CHARACTERISATION OF THE PROSTATE ANDROGEN-RESPONSE PROGRAM USING COMBINED TRANSCRIPT AND PROTEIN EXPRESSION PROFILING
Funder
National Health and Medical Research Council
Funding Amount
$232,200.00
Summary
Carcinoma of the prostate exhibits a wide range of biological variation influenced by genetic, racial, environmental, and other as yet undefined factors. For 1997 the Australian Bureau of Statistics estimates revealed that 27% of all deaths (> 34,000) were due to cancer. Among males, the second leading cause of death (13%) was prostate cancer. The development and progression of human prostate cancer is driven by the accumulation of genetic changes and influenced by a multitude of currently un ....Carcinoma of the prostate exhibits a wide range of biological variation influenced by genetic, racial, environmental, and other as yet undefined factors. For 1997 the Australian Bureau of Statistics estimates revealed that 27% of all deaths (> 34,000) were due to cancer. Among males, the second leading cause of death (13%) was prostate cancer. The development and progression of human prostate cancer is driven by the accumulation of genetic changes and influenced by a multitude of currently unknown events. In addition, a genetic predisposition to certain environmental elements may also provide susceptibility to the onset of prostate cancer. Inherent in identifying the mechanisms leading to prostate cancer is defining the molecular factors involved in the biological processes that influence the development, progression, and treatment of this malignancy. This proposal aims to address the lack of fundamental knowledge relating to the androgen hormone mediated molecular pathways through a comprehensive approach using genomic (DNA), transcribed (RNA) and translated (protein) information that will define the components of the androgen regulated events; i.e. identify the proteins and genes directly or indirectly regulated by androgenic hormones and their cognate receptors. Importantly we will apply technologies that can detect molecular changes in the cell without preconceived ideas about which information will be most valuable to monitor or which technologies will have the greatest impact. We anticipate that the characterisation of the prostate androgen-response will not only provide fundamental knowledge concerning androgen-mediated mechanisms of growth and cellular differentiation, but will also provide a molecular framework for therapeutic intervention through the identification of novel therapeutic targets suitable for a variety of interventions ranging from dietary modification to immunological and gene-therapy approaches.Read moreRead less
The Cause Of Undescended Testis And Inguinal Hernia
Funder
National Health and Medical Research Council
Funding Amount
$743,848.00
Summary
This study aims to define in both animal models and children how the testis descends from the abdomen to scrotum, and how undescended testis and inguinal hernia are likely to be caused by defects in the same, very indirect signalling pathway. The results will demonstrate where to look for genetic causes and proof of principle for possible future medical treatments for the 3 commonest major operations in children for congenital and acquired undescended testis and inguinal hernia.
Role Of Pacemaker Cells In The Generation Of Slow Wave Activity In The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$231,500.00
Summary
The prostate gland commonly enlarges in ageing males resulting in a condition known as benign prostatic hyperplasia which is poorly understood. Because of the strategic position of the prostate, its enlargement physically compresses the segment of the urinary system passing through it causing inconvenient and distressing symptoms, such as difficulty and hesitancy in urination, which often require surgical or medical intervention. Indeed patients diagnosed with benign prostatic hyperplasia are of ....The prostate gland commonly enlarges in ageing males resulting in a condition known as benign prostatic hyperplasia which is poorly understood. Because of the strategic position of the prostate, its enlargement physically compresses the segment of the urinary system passing through it causing inconvenient and distressing symptoms, such as difficulty and hesitancy in urination, which often require surgical or medical intervention. Indeed patients diagnosed with benign prostatic hyperplasia are often treated with pharmacological agents that reduce the size of the prostate or relax the prostate and bladder, thus relieving some of the symptoms. However, the precise cellualr mechanisms by which many of these drugs mediate their effects have not been confirmed. Moreover, although previous studies of the prostate gland have clearly established many of the basic properties of the tissue, there is currently a lack of information regarding the prostate gland at a cellular level. We have recently identified a specialised group of 'interstitial cells' in the prostate gland, which resemble the well-described 'interstitial cells of Cajal' in the gut. In the gut, these cells perform a wide variety of functions including the initiation of contractile activity. Interstitial cells are also thought to play a role in diseases of the bowel. This project aims to investigate the role of the interstitial cells in the functioning of the prostate gland. In addition, the effects of age and hormones on the interstitial cells will be considered, which may lead to a better understanding of conditions such as benign prostatic hyperplasia. Finally, identifying nerve-released substances that may affect the activity of these cells may also help identify alternative targets for treatment of benign prostatic hyperplasia.Read moreRead less
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.
Investigating Caloric Vestibular Stimulation As A Novel Therapeutic Intervention For Chronic Pain, Mania And Depression.
Funder
National Health and Medical Research Council
Funding Amount
$340,963.00
Summary
Chronic pain, mania and depression are common health problems worldwide and represent an enormous burden of illness. Current treatments may be costly, invasive and have serious side-effects. In the proposed project, demonstration of therapeutic benefit with a novel, simple method of brain stimulation without such limitations could change how these disorders are managed. Moreover, the findings would be of substantial significance in developing countries where treatments are often non-existent.
Characterisation Of Alterations In The Androgen Signalling Axis That Contribute To Treatment Failure In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,157.00
Summary
Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical mean ....Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical means (ie androgen ablation) is the only effective treatment option available. While androgen ablation is initially effective, treatment failure is common, resulting in a very poor overall survival rate. Evidence from our studies and others suggest that, the androgen receptor, which mediates the growth regulatory effects of androgens is often defective in prostate tumour cells. These altered or mutant receptors are activated inappropriately by other sex hormones such as estradiol and even agents used in the treatment of prostate cancer whereas the normal receptor is activated only by testicular androgens. This mechanism may explain why treatment fails in a subset of men with advanced prostate cancer. The major objective of our current studies is to define how these mutant androgen receptors cause treatment failure and facilitate prostate tumour growth. In addition, the current studies will evaluate a novel approach to treatment of prostate cancer which, based upon our preliminary results, has the potential to be effective even if alterations are present in the androgen receptor. The current studies therefore will provide a better understanding of factors controlling the growth of prostate tumours, and develop improved treatment approaches for advanced prostate cancer.Read moreRead less
The Essential Role Of Androgen Receptor Signalling In Prostate Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$714,375.00
Summary
An urgent objective in prostate cancer clinical practice is to better predict disease course at diagnosis and to identify patients likely to develop metastatic (lethal) disease. We aim to identify clinically-relevant genes - gene pathways that are important in prostate cancer development and progression and which can be used to improve prediction of patient outcome. Prostate cancer management can be improved by tailoring treatments for individual patients.