Interaction Of Mc1r With The PRb And P53 Pathways In UVR-induced Melanoma Development
Funder
National Health and Medical Research Council
Funding Amount
$553,479.00
Summary
This project will shed light onto fundamental processes causing UV-induced melanoma (MM). Innate differences between individuals, independent of pigmentation, influence MM development. We will study the mechanisms of UVR-induced MM development in mice carrying gene mutations (Cdk4, Arf, Mc1r) that underpin human MM susceptibility. Knowledge of the sensitivity of an one's MCs to UV could be critical for targeting susceptible groups for health education campaigns and more intense screening.
Molecular Genetic Analysis Of BRCT Domain Function And RhoGEF Signalling In DNA-damage Response And Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
Cancers arise as a consequence of a series of genetic changes, usually by mutation of DNA. DNA is consistently exposed to an array of damaging agents, but the majority of mutations are corrected by cellular repair mechanisms. We now know that if these mechanisms work normally, too few mutations persist for cancer to result. However if these DNA damage repair mechanisms are themselves faulty, a high mutation rate occurs and a high risk of cancer results. DNA damage has another outcome. If the dam ....Cancers arise as a consequence of a series of genetic changes, usually by mutation of DNA. DNA is consistently exposed to an array of damaging agents, but the majority of mutations are corrected by cellular repair mechanisms. We now know that if these mechanisms work normally, too few mutations persist for cancer to result. However if these DNA damage repair mechanisms are themselves faulty, a high mutation rate occurs and a high risk of cancer results. DNA damage has another outcome. If the damage is too extensive, the cell commits suicide, not because it cannot function, but because it senses the DNA damage and chooses to die. One poorly understood aspect of the response to DNA damage is how the cell senses the damage and activates the suicide process. We have discovered a novel gene that appears to play a role in this sensing and suicide signalling process. The mouse version of this gene can itself act as a cancer-causing gene. We propose, however, to study the equivalent gene in Drosophila melanogaster, a more powerful experimental system, to characterise in detail its role in these processes. In this way we hope to generate a much more detailed understanding of the way that cells deal with DNA damage and choose suicide when the damage is too severe.Read moreRead less
First Ever System To Continuously And Directly Measure The Internal Anatomy To Guide Breast Cancer Radiation Treatment Under Deep Inspiration Breath Hold
Funder
National Health and Medical Research Council
Funding Amount
$409,766.00
Summary
We propose a first ever system to continuously and directly measure the internal anatomy of the patient during radiotherapy of left sided breast cancer to ensure correct position of patient and radiation beam. The proposed method involves no additional radiation dose to the patient. It relies on existing components of modern radiation treatment machines, requiring no additional equipment, which will make it easy to implement widely.
Improving Radiation Therapy Of Static And Moving Targets Using High Spatial Resolution Real-time Dosimeters
Funder
National Health and Medical Research Council
Funding Amount
$544,425.00
Summary
Radiation therapy is a major oncology modality for cancer treatment and more than 50% of cancer patients can benefit from radiotherapy at some stage of management. This project will develop two real-time, high spatial resolution dosimetry systems for quality assurance of contemporary radiation treatments of static and movable targets. It will be possible to minimize human and robotic system error so as to guarantee accurate cancer treatment delivery and improve the clinical outcomes of radiother ....Radiation therapy is a major oncology modality for cancer treatment and more than 50% of cancer patients can benefit from radiotherapy at some stage of management. This project will develop two real-time, high spatial resolution dosimetry systems for quality assurance of contemporary radiation treatments of static and movable targets. It will be possible to minimize human and robotic system error so as to guarantee accurate cancer treatment delivery and improve the clinical outcomes of radiotherapy.Read moreRead less
Translating Synchrotron Microbeam Radiation Therapy Into A Clinical Reality For Cancer Patients
Funder
National Health and Medical Research Council
Funding Amount
$337,896.00
Summary
The aim of this project is to translate an experimental radiotherapy technique, known as microbeam radiotherapy, into a clinical reality for the benefit of cancer patients world-wide. I propose to achieve this aim by working at the European Synchrotron Radiation Facility (ESRF) in France. The ESRF is Europe’s most powerful synchrotron light source, where a multi-disciplinary team of scientists and physicians are collaborating to treat the first human cancer patients with synchrotron radiation.
The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very si ....The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very simple. A drug which makes cells less sensitive to X-rays (these drugs are called radioprotectors) is simply applied topically to the normal tissues at risk. For this purpose, we have developed a new radioprotecting drug called methylproamine which is 100-fold more potent than previously-developed radioprotectors. Unfortunately, methylproamine is not suitable for our purpose because at higher concentrations it is toxic to some cells. This hurdle must be overcome in order to make the project attractive to potential commercial sponsors. Our aim is to modify methylproamine by removing the molecular features that cause the cytotoxicity. We have established that this is feasible, by synthesising and evaluating a small family of methylproamine analogues. Some less toxic family members have already been identified. With this knowledge, we now propose to use special computer programmes to design a much larger family of methylproamine analogues, and to synthesise and test each one in order to identify the most promising candidate for our purpose. Once the efficacy window hurdle is passed, the subsequent milestones to commercialisation and clinical implementation can be addressed, with appropriate sponsorship. An Australian company has already expressed strong interest and is evaluating the opportunity.Read moreRead less
X-RATE: A Novel Radiation Detector Platform To Realize New Opportunities In Radiotherapy At The Australian Synchrotron
Funder
National Health and Medical Research Council
Funding Amount
$347,541.00
Summary
Microbeam Radiation Therapy (MRT) is an emerging X-ray radiosurgery modality that offers new hope for the treatment of brain cancer and other human brain diseases. A tissue equivalent radiation dosimetry system is essential for upcoming MRT human trials to precisely verify treatment plans. We are recognized world leaders in real-time silicon detector instrumentation for radiation dosimetry. We plan to develop and demonstrate X-RATE, the X-ray Real-time Active Tissue Equivalent dosimeter.
REVEALING MOLECULAR MECHANISMS OF THE SYNCHROTRON RADIATION-INDUCED BYSTANDER EFFECT
Funder
National Health and Medical Research Council
Funding Amount
$429,294.00
Summary
Radiotherapy, a major treatment for more than half of cancer patients, is based on the dogma that radiation kills targeted cells. The radiation-induced bystander effect, by which the neighbours of irradiated cells can also damaged, is a new paradigm. What is the "danger signal" which induces DNA damage in un-irradiated normal tissues, and what minimal volume of tissue needs to be irradiated to induce bystander damage? The answers could have a major impact on optimising radiotherapy treatment.
Is Insulin Sensitivity In Children And Their Mothers Programmed By Maternal Blood Glucose?
Funder
National Health and Medical Research Council
Funding Amount
$169,630.00
Summary
Glucose intolerance in pregnancy is associated with the birth of large-for-dates and macrosomic (>4000g) babies. The risk of type 2 diabetes is greater in babies who are small or large at birth compared to those with normal birth weight. This study will determine if treatment of mothers with glucose intolerance in pregnancy (which is intermediate between normal glucose tolerance and diabetes) alters the regulation of glucose tolerance in their children. The mothers were randomised to receive ....Glucose intolerance in pregnancy is associated with the birth of large-for-dates and macrosomic (>4000g) babies. The risk of type 2 diabetes is greater in babies who are small or large at birth compared to those with normal birth weight. This study will determine if treatment of mothers with glucose intolerance in pregnancy (which is intermediate between normal glucose tolerance and diabetes) alters the regulation of glucose tolerance in their children. The mothers were randomised to receive normal antenatal care or to have their blood sugar measured and controlled by diet and insulin as for diabetics. We will measure the insulin sensitivity of the children to a glucose load. We will also measure blood pressure and lipids in these children. Treatment of the mother during pregnancy may alter the deposition of fat in the fetus the effect of which will continue into childhood. Thus the offspring of treated mothers may remain thinner throughout childhood. Each pregnancy increases a woman's chance of developing type 2 diabetes in later life. This risk is further increased by abnormal glucose tolerance during pregnancy. This study will test the long-term benefits of treatment during pregnancy of women with impaired glucose tolerance on the subsequent regulation of glucose tolerance. We shall invite women who took part in the Australian Carbohydrate Study in Pregnancy (ACHOIS) to return and have an intravenous glucose tolerance test. Insulin sensitivity and glucose tolerance will be determined and related to treatment of the impaired glucose tolerance in pregnancy. This study will be the first follow-up of a large randomised trial of treatments of impaired glucose tolerance in pregnancy. The potential long-term benefits are strategies to reduce the future chance of developing risk factors for type 2 diabetes, obesity and abnormal blood lipids in childhood and adult life. The study will establish the benefits or otherwise of tight control of blood glucose in pregnancy.Read moreRead less