A Randomised Phase III Study Of Radiation Doses And Fractionation Schedules In Non-low Risk DCIS Of The Breast
Funder
National Health and Medical Research Council
Funding Amount
$1,751,209.00
Summary
Treatment of ductal carcinoma in-situ (DCIS), a preinvasive form of breast cancer, is aimed at preventing invasive cancer recurrence. Women with higher-risk DCIS have an increased risk of recurrence. This study aims to individualise treatment for women with DCIS to achieve long-term tumour control with minimal treatment toxicity. After local excision of DCIS, radiotherapy (RT) to the whole breast reduces the recurrence rate. However, it is unclear if escalating radiation dose to the tumour bed i ....Treatment of ductal carcinoma in-situ (DCIS), a preinvasive form of breast cancer, is aimed at preventing invasive cancer recurrence. Women with higher-risk DCIS have an increased risk of recurrence. This study aims to individualise treatment for women with DCIS to achieve long-term tumour control with minimal treatment toxicity. After local excision of DCIS, radiotherapy (RT) to the whole breast reduces the recurrence rate. However, it is unclear if escalating radiation dose to the tumour bed in higher-risk women increases tumour control. It is also uncertain if giving fewer but larger radiation doses over 3-4 weeks would achieve the same tumour control as the standard 5-7 week course of RT to improve patient convenience and access to RT. Thus, this multicentre study of 610 women with higher-risk DCIS will investigate if adding a tumour bed radiation boost after whole breast RT improves tumour control, and the shorter RT course achieves the same tumour control as the standard longer course. Currently, the ability to predict the malignant potential of DCIS and RT toxicity is limited. This study will investigate if there are biological and genetic markers predictive of invasive recurrence and normal tissue toxicity in women with DCIS using state of the art technology. Women need to weigh up the likelihood of cancer control against adverse treatment effects to make an informed treatment decision. However, very little is known about the quality of life (QoL) consequences of the diagnosis and treatment of DCIS. In this study, the QoL, psychological distress, perceived risk of invasive cancer recurrence and perceived cosmetic outcomes of women with DCIS, will be assessed using a questionnaire of validated measures. This study will refine treatment for women with DCIS according to their risks of recurrence. It will significantly advance the understanding of the biology of DCIS and its psychological and QoL outcomes after treatment.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Epimutations As Germ-line Defects In Hereditary Cancer Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$385,925.00
Summary
Traditionally familial cancers were thought to be caused and inherited by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that a 'chemical coat' around the MLH1 gene, causing it to be switched off, can also be inherited in some cases of bowel cancer, without any mistakes within the gene's code. We will determine if this 'coat' causes other types of cancer and if this runs in families. We also hope to find out how the coat is formed and may be reversed.
MICROFABRICATED DEVICES: A SIGNIFICANT ADVANCE FOR THE DETECTION AND MOLECULAR ANALYSES OF CIRCULATING CANCER CELLS?
Funder
National Health and Medical Research Council
Funding Amount
$422,107.00
Summary
Using advanced microfabrication concepts, this project aims to develop a platform technology able to capture tumour cells circulating in the blood of cancer patients. Although present only in extremely small numbers, these cells provide invaluable insights into the pathophysiology of the disease and consequently provide vital diagnostic and prognostic information. Molecular analyses of these cancer cells could ultimately enable the design of improved and personalized cancer treatment.
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
Why Does Early Life Stress Aggravate Limbic Epileptogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$540,116.00
Summary
High rates of anxiety and depression occur in individuals with temporal lobe epilepsy (TLE), the most common form of focal epilepsy in adults. Rats that have experienced early life stress show increased anxiety, decreased seizure thresholds and accelerated epilepsy as adults. We have important leads to mechanisms. The proposed study will better understand the mechanisms connecting early life stress and psychiatric disease to adult TLE, and to test interventions that may counteract these effects.
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
Does Caffeine Affect The Development Of The Very Immature Brain: Dose Response Relationship?
Funder
National Health and Medical Research Council
Funding Amount
$668,386.00
Summary
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity (AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses of caffeine on the developing brain in a long-gestation species.
Evaluation Of The Effectiveness Of Mobile Preschool For Child Health And Development In Remote Aboriginal Communities
Funder
National Health and Medical Research Council
Funding Amount
$456,369.00
Summary
This project is a retrospective study of the effectiveness of the NT Mobile Preschool Program using assessment data for children's emergent literacy, social and emotional competencies and health status. Effectiveness will be established by comparison with achievement and health status data for children not attending preschool and those in communities with no preschool service. The study will identify and describe the key factors influencing the health and learning outcomes of the three groups.
Glycine Transporters regulate the concentration of glycine in the spinal cord and brain. It has been suggested that elevating glycine levels in these regions may be useful in treating pain and schizophrenia. This project will provide the basis for the development of new glycine transport inhibitors that may be used to treat these conditions.