Prediction Of Clinical Radiosensitivity Caused By Ionising Radiation During Radiotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation bio ....Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation biology research is to develop efficient predictive measures that could identify radiosensitive individuals prior to treatment. This predictive ability would enable the individualisation of radiotherapy radiation doses, which should result in improvement of tumour control rates and a reduction in the incidence of side effects associated with radiotherapy. We aim to understand radiosensitivity at the molecular level using the powerful technology of microarrays. Using microarray technology, thousands of genes can be tested for expression activity simultaneously. We have a unique tissue bank established from many radiosensitive and non-sensitive control radiotherapy patients. The use of microarray technology on samples from this unique tissue bank may enable the gene expression pattern of individuals that display radiosensitivity to be distinguished from the rest of the population. In conjunction, two additional tests will be used to determine who is susceptible to radiosensitive reactions which include assessment of a DNA repair pathway and assessment of the length of the telomeres (Caps on the ends of the chromosomes), both of which have been shown to be involved with radiosensitivy. This experimentation will hopefully lead to the development of a predictive assay for use in the clinic for cancer patients prior to receiving radiotherapy.Read moreRead less
Radiotherapy (RT) is a curative anti-cancer treatment employed in around half of all cancer sufferers. Very occasionally, a cancer patient will manifest an unexpected adverse reaction to RT and there is strong evidence for a genetic basis to such RT sensitivity. Despite two decades of research, such reactions cannot currently be predicted prior to treatment and their occurrence limits the intensity, and hence cure rates, of RT for the majority of patients. This project will employ cutting edge t ....Radiotherapy (RT) is a curative anti-cancer treatment employed in around half of all cancer sufferers. Very occasionally, a cancer patient will manifest an unexpected adverse reaction to RT and there is strong evidence for a genetic basis to such RT sensitivity. Despite two decades of research, such reactions cannot currently be predicted prior to treatment and their occurrence limits the intensity, and hence cure rates, of RT for the majority of patients. This project will employ cutting edge technology (DNA Chips, or microarrays) to attempt to understand why some patients suffer significant RT side-effects, while the vast majority do not. We have developed a tissue bank of samples from cancer patients who have had adverse RT reactions, and these samples (and samples from unaffected cancer patients) will be examined by microarrays: the activity of thousands of genes will be evaluated in each experiment, and we shall search for patterns of gene activity which track with RT sensitivity. Should we determine a pattern, this pattern will be checked against a larger number of cases and if it accurately predicts RT sensitivity, could lead to the routine testing of cancer patients prior to RT and the individualisation of cancer therapy. In parallel, we will evaluate the tissues of sensitive patients with assays capable of detecting abnormalities in the response to radiation, which may give clues as to an underlying gene fault(s) which might predispose to radiosensitivity in that individual.Read moreRead less
Molecular Profiling Of Sarcomas To Enable Clinical Prediction And Elucidate Molecular Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
Sarcomas are uncommon cancers which affect the young, with a 50% mortality. Treatment involves an expert multidisciplinary approach, and even when effective often entails long-term loss of quality of life. Most sarcomas are treated with a combination of radiotherapy and surgery, which improves survival significantly compared to surgery alone. Radiotherapy does not help all patients, has side-effects and is expensive and time consuming. It would be useful to be able to identify patients who will ....Sarcomas are uncommon cancers which affect the young, with a 50% mortality. Treatment involves an expert multidisciplinary approach, and even when effective often entails long-term loss of quality of life. Most sarcomas are treated with a combination of radiotherapy and surgery, which improves survival significantly compared to surgery alone. Radiotherapy does not help all patients, has side-effects and is expensive and time consuming. It would be useful to be able to identify patients who will not benefit from radiotherapy, to minimise unnecessary harm from treatment and offer alternate more effective therapies. Unfortunately, we cannot yet distinguish which tumours will respond and which will not. Moreover, the uderlying causes of sarcoma are poorly understood. This project has two aims: first to make our current therapies more effective by targeting those who will not benefit from standard treatment; and second to better understand the causes of sarcoma, in order to develop better treatment. Microarrays enable the simultaneous study of thousands of genes, which when combined form a unique portrait of each tumour. Our unit, one of the largest sarcoma sevices in Australia, has access to large numbers of tumour samples, with excellent basic science support. It is now possible to ask what the molecular 'portrait' is of sarcomas which are responsive to radiotherapy, using tiny amounts of tumour material which can be obtained before treatment starts. We also hope to identify the molecular basis of sarcomas by finding the key genes whose inactivation is central to the development of this form of cancer. Such genes can then form the basis of targeted therapy. This approach will lay a solid foundation for future research into sarcomas, and has the potential to reduce unnecessary cost and suffering patients experience from treatments which are unlikely to be effective.Read moreRead less
The Role Of Interleukin-21 In The Pathogenesis Of Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$489,060.00
Summary
Interleukin-21 (IL-21) is a soluble protein that is produced by cells enabling them to communicate with other cells. IL-21 helps cells to clear viruses and bacteria from the body. However, our studies show that IL-21 also generates T cells that destroy beta cells and cause diabetes. IL-21 is produced at abnormally high levels in an important murine model of spontaneous type-1 diabetes (T1D) and if we block IL-21 we prevent diabetes. This projects' aims assess IL-21 as therapeutic target for T1D.
Inter-rater Reliability And Predictive Validity Of A New Functional Capacity Evaluation For Chronic Back Pain
Funder
National Health and Medical Research Council
Funding Amount
$105,794.00
Summary
Back pain costs the Australian community tens of billions of dollars. Back pain is one of the main causes of work injury and lost time from work. The longer a person is off work, the harder it is to get them back to work. Workers' compensation systems around Australia aim at getting the injured worker with back pain back to work as soon as possible. One of the difficulties in this process is determining what the person with back pain can physically do in the workplace. An evaluation technique, c ....Back pain costs the Australian community tens of billions of dollars. Back pain is one of the main causes of work injury and lost time from work. The longer a person is off work, the harder it is to get them back to work. Workers' compensation systems around Australia aim at getting the injured worker with back pain back to work as soon as possible. One of the difficulties in this process is determining what the person with back pain can physically do in the workplace. An evaluation technique, called functional capacity evaluation (known as FCE), is one method used to find out what the person with back pain physically can and cannot do. In a FCE, a trained health professional such as an occupational therapist, observes the person performing a range of physical activities like the ones he or she may have to perform in a job. The therapist closely observes the person performing activities such as lifting, carrying, kneeling, crouching, balancing, and walking and notes any limitations in the person's ability to complete the activities. The therapist makes comments about what difficulties the person may have on the job and recommendations about how these could be reduced or eliminated. The information gained from these evaluations can be valuable for the treating doctor in deciding whether the person is ready to go back to work and what duties the person can and cannot do on the job. Because of such value they provide, FCE is commonly used in rehabilitation programs endorsed by workers' compensation systems around Australia. This widespread use and endorsement of FCE occurs despite limited research on the soundness of the ratings made from these evaluations. There is a need to see whether recommendations made from FCEs are consistent between therapists (i.e. reliable) and to see if the FCE accurately predicts the person's physical capacity for work. This research will examine these issues with injured workers with back pain.Read moreRead less
From Maps To Efficient Multi-parasite Control In The Philippines
Funder
National Health and Medical Research Council
Funding Amount
$358,121.00
Summary
Schistosomiasis and soil-transmitted helminths are major parasitic infections in Asia, causing anaemia, poor growth and poor school performance and death in some chronic schistosomiasis cases. We will use maps to demonstrate the geographic distribution of these parasites in the Philippines. We will estimate the impact and costs and benefits of parasite control programmes. This research will help plan more efficient parasite control and reduce the impact of these infections in the Philippines.