Uptake of fertility preservation procedures (eg. egg and embryo freezing) prior to cancer treatment is increasing and women will return to use these to try to conceive. Radiation may damage the uterus and there is insufficient evidence to guide the management of those exposed to intermediate doses. The aim is to improve understanding of radiation effects on the uterus which will assist clinicians with deciding whether it can support a pregnancy, or if surrogacy should be advised.
Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently require ....Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently required. The sequencing of the human genome and advanced screening technology (microarrays) allow the detailed analysis of expression patterns in large numbers of specimens. We propose to study the genetic features of this disease by investigating 28 childhood ALL patients from whom we have stored specimens received at two time points, one at diagnosis and one at relapse. The hypothesis of this study is that relapsed leukaemias display genetic features which are correlated to their resistance to therapy. The specific questions we will be asking are: (1) Which genes are expressed at high levels in leukaemia specimens at the time of relapse while not expressed (or expressed at lower levels) at the time of diagnosis and vice versa? (2) What is the function of differentially expressed genes? (3) Is the pattern of gene expression correlated with resistance to the particular drug therapy used? (4) Is the leukaemia clone at relapse related or unrelated to the clone present at diagnosis, as determined by receptor rearrangement? The expression levels of identified discriminator genes will be confirmed by real-time quantitative polymerase chain reaction (PCR). The quality of this set of specimens makes them particularly suited to achieve the stated goals, providing a unique opportunity to investigate drug resistance in childhood ALL. The data generated will provide the basis for the examination of genes suitable as new therapeutic targets.Read moreRead less
Measuring Adverse Events: Development Of A Patient-Centred Adverse Event Reporting Tool (PAET)
Funder
National Health and Medical Research Council
Funding Amount
$454,721.00
Summary
The decision to treat a patient depends on knowing whether the treatment does more good than harm. If it is likely that the treatment will work as well as or better than other treatments and will have minimal associated risks, then that treatment would be recommended unless unavailable or prohibited by cost. Given two equally effective treatments the one with fewer side effects and greater tolerability would be preferred by all. In the process of acquiring knowledge on treatment benefit and trea ....The decision to treat a patient depends on knowing whether the treatment does more good than harm. If it is likely that the treatment will work as well as or better than other treatments and will have minimal associated risks, then that treatment would be recommended unless unavailable or prohibited by cost. Given two equally effective treatments the one with fewer side effects and greater tolerability would be preferred by all. In the process of acquiring knowledge on treatment benefit and treatment harm we rely on evidence from clinical trials. However, the evaluation of benefit versus harm is not symmetric in this setting. Much more effort (e.g. study design, study power, standardisation of efficacy outcome measures) goes into the assessment of whether a treatment works and rather than its potential harm, as measured by adverse events. Adverse event ascertainment and reporting is poorly standardised . There is no standardised measurement process that elicits adverse event information. There is no standardised method for quantifying adverse event information into an index or profile scores equivalent to instruments developed to measure health status, quality of life and other benefits of treatment. Developing astandardised Patient-centred Adverse Event Questionnaire will benefit multiple stakeholders. For Patients: An easy to understand summary measure of treatment harm aids patient understanding of the benefit versus risk. For Doctors, allied health professionals: The Questionnaire includes drug profiles, to align a drug profile with an individual patient's clinical profile. This leads to better patient care. In health policy: All of the above has flow-on effects for policy. Better adverse event data will facilitate information and understanding generally of risks of treatments, risk-benefits of treatments, and cost-effectiveness of management strategies.Read moreRead less
Overcoming Breast Cancer Heterogeneity And Resistance Using A Novel Therapeutic Approach Targeting The Metastasis Suppressor NDRG1.
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Breast cancer (BrCa) is the leading cause of cancer death in women and current treatments suffer from development of resistance, leading to metastatic progression. I will assess a novel treatment strategy for BrCa, targeting a gene that is able to inhibit multiple key drivers of BrCa, using a novel potent and selective anti-cancer agent. This approach has the potential to overcome resistance to current therapies and alleviate the onset of metastasis, to improve prognosis for BrCa patients.
TACI: A Novel Immune Checkpoint In Chronic Lymphocytic Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$874,462.00
Summary
Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. CLL cells actively shut down immune defenses in patients. Moreover, current as well as emerging more targeted therapies suppress immunity and over a quarter of patients will die from an infection despite a good response to cancer treatments. Our laboratory has gained new understanding in the mechanism of action of a new treatment for CLL called Ibrutinib. This information allows us to design improved treatment options for CLL.
Age-related Macular Degeneration: A Cause And A Cure
Funder
National Health and Medical Research Council
Funding Amount
$828,300.00
Summary
Age-related macular degeneration (AMD) is a leading cause of vision loss and there is urgent need for an intervention to slow disease progression. AMD is characterised by debris accumulation in the retina and I will investigate if loss of function in cells that should clear this debris is a critical step in the development of AMD. I will trial a novel laser intervention to slow progression of disease and use basic science techniques to investigate the mechanisms of action of the laser.
Outcome Of Childhood Asthma In Adult Life And The Interaction With COPD
Funder
National Health and Medical Research Council
Funding Amount
$503,549.00
Summary
The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approac ....The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approaches to treatment of paediatric asthma nationally and internationally. The results of the study have been published widely over the years and cited extensively. The members of this cohort turn 50 in 2007 and will be invited to participate in a further review to reassess their clinical outcome to examine the relationship between long standing asthma and the development of COPD. Those members of the cohort who have had asthma persisting through their adult years have a degree of fixed obstruction on their tests of lung function and are potentially at risk of developing COPD. Some are at increased risk as approximately 30% of the members are regular smokers. In this review, at age 59 years, there is an excellent opportunity to examine the interaction of asthma and COPD and to compare the inflammatory processes between those who have continuing asthma, those whose asthma has resolved and in each group examine the effect of smoking. We will also look at a numbers of genetic markers associated with COPD to identify those who are more susceptible to the development of COPD. A second area of interest is the components of the immune system that influence asthma.. In an earlier study we identified one component of the immune system, known as the T cell system, that had returned to normal in those whose asthma had resolved. In this review, we plan to examine the T cell system in detail to understand what mechanisms may be responsible for resolution of childhood asthma.Read moreRead less
Patient-reported Outcomes And Treatment Preferences In 1,900 Men With Prostate Cancer Participating In Two International, Randomised Clinical Trials
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Men with high-risk or metastatic prostate cancer are faced with difficult and uncertain trade-offs between quantity and quality of life when making a treatment decision. The proposed study extends two promising, ongoing clinical trials by describing the quality of life outcomes and treatment.