This project will test the proposal that rising follicle-stimulating hormone (FSH) levels in ageing females directly accelerate reproductive failure and bone loss , major public health issues due to delayed childbearing and our rising ageing population. We have developed a unique mouse model with elevated FSH levels that cause premature female infertility. We will now use this model to determine the direct effects of high FSH upon ovarian and uterine function, as well as bone loss with age.
Hormonal Influences In The Pathogenesis Of Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$264,601.00
Summary
Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In orde ....Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In order to identify these genes we will draw on our knowledge of the genes that are important in the controlof growth and hormone secretion in normal ovarian cells. To assist this molecular analysis we will use two ovarian cell lines in culture that have many of the features of the primary tumours including inhibin secretion. We will also use new techniques to scan over 500 genes involved in tumours in general to see whether we detect any unusual or distinctive patterns in this sub-group of tumours. A genome wide scanning technique will be used to seek changes in the DNA of the tumours, inparticular loss of genetic material or amplification of regions. Identification of the genetic changes within these tumours should enable better systems of classification, enhance prognostication and provide specific targets for the development of appropriate treatment strategies.Read moreRead less
Kallikrein Proteases Have Key Functional Roles In Peritoneal Invasion And Chemoresistance In Epithelial Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$815,541.00
Summary
Only 30% of ovarian cancer patients with advanced disease survive for 5 years. This is because the cancer quickly spreads into the abdominal cavity and often becomes resistant to chemotherapy. We aim to use a new 3D culture system, mouse models and novel inhibitors to study the roles of 4 kallikrein enzymes in these events. The outcomes from this study will lead to a better understanding of the role of kallikreins in ovarian cancer and may lead to new treatment approaches.
Evaluation Of The Therapeutic Potential Of SFTI-FCQR, A Novel Kallikrein 4-specific Protease Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$167,303.00
Summary
Prostate and ovarian cancers are on the rise in Australia's ageing population. In previous work, we have studied prostate and ovarian cancer cells that we have engineered to make the protease KLK4. These cells show signs associated with aggressive tumours and in particular may have some of the changes found in cancer cells that spread from their site of origin (metastasize). In this project, we will look at a drug-like molecule that we have designed with the aim of blocking the activity of KLK4.
Expression And Functional Studies On The Novel Ovarian-expressed Serine Protease, Kallikrein 4, In Ovarian Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$410,250.00
Summary
Ovarian cancer is the leading cause of death from gynaecologic malignancies. In Australia, it is the most life-threatening of all gynaecological cancers. The major reason why the death rate has improved little in the last two decades is that ovarian cancer is detected too late and the type of treatment is not very effective. In this research, we are looking at a new protein, called the K4 protein, which belongs to the same family as the PSA enzyme that is used in the PSA test for prostate cancer ....Ovarian cancer is the leading cause of death from gynaecologic malignancies. In Australia, it is the most life-threatening of all gynaecological cancers. The major reason why the death rate has improved little in the last two decades is that ovarian cancer is detected too late and the type of treatment is not very effective. In this research, we are looking at a new protein, called the K4 protein, which belongs to the same family as the PSA enzyme that is used in the PSA test for prostate cancer. Our preliminary findings suggest that K4 is increased in the serous type ovarian cancer tumours so we intend to determine if K4 will be a useful bio-marker for this type of ovarian cancer. We also have made some interesting findings of some novel forms of the K4 protein and gene in ovarian cancer tissues and we intend to characterise these further to see if they might also be useful in detection of this disease. We are also studying the function and localisation of these different forms of K4 in cancer cells, to identify the exact role the enzyme performs in cancer development. These latter studies will help us understand the disease process better and may help us design new treatment approaches.Read moreRead less
The Clinicial Centre Of Research Excellence At The Jean Hailes Foundation: For The Study Of Women's Health
Funder
National Health and Medical Research Council
Funding Amount
$2,000,000.00
Summary
The major health issues affecting women from the mid-reproductive years include depression, disorders of mood and sexual function, and breast cancer, with cardiovascular disease, osteoporosis, and osteoarthritis becoming increasingly prevalent with age. Linking each of these are their known or probable causal associations with oestrogens and androgens. This Centre will provide an opportunity for comprehensive and multidisciplinary research into the role of oestrogens and androgens in these disor ....The major health issues affecting women from the mid-reproductive years include depression, disorders of mood and sexual function, and breast cancer, with cardiovascular disease, osteoporosis, and osteoarthritis becoming increasingly prevalent with age. Linking each of these are their known or probable causal associations with oestrogens and androgens. This Centre will provide an opportunity for comprehensive and multidisciplinary research into the role of oestrogens and androgens in these disorders.Read moreRead less