression. PERCHE is for women in whom the benefit of chemotherapy is uncertain, for example those with limited or no spread to lymph nodes. All women receive combined endocrine treatment with ovarian suppression plus tamoxifen, and are randomised to receive in addition, either chemotherapy or no chemotherapy, to see if results differ.Read moreRead less
Hormone Transport By Alpha-2-Macroglobulin: Novel Roles In Regulating Hormone Activity
Funder
National Health and Medical Research Council
Funding Amount
$602,857.00
Summary
Alpha-2-macroglobulin is a large protein in the blood known to bind and transport numerous hormones in the circulation. Our previous studies published in BLOOD (2009) and JBC (2013) have discovered an important role for this molecule in the transport and regulation of a peptide hormone. The studies proposed in this application have important implications for understanding new roles of alpha-2-macroglobulin in hormone binding and regulating the activity of hormones in disease states.
Obstructive Sleep Apnoea As A Risk Factor For Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Atrial fibrillation is the most common sustained cardiac arrhythmia and obstructive sleep apnoea is a common sleep-related breathing disorder. It has recently been suggested that OSA increases the risk of developing AF . The aim, therefore of this study, is to determine the incidence of sleep apnoea in our population of highly symtomatic patients with atrial fibrillation and to assess the outcome on arrhythmia burden of treatment with continuous positive airways pressure (CPAP).
The Role Of Ghrelin And Growth Hormone Releasing Hormone In The Autocrine Regulation Of Prostate Cancer Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in ....Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in regulating GH release. There is growing evidence that the GHRH-GH-IGF axis has a significant role in prostate cancer, but little is known about how this happens. We also have evidence that the ghrelin-GHS-R axis is involved in prostate cancer, as prostate cancer cell lines produce both ghrelin and the receptor through which it acts. Our preliminary studies show that ghrelin enhances cell growth in these cells. GHRH blocking agents (antagonists) are potential treatments for prostate cancer, as they slow the growth of prostate tumours. How they act is unclear, but they might interfere with a locally active GHRH pathway in the prostate. This study aims to explore the role of ghrelin and GHRH in prostate cancer. Since there is an increase in the use of GHRH, GH and-or IGF-I and potentially ghrelin for the treatment of a variety of medical conditions, including some in the aging male, the need for a fuller understanding of the role of this axis in prostate cancer is increasingly important. Such information will lead to a deeper understanding of the actions of ghrelin and GHRH and provide potential opportunities for design of new therapies for prostate and other GH-IGF-responsive tumours.Read moreRead less
Impact Of Progesterone Receptor Subnuclear Localisation On Progesterone Action In Endocrine Target Cells
Funder
National Health and Medical Research Council
Funding Amount
$459,514.00
Summary
Breast cancer affects 10,000 Australian women annually and is a major cause of cancer death. The hormone progesterone, which is produced by the ovaries in women, is responsible for some aspects of the development of the normal breast in women and is also implicated in the development and response of breast and endometrial cancers. In normal cells progesterone acts via a specific protein (or receptor) in the nucleus, and we have shown that this protein accumulates into foci when it is active. We ....Breast cancer affects 10,000 Australian women annually and is a major cause of cancer death. The hormone progesterone, which is produced by the ovaries in women, is responsible for some aspects of the development of the normal breast in women and is also implicated in the development and response of breast and endometrial cancers. In normal cells progesterone acts via a specific protein (or receptor) in the nucleus, and we have shown that this protein accumulates into foci when it is active. We have noticed that in cancers, this accumulation is disrupted, and this is a bad sign for the cancer. As breast cancer develops, it causes many dramatic changes in the structure of cells of the breast, and particularly in the nucleus, which carries the genetic information that programs cancer cell behaviour. The nucleus normally is highly organised into compartments, which carry out different functions of the cell, such as duplication of the DNA, repair of DNA after damage, and switching on and off of particular genes important to the function of the cell. This organisation is altered dramatically in cancer cells, and it seems that this altered organisation is responsible for altered function. In this project we aim to work out what makes the receptor for progesterone form foci, how these foci are involved in the action of progesterone, and how the changed structure of the nucleus changes this process. This project will link the structure of the cell nucleus with the ability of progesterone to switch on or off particular genes, and this will provide the first signposts of how changes seen in cancer cell nuclei are reflected in changed hormonal signalling. Healthy women are regularly exposed to progestins in oral contraceptives and hormone replacement therapy. The known increased risk of breast cancer as a result of exposure to progestins creates an imperative to understand how progesterone may have aberrant effects. This project will address this important health issue.Read moreRead less
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.