Investigation Of Steroidogenesis As A Mechanism Of Castration Resistance In Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$419,076.00
Summary
Prostate cancer is critically dependent upon continued testosterone stimulation, even when the disease becomes resistant to existing hormonal therapies that suppress serum levels. The source of this testosterone is currently unclear. This study aims to identify the site of testosterone synthesis in patients with prostate cancer, and determine the relevance of continued testosterone signalling in patients treated with 'super castrating' hormonal therapy.
Prognostic Importance Of Androgen Receptors In Epithelium And Stroma In Early Stage Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$348,750.00
Summary
The use of serum prostate specific antigen (PSA) to screen asymptomatic men for prostate cancer has reduced the stage of disease at diagnosis. The majority of tumours are now small and potentially organ-confined. The use of nomograms, algorithms based on preoperative clinical features of these patients (serum PSA level, Gleason grade, clinical stage) has facilitated this process, but is imperfect as 20-30% of patients experience disease relapse within 5-7 years. Tumours with similar preoperative ....The use of serum prostate specific antigen (PSA) to screen asymptomatic men for prostate cancer has reduced the stage of disease at diagnosis. The majority of tumours are now small and potentially organ-confined. The use of nomograms, algorithms based on preoperative clinical features of these patients (serum PSA level, Gleason grade, clinical stage) has facilitated this process, but is imperfect as 20-30% of patients experience disease relapse within 5-7 years. Tumours with similar preoperative clinical features have markedly different outcomes, reinforcing the inadequacy of current approaches to determining whether or not an individual patient has organ-confined disease. A new approach is to incorporate into the standard diagnostic nomograms, biological features from preoperative core biopsy linked to the process of disease relapse, and which independently predict patient outcome risk group. Our preliminary studies using a small hypothesis-generating cohort of patients with early stage prostate cancer determined that elevated levels of androgen receptors (AR) in malignant epithelial cells and reduced levels of AR in peritumoral stromal cells independently predict disease relapse after surgery. In this project, AR measurements will be analysed in independent cohorts of patients derived from two Australian institutions to determine whether the predictive value is maintained across multi-Institutional cohorts. Selected androgen-regulated markers of tumour growth and spread (proliferative, apoptotic, metastatic) will be examined in microarrayed postoperative tissue samples. The postoperative markers will be examined for independence of prediction of relapse. Independent markers will be examined for ability to increase predictive efficacy in standard diagnostic nomograms. Levels of the two markers with greatest predictive value will be measured in preoperative core biopsies and tested for predictive ability as a prelude to clinical practice.Read moreRead less
Defining The Central Role Of Podocyte Depletion In The Development, Progression And Management Of Glomerular Disease
Funder
National Health and Medical Research Council
Funding Amount
$690,855.00
Summary
Podocytes are key cellular components of the kidney’s filtration barrier. Podocyte depletion (cell loss or injury) is a key event in most forms of kidney disease. We will investigate interactions between podocyte depletion and two major risk factors for kidney disease (diabetes and hypertension), assess whether podocyte depletion influences therapeutic outcomes, and commence efforts to develop podocyte-specific therapies.
Generating Endogenous Antigen Specific T Regulatory Cells To Treat Autoimmune MPO-ANCA GN
Funder
National Health and Medical Research Council
Funding Amount
$885,566.00
Summary
Glomerulonephritis (GN) is an inflammatory disease that affects the filtering organs (glomeruli) of the kidney. The most severe and aggressive form is ANCA-associated GN resulting from loss of tolerance to myeloperoxidase (MPO). Current therapies are toxic. This study will develop new strategies to restore immune tolerance to MPO thus treating patients with this disease. We will use an animal model to provide proof-of-concept that these novel therapies can treat MPO-ANCA associated GN.
Cardiovascular Disease; Priorities And Outcomes For People With Chronic And End Stage Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$81,976.00
Summary
This thesis will investigate the patterns, causes and effects of heart disease in chronic kidney disease patients; how heart disease impacts on hospital admission patterns and mortality over time. We will explore the relationship between cognition, cardiovascular and kidney disease; the impact on patient outcomes and quality of life. Finally, we will explore how current research funding reflects disease burden, research output and the stated priorities of patients with chronic kidney disease.
Implementing Innovative Trial Methodologies For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Chronic kidney disease and diabetes are associated with increased cardiovascular disease, hospitalisation and mortality. Health can be improved through better delivery of care. I plan to perform a population based study to identify people with kidney disease or diabetes who do are not receiving optimal care as described in current guidelines. From this, I plan to develop a trial to close the gap. I also plan to assess whether data linkage is an accurate method to conduct trial follow-up.
The SHARP-ER Study: Extended Follow-up Of The SHARP Study Cohort
Funder
National Health and Medical Research Council
Funding Amount
$1,106,265.00
Summary
The SHARP study, conducted from 2003 to 2010, recruited over 9,000 participants with kidney disease and showed, for the first time, that cholesterol-lowering was effective in preventing heart and vascular disease in people with advanced kidney disease. This study will extend follow-up to answers critical questions regarding long-term cardiovascular, renal and other health outcomes.
Growing The Evidence Base For Improved Outcomes In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
One in eight Australians has kidney disease, and is at increased risk of kidney failure, heart disease and stroke, and premature death. Despite this, very few treatments have been proven to be be effective at improving these outcomes. Professor Perkovic will undertake a suite of high-quality randomised trials and systematic reviews that will reliably identify new treatment approaches that will result in better quality and quantity of life for the millions of Australians affected by kidney diseas ....One in eight Australians has kidney disease, and is at increased risk of kidney failure, heart disease and stroke, and premature death. Despite this, very few treatments have been proven to be be effective at improving these outcomes. Professor Perkovic will undertake a suite of high-quality randomised trials and systematic reviews that will reliably identify new treatment approaches that will result in better quality and quantity of life for the millions of Australians affected by kidney diseaseRead moreRead less