Role Of The Tissue Kallikrein-kinin System In Abdominal Aortic Aneurysm Formation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$457,779.00
Summary
Up to 5% of people over 60 years develop weakening of their aorta leading to slow dilation of the vessel, which may burst resulting in sudden death. The only treatment is surgery, which has complications and is unsuitable for some patients. Drugs which slow the disease would be invaluable. We have identified a role for kinins in aneurysms. We will investigate how these molecules contribute to aortic disease and if blocking them can be used as a basis for medical treatment of artery weakening.
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.
Delayed Phase Of Remote Ischemic Preconditioning: Clinical Application And The Role Of Kallikrein-kinin Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$159,197.00
Summary
Brief episodes of interruption of blood flow to the arm or leg provide strong protection against prolonged interruption of blood flow to a target organ (e.g., heart or lung). This is known as remote ischemic preconditioning (RIPC). The strongest protection occurs 24 hours after blood flow interruption to the limb and may be mediated by a humoral cascade known as kallikrein-kinin. RIPC may provide protection against heart attack and stroke.
Aliskiren: Cardioprotection By Increased Bradykinin Levels?
Funder
National Health and Medical Research Council
Funding Amount
$295,236.00
Summary
Aliskiren is a new treatment for hypertension. Our recent studies indicate that aliskiren may have additional benefits for patients with ischaemic heart disease and heart failure. This research project will investigate the effects of aliskiren in different forms of heart disease in rats, in order to provide information that will help patients obtain the maximum benefit from this treatment.
Kallikrein Gene Variants In Prostate Cancer: Analysis Of Gene Regulation And Diagnostic/Prognostic Use
Funder
National Health and Medical Research Council
Funding Amount
$486,801.00
Summary
Prostate cancer is the most common male cancer in Australia. However, early detection through screening programs has proven challenging, and about 30% of the 10,000 new cases diagnosed annually already have advanced disease. Hence, there is a fundamental need for increased basic research in prostate cancer etiology (cause) and tumour biology, and a critical requirement for methods that will assist in earlier detection of the disease and predict progression. A family of proteins called kallikrein ....Prostate cancer is the most common male cancer in Australia. However, early detection through screening programs has proven challenging, and about 30% of the 10,000 new cases diagnosed annually already have advanced disease. Hence, there is a fundamental need for increased basic research in prostate cancer etiology (cause) and tumour biology, and a critical requirement for methods that will assist in earlier detection of the disease and predict progression. A family of proteins called kallikreins (including prostate specific antigen, PSA) are often associated with clinical features of prostate cancer. We will characterise genetic variants (polymorphisms) in kallikrein genes that are consistently over-produced in prostate cancer, and determine whether they cause more protein to be produced in cells grown in the laboratory and in tumour tissue, and-or give rise to different expression products or splice variants. We will use bioinformatics (computer programs) to characterise published kallikrein gene sequences and to examine them for genetic variants that might be related to changes in gene expression or to splice variants. We will then use a case-control study, involving 1200 men with prostate cancer and 1200 healthy men, to determine whether these gene variants are associated with an increased risk of prostate cancer or with clinical aspects of the disease. Finally, we will examine the functional significance of the gene variants. This project represents an important and novel combination of molecular biology with the study of clinical disease at the population level, in the relatively new field of molecular epidemiology. It will clarify the role of kallikrein gene variants in prostate cancer risk and progression. The technologies may ultimately prove useful clinically for diagnosis of prostate cancer or for monitoring of treatment and prognosis, and hopefully will assist in clinical decision-making.Read moreRead less
Cardiovascular disease is the leading cause of death in Australia. Aliskiren is the first renin inhibitor-type drug to be approved for clinical use for treatment of hypertension. The aim of this project is to evaluate the effectiveness of aliskiren for the treatment of heart attack and heart failure, as compared to existing therapies. Aliskiren may potentially replace or complement current therapies, thereby reducing death and improving health and economic benefits for the community.
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