The Role Of Microtubule Composition In The Efficacy Of Antimicrotubule Agents In Paediatric Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$173,380.00
Summary
To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggre ....To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggressiveness of certain cancers, and whether this influences which tumours will respond to the vinca alkaloids. The vinca alkaloids are an important class of natural product drugs which disrupt microtubules and are particularly effective in the treatment of adult and childhood cancers. Unfortunately, some cancer cells fail to respond to this treatment due to the development of drug resistance. This proposal addresses vinca alkaloid resistance in children?s cancer and will determine why certain cancer cells fail treatment. Furthermore, this study will identify the role of certain components of microtubules that appear to be related to drug resistance in leukaemia and neuroblastoma cells and whose role is unknown. Chemotherapeutic drugs, such as the vinca alkaloids, are important in the treatment of cancer and knowledge about their interaction with their cellular target will improve the design of new drugs and treatment outcome.Read moreRead less
Transcriptional Regulation Of The Tumour Suppressor Gene, Retinoic Acid Receptor Beta
Funder
National Health and Medical Research Council
Funding Amount
$336,540.00
Summary
Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identif ....Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identified that a particular gene retinoic acid receptor beta, known to be involved in the vitamin A anticancer effect may be deficient in some neuroblastoma tumours, and is vital to the anticancer effect of vitamin A in neuroblastoma cells. In this application we hope to define those cellular factors which are necessary for turning on the expression of this gene.Read moreRead less
Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a c ....Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a cancer prevention strategy. If entirely successful, our experiments will show that the MYCN oncoprotein is a key factor in the very earliest stages of neuroblastoma tumour formation, we will define the mechanism of the MYCN effect on the normal process of neural crest development, and, we will provide a basis for future cancer prevention strategies in children with this disease.Read moreRead less
Understanding The Factors Governing Susceptibility And Outcome In Childhood Infection
Funder
National Health and Medical Research Council
Funding Amount
$276,122.00
Summary
This research seeks to understand why a minority of children are prone to severe and often life-threatening infections and inflammation. It focusses on infections both in preterm infants and in later childhood, which may also be relevant to understanding atherosclerosis. I am also interested in improving the health of recently arrived refugees, by conducting research that allows the development of evidence-based health interventions and developing national policy on refugee health.
In Vitro And In Vivo Assessment Of The Funhaler -an Innovative Therapeutic Device For Children
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler ....Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler incorporates a spinning toy attached to the outside of the spacer. The toy is activated when the patient breathes through the spacer. The device has been designed to encourage children to co-operate when their asthma therapy is being delivered. The Funhaler is currently in the late development stage. We propose, firstly, to carry out in vitro assessments of drug delivery from the Funhaler compared to the two most widely available small volume spacers: the Aerochamber Plus (Trudell, Canada) and the Breath-A-Tech (Scott-Dibben, Australia). These assessments will be carried out to meet the standards of regulatory bodies worldwide (including the FDA). Secondly, we propose to perform extensive in vivo studie: filter studies to assess drug delivery to the patient; deposition studies to measure drug deposition in the lungs; and a pilot clinical trial to assess the efficacy of the device during medium to long-term use in children aged 2-8 years.Read moreRead less
A Randomized Controlled Trial Of Effects Of Early Life Exposure To General Anaesthesia On Neurobehavioural Outcomes In Children With Cystic Fibrosis (CF)
Funder
National Health and Medical Research Council
Funding Amount
$587,240.00
Summary
Anaesthesia permits surgeries and other interventional procedures that benefit the health of children to be performed painlessly and non-traumatically. This study will provide critical information about whether the drugs used commonly for general anaesthesia represents a risk to very young children in terms of their neurobehavioural development.
Limiting Tuberculosis Transmission And Improving The Care Of Affected Children
Funder
National Health and Medical Research Council
Funding Amount
$412,419.00
Summary
Tuberculosis (TB) is the biggest infectious disease killer on the planet. Drug-resistant TB poses a particular challenge in the Asia-Pacific region. My research will assist Australia to progress towards domestic TB elimination. It will improve the management of “difficult to treat” cases and help to safeguard the public against ongoing TB transmission. Work in neighbouring countries will help to contain the spread of drug-resistant TB and protect vulnerable young children.
Invasive Staphylococcus Aureus Disease In Children; Epidemiology, Treatment And Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
This project will involve a systematic review of randomised controlled trials (RCT) on the treatment Staphylococcus aureus bacteraemia (SAB) as well as a local WA retrospective review to quantify disease burden, trends and outcome. A prospective 2-year multicentre Australian review will then identify variables that can predict complicated and uncomplicated SAB. This information will then be used to design a RCT protocol on risk-stratified treatment approaches for SAB in paediatrics.
Bio-molecular Studies For Improved Diagnosis And Management Of Australian Children With Fish Allergy
Funder
National Health and Medical Research Council
Funding Amount
$496,602.00
Summary
Allergy to fish among children is often life-long and emerging as a significant healthcare issue worldwide, while management of fish allergy is challenging due to the lack of reliable diagnostic assays. This research grant will lead to the development of novel diagnostics for fish allergy in Australia, addressing aspects of the worldwide food allergy epidemic and forms the ideal platform for the study of fish specific allergens, generating novel knowledge for greatly improved patient management.
Understanding The Mechanisms Of Bleeding And Clotting Complications For Children On Extracorporeal Circuits.
Funder
National Health and Medical Research Council
Funding Amount
$1,113,385.00
Summary
Extracorporeal Membrane Oxygenation (ECMO) is advanced life support, which can save critically ill children. Significant bleeding occurs in 39%; clotting in 31% of children on ECMO; stroke in 12%. The biggest barrier to reducing these complications is the lack of understanding of how the bleeding/clotting system works in ECMO. This unique proposal uses the largest paediatric ECMO population in Australia and a multidisplinary expert team to develop a mechanistic understanding of these issues.