Proteolytic And Non-proteolytic Roles For PSA And Related Kallikrein Serine Proteases In Prostate Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$480,128.00
Summary
Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the pri ....Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the primary tumour and out of the prostate, it is possible that high production of these kallikrein enzymes by prosttae cancer cells may increase the ability of these cells to metastasise. In previous work, we have studied prostate cancer cells that we have engineered to make the kallikreins, PSA and kallikrein 4. Those cells that make PSA or kallikrein 4 are more elongated in shape and are better able to move across a porous barrier. Another important change is that these cells stop producing a protein that is usually found on the surface of these cells and is important for helping cells to stay attached to each other. When this protein is lost, these tumour cells no longer stay attached to each other and are more likely to move out of the prostate and spread into other parts of the body. The changes we observed in the cells that produce PSA and kallikrein 4 are typical of these more aggressive cancer cells. In this project, we will look at how PSA and kallikrein 4 cause the cells to undergo these changes. The majority of prostate cancer deaths arise from cancer that has spread from the primary tumour and out of the prostate capsule. This project aims to further understand the causes of prostate cancer spread and metastasis. This is a vital research priority if we are to address the mortality associated with prostate cancer metastasis and may lead to new treatment approaches for advanced metastic prostate cancer.Read moreRead less
The Role Of A Protease Activated Receptor System In Prostate Cancer Bone Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$582,204.00
Summary
Prostate cancer is one of the most significant health issues for men. This disease occurs because certain proteins start to function abnormally. Our focus is on a protein called PAR2, present on the surface of prostate cancer cells and bone cells, which we propose helps cancer cells to spread to bone. In our project, we aim to understand how this happens so that we can develop ways to block prostate cancer metastasis to bone.
Characterisation Of A Novel Prostate-expressed Kallikrein-like Protease And Its Target Proteins
Funder
National Health and Medical Research Council
Funding Amount
$724,544.00
Summary
Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones o ....Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones or androgens are known to play an important role. Prostate specific antigen or PSA has become widely accepted as a useful tool in helping to detect prostate cancer and then monitoring the disease. PSA, which is regulated by androgens, is an enzyme that either activates or breaks down many proteins that are important in both the normal function of the prostate and in the development of cancer. PSA belongs to a family of enzymes called the kallikreins. We have recently discovered a new member of this family that, like PSA, is also found in the prostate. We have called this new enzyme, K6, as it is the sixth member of this family to be identified. So , this project is about characterising this new K6 enzyme, finding out if it is also found in the prostates of men with BPH and prostate cancer, whether it is also regulated by androgens and what sort of proteins it may activate in these diseases. We will also compare these findings with what we know about PSA in these diseases. From these studies, we will not only understand more about this K6 enzyme and how it might be important in the prostate but also how it relates to PSA. These findings may ultimately lead to some new approaches in the detection and treatment for BPH and prostate cancer.Read moreRead less
Predicting The Individual Risk Of Prostate Cancer In Australian Men
Funder
National Health and Medical Research Council
Funding Amount
$348,656.00
Summary
Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently a ....Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently available for prostate cancer. We will apply standard statistical methods to existing data from the Australian Risk Factors for Prostate Cancer study and from the Australian Institute of Health and Welfare to develop a prostate cancer risk prediction model. We will test how factor like age, detailed family history, diet, baldness status and possibly previous PSA tests and prostate biopsies predict the risk. After developing the model, we will test the accuracy of the predictions in three ways. First, using existing data from the Australian Prostate Cancer Family Study, we will see whether the number of cases in a group of men is close to the number predicted by the model (calibration). Second, to test whether the model discriminate well men who develop prostate cancer from those who do not, we will collect family trees in a sample from the Melbourne Collaborative Cohort Study. We will use these data also to estimate the optimal cut point: men above this level of risk will be considered at high risk. Third, we will apply the model to existing data from the Dutch Prostate Cancer Family Study (DPCFS) to test whether the optimal cut point identify high-risk men and to validate the model in a non-Australian population. Finally, we will prepare a computer package that health professionals will use as decision-making tool in different scenarios including individual cancer risk assessment, design of prevention trials and targeting prevention programs to high-risk men.Read moreRead less
Economic Evaluation And Optimisation Of Services For The Preoperative Assessment And Management Of High Risk Surgical Patients
Funder
National Health and Medical Research Council
Funding Amount
$399,406.00
Summary
Medical co-morbidities in surgical patients affect post-surgical recovery, resulting in higher health service costs and poorer patient outcomes. Preliminary data indicate reduced post-surgical length of stay for patients with modifiable risk factors who attended a specialist preoperative clinic. This project will analyse existing data to identify patient sub-groups with the greatest capacity to benefit from specialist preoperative assessment, and evaluate new service pathways for these patients.