Predicting Response To Chemoradiotherapy In Patients With Advanced Rectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$461,605.00
Summary
Many cancer patients receive expensive and unpleasant therapies that actually do not benefit them. This project will use a new technology that can simultaneously assess the level of expression of thousands of genes. We will test if the pattern of gene expression in tumours can predict the patients' response to therapy. Success will significantly improve the clinical management of advanced cancer patients and provide a rational basis upon which to tailor individualized treatment regimes.
The Use Of Gene Expression Profiles To Predict The Response To Chemoradiotherapy In Patients With Oesophageal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$384,600.00
Summary
One of the most difficult and clinically important questions facing clinicians treating advanced cancer is deciding which patients will, and who will not, benefit from chemotherapy and-or radiotherapy. This is particularly true for clinicians treating locally advanced oesophageal cancer. Oesophageal cancer is a particularly aggressive tumour with a poor prognosis; the majority of patients die within 1 year of diagnosis with only 10% surviving to 5 years. In an attempt to improve outcomes, the us ....One of the most difficult and clinically important questions facing clinicians treating advanced cancer is deciding which patients will, and who will not, benefit from chemotherapy and-or radiotherapy. This is particularly true for clinicians treating locally advanced oesophageal cancer. Oesophageal cancer is a particularly aggressive tumour with a poor prognosis; the majority of patients die within 1 year of diagnosis with only 10% surviving to 5 years. In an attempt to improve outcomes, the use of preoperative (neoadjuvant) combined chemotherapy and radiotherapy as an adjunct to surgery has become common practice. Neoadjuvant therapy has been reported to induce complete regression of the tumour and increased survival times in 20-30% of patients. However, the lack of any apparent clinical benefit for those patients who are poor or non-responders to chemoradiation implies that a large proportion of patients are being exposed to significant toxicity and potential complication for no obvious advantage. In the project outlined in this application, we propose to use cDNA microarrays, a technology that allows the simultaneous assessment of the level of expression of thousands of genes at once, to profile the gene expression patterns of oesophageal tumours. These profiles will then correlated to the patients response to treatment to determine if the gene expression patterns can be used to predict the clinical response to chemoradiotherapy. Success will open the path to the development of a clinically important test that would significantly improve the management of advanced cancer patients by enabling personalised therapy for individual patients. Not only will this allow the selection of the most effective therapy for each patient but it will also free patients from suffering the nasty side effects of treatments that turn out to be of little benefit.Read moreRead less
Predictors Of The Outcomes For Joint Inflammation And Damage In Recent Onset Rheumatoid Arthritis Patients
Funder
National Health and Medical Research Council
Funding Amount
$255,750.00
Summary
Currently, it is difficult to predict what will happen to an individual patient who presents with newly diagnosed rheumatoid arthritis, either as a result of the natural history of the disease or as a result of drug treatment. It is also difficult to decide which drug treatment to offer a patient and when to decide to change the treatment to obtain a better clinical response. This study will investigate whether it is possible to predict the outcomes for a particular patient with rheumatoid arthr ....Currently, it is difficult to predict what will happen to an individual patient who presents with newly diagnosed rheumatoid arthritis, either as a result of the natural history of the disease or as a result of drug treatment. It is also difficult to decide which drug treatment to offer a patient and when to decide to change the treatment to obtain a better clinical response. This study will investigate whether it is possible to predict the outcomes for a particular patient with rheumatoid arthritis for joint inflammation and joint destruction, based on the findings in the joint lining tissue. This study will also investigate whether it is possible to make decisions on the likely success of drug treatment given to a patient with rheumatoid arthritis based on the initial or subsequent joint lining tissue biopsies. If successful, this study will lead to a greater ability to advise patients about likely outcomes from their condition, either with or without treatment and also to predict whether a treatment is likely to work at an early stage. In addition, this study may identify future potential treatments for rheumatoid arthritis.Read moreRead less
The outcomes to be assessed are recurrent ischaemic stroke, intracranial haemorrhage, myocardial infarction, parenchymal embolism and vascular death. Should these outcomes be significantly reduced, the public health and economic issues which will be addressed in this study are considerable. Approximately 40,000 new and recurrent cases of stroke occur in Australia each year, and about 80% of these are ischaemic. There is an average prevalence of about 20% of large or complex aortic plaque among p ....The outcomes to be assessed are recurrent ischaemic stroke, intracranial haemorrhage, myocardial infarction, parenchymal embolism and vascular death. Should these outcomes be significantly reduced, the public health and economic issues which will be addressed in this study are considerable. Approximately 40,000 new and recurrent cases of stroke occur in Australia each year, and about 80% of these are ischaemic. There is an average prevalence of about 20% of large or complex aortic plaque among patients with ischaemic stroke. About the same proportion of cases of ischaemic stroke yearly are associated with the presence of complex aortic plaque alone, and as many again with simple plaque (40% in total). Using the NHMRC estimated cost of $40,000 per stroke (and assuming that recurrent stroke costs are similar to initial stroke costs) and the estimated recurrent stroke rates of 11.9-100 person-years for plaque > 4 mm, the national cost of recurrent ischaemic stroke attributable to complex aortic plaque alone is about $3 million in the first year. This estimate does not include patients with incident TIA and atherosclerotic plaque or the resources spent on evaluating recurrent stroke and TIA attributable to aortic plaque, the cost of lost wages, or the negative impact on the quality of life of the victims. The economic and public health burden to our society could be greatly reduced by successful efforts at secondary stroke prevention in individuals with aortic plaque and TIA or ischaemic stroke. If just 25% of recurrent ischaemic strokes associated with aortic arch debris could be prevented by treatment interventions, the annual savings to society for recurrent ischaemic stroke alone would be considerable.Read moreRead less
A Case Control Study Investigating Factors Contributing To The Risk Of Bleeding In Patients Receiving Warfarin Therapy
Funder
National Health and Medical Research Council
Funding Amount
$572,242.00
Summary
Warfarin is a drug commonly used in the elderly to prevent blood clots. Blood clots can lead to stroke. While a very effective drug, it is also a dangerous drug because it can lead to thin blood which makes it more likely that they will bleed. For this reason, the drug should be closely monitored. We know that many people do suffer catastrophic bleeds because the blood is too thin directly as a result of taking warfarin. Some of the reasons for these bleeds are well known; they may be taking dru ....Warfarin is a drug commonly used in the elderly to prevent blood clots. Blood clots can lead to stroke. While a very effective drug, it is also a dangerous drug because it can lead to thin blood which makes it more likely that they will bleed. For this reason, the drug should be closely monitored. We know that many people do suffer catastrophic bleeds because the blood is too thin directly as a result of taking warfarin. Some of the reasons for these bleeds are well known; they may be taking drugs that interact with warfarin, they may have problems with their liver or kidney which affects the body's ability to get rid of it, they may have suffered a fall, to name a few. Studies done overseas have suggested that people are more likely to have a bleed if they do not know how to properly manage their tablets, if they are depressed, if they have no helpers to support them or if their care is not well organised. In Australia, we do not know what impact the organisation of care has on whether a person's warfarin is well managed. We do not know the impact that depression has on their care, or whether people are more likely to have pooorly controlled warfarin if they have few community ties. These are importnat questions to answer, so that we can make significant inroads into preventing death and disability from warfarin.Read moreRead less
Targeting Antimicrobial Resistance And Host Immune Evasion In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$892,831.00
Summary
This project aims to show how one of the most important human superbugs, Staphylococcus aureus (Golden staph), develops resistance to one of our most important last-line antibiotics and the immune system to cause life-threatening infections. Our work will also investigate and test new treatment strategies for this common and challenging human pathogen.
Long-term Human Response Following Subretinal Injection Of Recombinant Adenoassociated Virus-sFlt-1 Vector
Funder
National Health and Medical Research Council
Funding Amount
$373,076.00
Summary
Age-related Macular Degeneration (AMD) is the major cause of blindness in the developed world. The present best practice for treating wet AMD is monthly injections of Lucentis� into the eye which is expensive, inconvenient for the patient and has increased risk of infection. The additional assays associated with the clinical trial will test whether adeno-associated virus-mediated gene therapy is safe and whether it can eliminate the need of multiple injections while delivering the same outcome.
Insult, Injury And Recovery In Brain Disease: From Molecules To Therapeutic Outcome
Funder
National Health and Medical Research Council
Funding Amount
$8,215,611.00
Summary
When nerve cells are damaged, destroyed or injured, through disease or trauma, common pathological processes are set in train. Even though there are many factors that might trigger disease, these inevitably lead to common processes that end in cell death or initiate protective processes. One theme involves the factors that surround these responses to nerve injury and stress, and the consequent protective and regenerative responses that ensue. Another theme, closely integrates with the first, is ....When nerve cells are damaged, destroyed or injured, through disease or trauma, common pathological processes are set in train. Even though there are many factors that might trigger disease, these inevitably lead to common processes that end in cell death or initiate protective processes. One theme involves the factors that surround these responses to nerve injury and stress, and the consequent protective and regenerative responses that ensue. Another theme, closely integrates with the first, is to exploit basic biological mechanisms with the aim of identifying and developing therapeutic targets for the management of a wider range of neurological conditions.Read moreRead less
DETECTION OF OCCULT DISSEMINATED TUMOUR CELLS AND TUMOUR DNA IN EARLY STAGE OPERABLE BREAST CANCER PATIENTS
Funder
National Health and Medical Research Council
Funding Amount
$561,000.00
Summary
Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant ....Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant risk of under treating good prognosis disease patients (20%) and over treating women with intermediate and high risk disease (40%). The first aim of the study is to use novel molecular methodologies to detect breast cancer cells in the blood of patients with early stage breast cancer at diagnosis. The presence of tumour cells will be correlated with the usual prognostic factors used in the management of women with breast cancer. The patients will be followed long-term to clarify the relationship between disseminated tumour cells in the blood and bone marrow and eventual outcome to assess the effectiveness of these new methodologies in patient management. We will also assess new molecular methodologies which will allow us to track very low levels of disease, and thereby monitor the effectiveness of treatment, and allow prediction of impending relapse. Studying the blood of breast cancer patients represents a unique opportunity for determining whether the cancer has spread before surgery and for monitoring of disease after surgical removal of the tumour. This study may prove invaluable in predicting disease free and survival outcomes and provide a more rational approach to the use of chemotherapy in patients with early breast cancer.Read moreRead less