A Population-based Longitudinal Study Of Cancer Survivors' Psychosocial And Physical Well Being
Funder
National Health and Medical Research Council
Funding Amount
$454,600.00
Summary
Cancer control is a National Health Priority Area. About 345,000 new cases of cancer are diagnosed in Australia each year. It is the second highest cause of death accounting for 27% of all deaths in Australia each year. Improvements in diagnosis and treatment have resulted in a growing number of people living with a history of cancer and for longer periods. Many cancer survivors report experiencing negative effects of cancer such as fatigue, anxiety, depression, and disrupted family and social r ....Cancer control is a National Health Priority Area. About 345,000 new cases of cancer are diagnosed in Australia each year. It is the second highest cause of death accounting for 27% of all deaths in Australia each year. Improvements in diagnosis and treatment have resulted in a growing number of people living with a history of cancer and for longer periods. Many cancer survivors report experiencing negative effects of cancer such as fatigue, anxiety, depression, and disrupted family and social relationships well after treatment has finished. Despite the large burden of this disease, little is known about the later effects that cancer and its treatment has on cancer survivors, their ongoing concerns, how the issues they face change over time and the type of support they need. This will be the first population-based longitudinal survey of the physical and psychosocial effects that cancer has on adult cancer survivors to be undertaken in Australia. It will follow cancer survivors for the first five years from diagnosis to provide data on important outcomes including anxiety, depression, quality of life and unmet needs. It will also provide the first population-based data on the predictors of these outcomes, including social support, coping style and patient demographic, treatment and disease characteristics. Given the large-scale cancer survivorship initiatives underway internationally, it is timely for high quality and comprehensive Australian data to be obtained. These data will provide new information on how the physical, social and emotional impact of cancer changes with time since diagnosis and a better understanding of the support desired by cancer survivors at various stages of recovery or disease progression. This information will help guide the development of policies and services that are tailored to the needs of Australian cancer survivors.Read moreRead less
Linking Of Physiological Models Of Iv Anaesthetic Disposition With Models Of The Cardio- And Cerebro-vascular Systems
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
On average, nearly 1 in 10 Australians are anaesthetised each year. Most cases include an injection of either thiopentone or propofol directly into a vein. These drugs quickly produce the desired loss of consciousness, but can also produce significant undesirable effects on the circulatory system. To date, anaesthetists have relied on their accumulated experience to choose doses of these drugs that achieve an appropriate balance between their desirable and undesirable effects. However, the scien ....On average, nearly 1 in 10 Australians are anaesthetised each year. Most cases include an injection of either thiopentone or propofol directly into a vein. These drugs quickly produce the desired loss of consciousness, but can also produce significant undesirable effects on the circulatory system. To date, anaesthetists have relied on their accumulated experience to choose doses of these drugs that achieve an appropriate balance between their desirable and undesirable effects. However, the scientific basis of this process was poorly understood. Consequently, we conducted experiments in sheep in which we showed that the level of unconsciousness produced by these drugs depended on their concentration in the brain. Each sheep was unharmed and could be studied repeatedly. We established the important factors that influenced this brain concentration, and developed a unique computer model of the processes governing the desirable effects of thiopentone and propofol. However, understanding of what influences the undesirable effects of these drugs is less well developed. In this project, we propose a series of experiments in which we inject the thiopentone and propofol in special sites within the sheep so that we achieve low concentrations in some parts of the body, but high concentrations in others, while also measuring their undesirable effects. This will show which sites in the body high concentrations of drug should be avoided to minimise these undesirable effects. Another series of studies will be used to extend our computer model so that it can predict these undesirable effects. This extended model will allow anaesthetists to visualise and understand the fundamental factors influencing both the desirable and undesirable effects of thiopentone and propofol. This in turn will lead to dose strategies that help the anaesthetist maximise the desirable effects, while minimising the undesirable, in individual patients.Read moreRead less
Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a subst ....Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a substantial group of patients are therefore at risk of an adverse outcome following surgery. Despite the magnitude of this problem, however, few studies have established treatments to decrease the risk of complications and death following surgery. Beta-blockers are a group of drugs which have been used for decades in the treatment of heart disease and high blood pressure. Beta-blockers are known to improve the way the heart copes with the stress of surgery. They decrease the heart rate, make the heart more efficient at using energy and reduce the likelihood of imbalance between oxygen supply and demand. Some previous studies showed that beta-blockers may reduce the risk of heart attack and death for up to 2 years after surgery. However, other studies have shown no effect of beta-blockers on outcome. These previous studies have involved small numbers of patients who may not represent the broader population having surgery. We therefore are undertaking a large trial to definitively answer the question about whether beta-blockers improve the outcome after non-cardiac surgery in patients with, or at risk of, heart disease. Even if the effect of beta-blockers is relatively modest, because such large numbers of patients with heart disease have surgery, the overall effect on the rate of complications and death in the population could be very significant. The results of this study could have major implications for the success of, and cost of, surgery worldwide.Read moreRead less
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Identifying The Targets Of MiRNA Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$290,600.00
Summary
microRNAs are noncoding RNAs with fundamental functions in biology and significant roles disease. microRNAs control gene expression by destroying RNA or controlling its translation into cellular proteins. To determine how certain microRNAs cause human disease it is essential to know their RNA targets. We are developing methods to identify these targets and aim to apply these methods to identify the targets of microRNAs with known roles in cancer.
Polycomb Group Genes In Murine Lymphomagenesisand Their Impact On Drug Response.
Funder
National Health and Medical Research Council
Funding Amount
$476,815.00
Summary
The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes ....The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes are switched on, where, and when. This determines whether a cell behaves normally or whether it may turn into a cancer cell. When Polycomb Group genes themselves are expressed at the wrong time or place, they can cause cancer. In human lymphoma, these genes have been associated with more aggressive lymphoma. This has also been shown for other cancers such as breast and prostate cancer. In some cases these genes are associated with cancers that do worse following anti-cancer treatment. So far, no research has been published looking the direct impact of the Polycomb Group genes on the success of treatment in a controlled laboratory model. We have used a powerful laboratory mouse model of lymphoma, established in the host laboratory, in which over-expression of the c-myc oncogene in developing B cells causes lymphoma. This model is easy to manipulate and this provides us with a great deal of experimental control, much more than can be achieved from working with patient samples. Two family members, Bmi-1 and Cbx7, cause lymphoma to develop aggressively and we will ask whether two other members, Ezh2 and Rybp do this as well. We will determine whether these 4 genes cause drug resistance in lymphoma, with currently used chemotherapy and also with novel anti-cancer drugs. By increasing our understanding of drug resistance in lymphoma, drugs may be utilised more effectively and new markers identified to predict which drug will be successful in treating a particular lymphoma.Read moreRead less
Evaluation Of A Novel Antiosteolytic Agent: Potential In Breast-to-bone Metastasis And Mechanism Of Action
Funder
National Health and Medical Research Council
Funding Amount
$352,583.00
Summary
In breast cancer the spread of cancer (metastasis) to bone occurs frequently and causes significant problems including pain, fracture, immobility and paralysis. We have recently discovered that a drug, widely used in Japan and Korea for skin disorders, inhibits breast cancer growth in bone using animal model systems of this disease. This is a very exciting and novel finding. We will further investigate the potential of this drug and identify precisely how it works at the molecular level.
Proteomic Screening For Apoptotic Markers In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell li ....The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell lines showed time-dependent decreases in two proteins, identified as S100A6 and ubiquitin. Both are known to be important in cell function. In the proposed project we will build on our preliminary findings to provide important new information central to the understanding of cancer cell biology and apoptosis in addition to evaluating the ability of anti-cancer treatments to induce apoptosis. Using a combination of protein analysis technologies, this project has the potential to provide reliable and novel biomarkers which will indicate the efficacy and selectivity of anti-cancer treatments in inducing tumour cell death. The knowledge gained in this project will aid clinical assessment of the response to cancer treatment(s) in patients in the form of specific screening assays, and may result in identification and development of effective new agents for cancer treatment and prevention. Furthermore, the outcomes of this project will increase our understanding of fundamental cancer cell biology and apoptosis.Read moreRead less