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.
Cellular Responses To Thrombin In Skeletal Pathology
Funder
National Health and Medical Research Council
Funding Amount
$120,775.00
Summary
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also causes bone cells to alter their behaviour. Thrombin stimulates proliferation of bone-forming cells and protects them from premature death. Thrombin also stimulates t ....Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also causes bone cells to alter their behaviour. Thrombin stimulates proliferation of bone-forming cells and protects them from premature death. Thrombin also stimulates the breakdown of bone. We will investigate how thrombin's effects on bone cell behaviour influence the course of bone healing. We will also determine how thrombin stimulates bone breakdown and increases survival of bone-forming cells. This study will contribute to the understanding of how bone cells function in health and disease.Read moreRead less
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.
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
The Role Of Protease-activated Receptor-2 In Regulation Of Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$216,100.00
Summary
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. We have recently demonstrated the presence of a receptor called PAR-2 on bone-forming cells. We have also shown that activation of PAR-2 inhibits the development of bone-resorbing cells (osteoclasts) in response to hormones. We ....Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. We have recently demonstrated the presence of a receptor called PAR-2 on bone-forming cells. We have also shown that activation of PAR-2 inhibits the development of bone-resorbing cells (osteoclasts) in response to hormones. We plan to investigate the mechanism of this effect, as well as to identify how PAR-2 activation modulates other responses of bone cells to hormones. Molecules that activate PAR-2 are present in bone in certain disease situations, but it is not known what activates PAR-2 in bone under normal conditions. We will identify physiological activators of PAR-2 within bone.Read moreRead less