DNA methylation is a mechanism used by many organisms, including humans, to keep certain regions of DNA inactive, i.e. in a state where they will not be read. Errors in this process may result in inappropriate inactivation of a gene, termed epimutation; this may occur even when no DNA sequence changes (i.e. mutations) are present. Some individuals are born with high levels of an epimutation that predisposes them to developing multiple cancers. Little is known about whether low levels of epimutat ....DNA methylation is a mechanism used by many organisms, including humans, to keep certain regions of DNA inactive, i.e. in a state where they will not be read. Errors in this process may result in inappropriate inactivation of a gene, termed epimutation; this may occur even when no DNA sequence changes (i.e. mutations) are present. Some individuals are born with high levels of an epimutation that predisposes them to developing multiple cancers. Little is known about whether low levels of epimutations (only a portion of the body's cells affected) are important in development of sporadic (common) cancer. The aim of this project is to determine the levels of epimutations in the normal tissues of healthy individuals, and compare these with the levels in normal tissues of people who have had certain types of cancers. In doing this we hope to find out if low level epimutations contribute to the risk of developing sporadic cancer.Read moreRead less
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
Evidence For Psychological And-or Educational Interventions For Cancer-related Fatigue: A Systematic Review
Funder
National Health and Medical Research Council
Funding Amount
$28,283.00
Summary
Potential benefits to the community: Fatigue is one of the most common and distressing symptoms experienced by people with cancer and can exacerbate the experience of other symptoms, negatively affect mood, and impact on function and quality of life. Understanding which interventions are effective in helping people cope with cancer-related fatigue is important to inform decision-making by consumers, clinicians working in palliative care and policy makers. Objectives: This study aims to systemati ....Potential benefits to the community: Fatigue is one of the most common and distressing symptoms experienced by people with cancer and can exacerbate the experience of other symptoms, negatively affect mood, and impact on function and quality of life. Understanding which interventions are effective in helping people cope with cancer-related fatigue is important to inform decision-making by consumers, clinicians working in palliative care and policy makers. Objectives: This study aims to systematically review the evidence for psychological and-or educational interventions for managing cancer-related fatigue. Methods: This study will use the Cochrane Collaboration’s methodology to search, critically appraise, and analyse randomised controlled trials of psychological and-or educational interventions. This will involve collaboration with consumers and with the Cochrane Pain, Palliative Care, and Supportive Care Collaborative Review Group. This review will inform decision-making at all levels, assist in research translation and identify further gaps in the research regarding this distressing symptom.Read moreRead less
Increasing Appropriate Screening For Colorectal Cancer Patients And First Degree Relatives. A RCT.
Funder
National Health and Medical Research Council
Funding Amount
$1,372,866.00
Summary
Adoption of guideline recommendations is difficult to achieve. This research aims to improve adherence to guideline recommendations for surveillance for people with colorectal cancer and screening in their first degree relatives using an educational intervention. People with colorectal cancer and their first degree relatives will be randomly assigned to an educational intervention or to usual care, and adherence to guideline recommendations will be compared between groups.
Randomised Trials Of Adjuvant Cytotoxic & Endocrine Therapy For Early N+ And N- Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$510,509.00
Summary
This application covers 4 adjuvant early breast cancer trials currently part of the Australian New Zealand Breast Cancer Trials Group's national research programme. These trials are international collaborations involving the International Breast Cancer Study Group (IBCSG). Two of the studies concern pre, peri and post-menopausal women with early breast cancer and no involved lymph glands (IBCSG 8 and 9), and two concern pre, peri and post-menopausal women with early breast cancer and involved ly ....This application covers 4 adjuvant early breast cancer trials currently part of the Australian New Zealand Breast Cancer Trials Group's national research programme. These trials are international collaborations involving the International Breast Cancer Study Group (IBCSG). Two of the studies concern pre, peri and post-menopausal women with early breast cancer and no involved lymph glands (IBCSG 8 and 9), and two concern pre, peri and post-menopausal women with early breast cancer and involved lymph glands (IBCSG 13 and 14). In the absence of a definitive cure, the largest gains will come from optimal use of current therapies and new therapies to improve survival, and where possible, to reduce morbidity without the loss of efficacy. These four trials can realistically expect to produce important gains with potential benefit to the many women who are diagnosed with early breast cancer each year. The active accrual period for these studies is complete but all patients are currently on life long follow-up. Patients accrued to trial 8 have a clinical assessment 3 monthly to 2 years, 6 monthly to 5 years, and then annually. For trials 9, 13 and 14 women have a clinical assessment 3 monthly during year 1, 6 monthly for year 2 and then annually.Read moreRead less
Preparing Cancer Patients For Clinical Decision Making: A Randomised Trial Of Preconsultation Preparation Packages.
Funder
National Health and Medical Research Council
Funding Amount
$228,427.00
Summary
Most cancer patients in Australia now expect and are told their cancer diagnosis. There is considerable variation in the extent to which patients are informed about treatment options and are involved in treatment decisions. It can be argued that a treatment decision should be based on the oncologist's knowledge and the patient's preference. Two possible models can achieve this optimal outcome: the oncologist decides treatment on the basis of information passed on to him-her from the patient (the ....Most cancer patients in Australia now expect and are told their cancer diagnosis. There is considerable variation in the extent to which patients are informed about treatment options and are involved in treatment decisions. It can be argued that a treatment decision should be based on the oncologist's knowledge and the patient's preference. Two possible models can achieve this optimal outcome: the oncologist decides treatment on the basis of information passed on to him-her from the patient (the enabled doctor), and the patient chooses treatment based on informaton provided by the doctor (the empowered patient). We have developed a booklet on 'how treatment decisions are made'. In a randomised trial, patients seeing an oncologist for the first time are given the booklet and shown a video of ' their' oncologist interviewing an actor patient. The subsequent consultation is audiotaped to study the effect of these interventions on patient and doctor behaviour. The results of this trial will inform the development of our new patient educational materials. We now plan to develop consultation preparation packages. Patients will be sent information at least 48 hours before their first appointment with an oncologist with the goal of helping patients to achieve their preferred involvement in the consultation. The complete package will contain four components : a booklet on how treatment decisions are made including an outline of the two treatment decision models, a question prompt sheet and recommendation to prepare a list of questions, a booklet on Patient Rights, and an introduction to the Cancer Centre. The effects of the total package, and of just the Cancer Centre component on patient preferences for information and involvement in medical decisions, their consultation behaviour, and patient and doctor satisfaction with decision making will be studied in a randomised trial with control patients receiving no preparatory materials.Read moreRead less