OVARIAN CANCER METASTASIS: Unraveling The Biology Of The Plasminogen Activation Cascade
Funder
National Health and Medical Research Council
Funding Amount
$169,875.00
Summary
Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of t ....Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of the biology of ovarian cancer metastasis may lead to new therapies designed to control these processes - as such this would be a major inroad into our fight against this cancer. The aim of this novel research project is to unravel the role that one cell surface system (the plasminogen (Plg) activation cascade) plays in determining the ability of ovarian cancer cells to metastasise and regulate new tumour blood vessel formation. This study addresses the paradoxical observations that this cascade can simultaneously facilitate cancer metastasis whilst concomitantly stopping new blood vessel formation in tumours. Using a number of advanced molecular cell biology methods, the hypothesis we will test is that the capacity of ovarian cancer to metastasise is determined by differential processing of plasminogen subsequent to cell-surface Plg binding. This results in a delicate balance between the generation of cell surface proteases and the release of protein fragments capable of stopping tumour blood vessel growth. Our group is well-equipped to address this hypothesis since we have already shown that: (1) Plg binding and activation is required for cancer cell invasion; (2) Plg binding and activation is elevated on malignant compared to benign cancers (3) Plg unfolds after it binds to cell surfaces or recombinant receptors; and, (4) Plg is easily fragmented to products that inhibit new blood vessel formation after binding to some cancer cells.Read moreRead less
New Approaches To Improve Thrombolysis In Ischaemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Ischaemic stroke is caused by the presence of a blood clot in the brain. The removal of these clots is achieved using an enzyme called tissue-type plasminogen activator (t-PA). While this agent is effective if given to patients within 4.5h of stroke onset, delayed administration can cause cerebral bleeding. This project is to understand how t-PA promotes these unwanted effects in the brain and to devise novel approaches to extend the time window of t-PA administration in these patients.
A Novel Non-invasive Diagnostic Imaging Technique Of Metastatic Cancer Using Plasminogen Activator Inhibitor Type 2.
Funder
National Health and Medical Research Council
Funding Amount
$187,750.00
Summary
This project aims to develop a non-invasive tumour diagnostic imaging agent based on a non-toxic protein (PAI2) that we know specifically identifies a critical marker of malignancy. PAI2 will be labelled with commonly used imaging radioisotopes. This novel imaging technique has important potential clinical uses including, determination of the most appropriate treatment for individual patients, assessing the success of such treatments, and a novel non-invasive prognostic indicator of malignancy.
Plasmin is a complex enzyme that performs major roles in removal of blood clots, wound healing and in tumor metastasis. Here we will understand how plasmin function is regulated at the molecular level. These key insights will be of future use in the development of therapeutics targeting the plasmin system in cancer and clotting diseases.
Defining The Mechanism Of Invasive Disease Caused By Diverse Group A Streptococcal M Serotypes
Funder
National Health and Medical Research Council
Funding Amount
$393,061.00
Summary
Streptococcus pyogenes (group A Streptococcus; GAS) causes life-threatening invasive infections including flesh-eating disease and toxic shock syndrome (>600,000 cases and 163,000 deaths per year). We recently discovered the trigger for invasive disease in a globally disseminated GAS strain. The aim of this work is to determine whether this trigger applies to other strains associated with GAS invasive disease. These studies will allow the development of new therapeutics and treatments.
Environmentally Benign Flotation Chemicals. The research described in this proposal and the anticipated outcomes are concerned with replacing toxic and environmentally hazardous chemicals used in the mineral processing industry with benign chemicals that are biodegradable and have low toxicity. Replacing these chemicals reduces the risk of workplace injuries and damage to the environment that could be caused by industrial accidents.