Effect Of Ultraviolet Radiation On Development Of Effector And Memory T Cells To Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$498,328.00
Summary
Australia has the highest incidence of skin cancer in the world, due to our lifestyle that involves high levels of exposure to sunlight. Skin cancer, including melanoma can be destroyed by the immune system, but sunlight inhibits immunity, enabling skin tumours to grow. Our aim is to determine how sunlight affects the activation of effector anti-melanoma T cells, and their development into memory T cells, and the dose of sunlight required to have this effect. It is unknown whether ultraviolet ra ....Australia has the highest incidence of skin cancer in the world, due to our lifestyle that involves high levels of exposure to sunlight. Skin cancer, including melanoma can be destroyed by the immune system, but sunlight inhibits immunity, enabling skin tumours to grow. Our aim is to determine how sunlight affects the activation of effector anti-melanoma T cells, and their development into memory T cells, and the dose of sunlight required to have this effect. It is unknown whether ultraviolet radiation in sunlight suppresses the activation of effector cells that mediate rejection of skin tumours, or their development into memory cells, or migration of activated-memory lymphocytes into skin tumours. The number of antigen reactive T cells is a key issue for tumour immunity and the aim of many clinical immunotherapy trials is to boost these to levels that can effectively destroy the tumour. It is important to establish whether low doses of sunlight readily achievable during normal living, or only higher exposures received when sunbaking, inhibit the number of these effector T cells, and their migration into skin tumours. It is important to determine whether there is a relatively safe threshold level of sunlight exposure to be able to give better advice on sunlight doses that can be achieved without causing serious deleterious health effects. Also these levels of sunlight may interfere with immunotherapy trials and therefore need to be determined. An additional outcome will be to determine whether chemopreventative agents that enhance recovery from sunlight induced suppression of skin allergies are also protective for anti-tumour immunity. The establishment of procedures for prevention of suppression of anti-tumour immunity may enhance the number of T cells activated by natural immunity or during immunotherapy, thereby improving immune rejection of melanoma.Read moreRead less
Investigating The Utility Of Primary Care Skin Cancer Clinics In Queensland
Funder
National Health and Medical Research Council
Funding Amount
$187,000.00
Summary
Skin cancer is the most common cancer in Australia, with an estimated 375,000 people being treated for some skin cancer in Australia in 2002, and 1462 dying from the disease (mainly from melanoma) in 2001. Australia has the highest rate of skin cancer, both melanoma and non-melanoma is the world. However, if detected early, skin cancer is curable, and the focus of current treatment programs internationally is to detect the disease before it progresses to an advanced stage. A large proportion of ....Skin cancer is the most common cancer in Australia, with an estimated 375,000 people being treated for some skin cancer in Australia in 2002, and 1462 dying from the disease (mainly from melanoma) in 2001. Australia has the highest rate of skin cancer, both melanoma and non-melanoma is the world. However, if detected early, skin cancer is curable, and the focus of current treatment programs internationally is to detect the disease before it progresses to an advanced stage. A large proportion of skin cancers are first detected by the non-medical community. However, due to the two-tiered medical system in Australia, a person first seeks medical opinion from a general practitioner (GP), who acts as a gatekeeper for further treatment from a specialist. Therefore the ability of GPs to be able to discern which lesions require further treatment is crucial, both for the patient, and the financial burden on the health system. A recent development has been the establishment of dedicated primary skin care clinics, which offer open access consultations to the community for the diagnosis and treatment of skin cancers and pigmented lesions. The emergence of these clinics has created much debate in the medical media. Concern has been expressed about the skills of practitioners in these clinics, whilst others argue that sub-specialisation in primary care will lead to improvements in the management of patients. As there is currently no data on the volume, casemix and diagnostic accuracy of these clinics it is difficult to assess the diagnostic ability of skin cancer clinics. This will be the first project to quantify the role of skin clinics in the diagnosis of skin cancer in the community, and in particular their case volume, casemix and diagnostic accuracy, and assess these measures in relation to a comparable sample of general practitioners. Queensland is an ideal location for a study of this type due to its high incidence of both types of skin cancer.Read moreRead less
The Sentinel Lymph Node Territories Of The Whole Body And Their Clinical Implications: A Human Cadaver Study
Funder
National Health and Medical Research Council
Funding Amount
$602,984.00
Summary
Lymph gland screening with isotopes (Lymphoscintigraphy) has revealed unexpected pathways of cancer spread. This study, using an X-ray injection technique in human cadavers, is re-evaluating the outdated Melways Roadmap of lymph vessel pathways. The aims are to give accurate predictions of cancer spread, explain unusual clinical manifestations and to provide a new method of treating lymphoedema, the incapacitating swelling of limbs that may complicate lymph gland surgery or radiotherapy.
Pre-clinical Evaluation Of Nano-membrane Dressings To Promote Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$188,600.00
Summary
This project will investigate whether a novel type of wound dressing can promote faster wound healing and reduce scarring. Time taken to heal is one of the best predictors of whether a wound will heal with significant scarring. The faster wounds heal the better. We have identified a new dressing with specific nano-scale pores that may promote faster healing. This dressing will be tested in the best model of human wound healing with the potential to progress to clinical trials if successful.
This is a study of the senses which arise from our muscles and which tell us where our different body parts are, at any point in time. These senses, collectively called proprioception, are also involved in the automatic, unconscious control of our muscles. So, ultimately, they allow us to stand and to move freely with precision and confidence, even in the dark. One of these senses, the sense of effort or of heaviness, is believed to be generated within the brain. It intensifies when we become fa ....This is a study of the senses which arise from our muscles and which tell us where our different body parts are, at any point in time. These senses, collectively called proprioception, are also involved in the automatic, unconscious control of our muscles. So, ultimately, they allow us to stand and to move freely with precision and confidence, even in the dark. One of these senses, the sense of effort or of heaviness, is believed to be generated within the brain. It intensifies when we become fatigued. These experiments will be concerned with finding out more about how this works. We have a method that uses magnetic stimulation of the brain to change its control of our muscles. Using it we will learn how this sense is generated. When we close our eyes and move our limbs we realise that we know exactly where they are at any point in time. It remains uncertain exactly how this information is generated within the nervous system. One idea, arising from some recent experiments which we want to test, is that as we move the limb, the skin over the moving parts is stretched and stretch-sensitive nerve endings in the skin provide us with information about the movement. Alternatively, perhaps it is the effort we exert to maintain limb position against the force of gravity which tells us where the limb is. In another recent study we have found that when a muscle has become painful from excessive exercise or from some local strain injury, our ability to control the muscle and so move the limb is no longer as effective. We want to study the underlying nervous mechanisms responsible for the changes in movement control. Are they designed to spare the muscle while it recovers from injury? How are they brought about? All of this work is important for a better understanding of ourselves, for a better clinical diagnosis when something goes wrong and for improved treatment of diseased or injured muscles.Read moreRead less
Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blo ....Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blocked with the ultimate goal to cure the disease. Using an experimental model of pernicious anaemia in mice, where the basic pathology is immune-mediated gastritis, the disease will be treated by presenting the disease causing autoantigen via modified, or immature, antigen presenting cells to the immune system. In other experimental models which form the background to this project we have shown that this approach leads to down-regulation of the immune response by generating cells which specifically suppress the immune system. In our studies of autoimmune gastritis we will obtain modified antigen presenting cells from the skin, the blood, the spleen and thymus and use these cells to define optimal conditions for presenting the auto-antigen molecules to achieve the ultimate goal, which is antigen specific suppression of autoimmune gastritis. Our hypothesis is that immature antigen presenting cells are unable to present antigen to induce an effective immune response, but instead induce a response that results in antigen specific suppression. We intend to use this antigen specific suppression to prevent the establishment of autoimmune gastritis as well as treatment of established disease. This is a unique and potentially valuable strategy to treat autoimmune gastritis and offers the potential to apply this approach to other autoimmune conditionsRead moreRead less