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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
Infrared Spectroscopic Imaging In The Diagnosis Of Cervical Cancer
Funder
National Health and Medical Research Council
Funding Amount
$291,600.00
Summary
In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to pro ....In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to probe smears shows promise in providing such an easily automated reliable method. We, and others have spent a number of years exploring this technique and have solved a number of the problems associated with it. Based on our work in the field and the work of others we now wish to develop a methodology using an infrared micro-imaging spectrometer combined with multivariate statistics that can be used to diagnose cervical cancer and the conditions that lead to cervical cancer.Read moreRead less
The Effect Of Asthma During Pregnancy On Placental Function And Fetal Development
Funder
National Health and Medical Research Council
Funding Amount
$378,600.00
Summary
Asthma affects 12% of the Australian population and is expected to increase to 20% over the next 10 years. This rise will result in an increase in the number of women who suffer from asthma during pregnancy and could emerge as a major public health problem since asthma during pregnancy is associated with low birthweight babies. Lower birthweight itself is an increased risk factor for a number of adult diseases such as diabetes and coronary artery disease and thus the children of asthmatic women ....Asthma affects 12% of the Australian population and is expected to increase to 20% over the next 10 years. This rise will result in an increase in the number of women who suffer from asthma during pregnancy and could emerge as a major public health problem since asthma during pregnancy is associated with low birthweight babies. Lower birthweight itself is an increased risk factor for a number of adult diseases such as diabetes and coronary artery disease and thus the children of asthmatic women are at risk for numerous pathologies throughout life. Nevertheless, the specific mechanisms that cause low birthweight in asthmatic pregnancies are unknown. We currently have a lead in this important area. Our data so far indicates that asthma produces alterations in placental blood flow and glucocorticoid metabolism that are particularly pronounced when the fetus is female. Inhaled glucocorticoid therapy is protective of the effects of asthma on the fetus suggesting the involvement of inflammatory pathways. The long term objectives of our work are to elucidate the effects of asthma on fetal health and to design better ways to manage asthma during pregnancy to improve the outcome for the baby. The short term objective of this grant is to define whether inflammatory factors associated with asthma during pregnancy change placental function to adversely affect fetal development and whether these effects are related to the sex of the fetus. Completion of these studies will provide both scientific and clincial outcomes. Scientifically, a biological basis for understanding alterations in placental physiology observed in women with asthma will be produced. Clinically our work will open avenues to optimize therapy for this group of women to improve their pregnancy and the outcome for their babies.Read moreRead less
Fetal Intrapartum Pulse Oximetry: A Multicentre Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$246,001.00
Summary
Current methods of monitoring the well-being of the unborn baby during labour often result in concern about the unborn baby's health. This leads to delivery by caesarean section, forceps, or vacuum. These babies are usually found to be healthy once born, meaning that the operation was unnecessary. In this study, when an unborn baby appears to be distressed, half of the study participants will be allocated to continue with the current monitoring of the baby's heartbeat. The other half will have a ....Current methods of monitoring the well-being of the unborn baby during labour often result in concern about the unborn baby's health. This leads to delivery by caesarean section, forceps, or vacuum. These babies are usually found to be healthy once born, meaning that the operation was unnecessary. In this study, when an unborn baby appears to be distressed, half of the study participants will be allocated to continue with the current monitoring of the baby's heartbeat. The other half will have a new form of monitoring in labour, fetal oxygen saturation monitoring, added. We will then determine whether the new form of monitoring makes a difference in the number of times women need to have a caesarean section, forceps, or vacuum delivery. It is important to do this research BEFORE the new form of monitoring becomes used routinely. This Australian research is leading the world in letting the health consumer (women) know whether the now monitoring method is effective in practice and ensuring that there are no unforeseen adverse events.Read moreRead less
A Media Formulation To Improve Implantation Rates And Pregnancy Outcome Following ART
Funder
National Health and Medical Research Council
Funding Amount
$304,380.00
Summary
Since women are delaying childbearing, ART is increasingly required. 2-3% of births in Australia follow ART. Only 15-40% of embryo transfers in assisted reproduction (ART) result in ongoing pregnancies. The poor success rate is due to the fact that the embryo culture media bear no resemblance to the maternal environment in which they grow normally. The new culture media to be validated in this proposal includes factors that are critical for embryo implantation and will improve ART success.
Limiting Weight Gain In Overweight And Obese Women During Pregnancy To Improve Health Outcomes - A Randomised Trial.
Funder
National Health and Medical Research Council
Funding Amount
$1,541,444.00
Summary
Being overweight or obese is a major health issue for women during pregnancy and childbirth in Australia. There are well documented risks associated with obesity during pregnancy for both the mother and her baby. This randomised trial will assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese pregnancy women to limit weight gain during pregnancy is effective in improving health outcomes for women and their babies.
Improving Birth Outcomes in China: consequences and potentials of policy, state and professional interactions. The aim of the project is to reduce morbidity and mortality associated with birth by informing health systems improvement in China. We will develop an innovative methodology to study consequences of policy, state and professional interactions on birth outcomes. This work is also relevant in other settings. Macro economic reforms in China have produced paradoxical disparities between ri ....Improving Birth Outcomes in China: consequences and potentials of policy, state and professional interactions. The aim of the project is to reduce morbidity and mortality associated with birth by informing health systems improvement in China. We will develop an innovative methodology to study consequences of policy, state and professional interactions on birth outcomes. This work is also relevant in other settings. Macro economic reforms in China have produced paradoxical disparities between rich and poor and urban and rural populations evident in maternal morbidity and mortality. Results will inform facilitative policies and models of service to optimise safety and increase effectiveness in deployment of human and monetary resources.Read moreRead less