The Ability Of Sunscreens To Protect Against The Induction Of Solar Irradiation-induced Melanocytic Naevi In Vivo.
Funder
National Health and Medical Research Council
Funding Amount
$106,854.00
Summary
Melanoma is an increasing problem in Australia. Strong evidence supports the finding that the number of moles on skin is a good indicator of future melanoma risk and a short term marker of adverse reactions to melanoma-inducing sun exposure in humans. While recommendations for sun protection have been proposed for many years, it is currently unknown what component of sunlight induces melanoma or whether sunscreens protect against the formation of melanoma. Using an animal model for human moles o ....Melanoma is an increasing problem in Australia. Strong evidence supports the finding that the number of moles on skin is a good indicator of future melanoma risk and a short term marker of adverse reactions to melanoma-inducing sun exposure in humans. While recommendations for sun protection have been proposed for many years, it is currently unknown what component of sunlight induces melanoma or whether sunscreens protect against the formation of melanoma. Using an animal model for human moles of the skin we aim in contributing to the answers of these two questions .Read moreRead less
The Role Of MIC-1 In The Promotion And Progression Of Skin Squamous Cell Carcinoma.
Funder
National Health and Medical Research Council
Funding Amount
$237,258.00
Summary
Skin cancers are the most common human tumours and the incidence is increasing. Ultra-violet (UV) light is the main factor in the formation of skin cancer. This project will find how a gene product (MIC-1) induced by solar UV affects the skin, and why we see it in skin cancers. This protein has other interesting properties that could bear directly on measuring sun exposure and understanding skin cancer. A processed form is released into the blood, where it could carry UV signals and be used in p ....Skin cancers are the most common human tumours and the incidence is increasing. Ultra-violet (UV) light is the main factor in the formation of skin cancer. This project will find how a gene product (MIC-1) induced by solar UV affects the skin, and why we see it in skin cancers. This protein has other interesting properties that could bear directly on measuring sun exposure and understanding skin cancer. A processed form is released into the blood, where it could carry UV signals and be used in population studies as a measure of sun exposure. It's also induced by certain cancer-promoting chemicals which resemble UV light in their immediate effects. A lot could therefore be learnt from this protein, and if we find that MIC-1 promotes the growth of normal and tumour cells in the skin after UV exposure, we can look for ways to stop this happening.Read moreRead less
Adult non-Hodgkin?s lymphoma (NHL) is one of the most rapidly increasing cancers of recent times. The rise has occurred worldwide in men and women of all ages. The reason for most of the rise is unknown. It has recently been proposed that part of the upsurge may be due to increases in sun exposure which have occurred during the same period. There is some indirect evidence to support this hypothesis. For example, the rate of occurrence of NHL is higher closer to the equator in Australia than it i ....Adult non-Hodgkin?s lymphoma (NHL) is one of the most rapidly increasing cancers of recent times. The rise has occurred worldwide in men and women of all ages. The reason for most of the rise is unknown. It has recently been proposed that part of the upsurge may be due to increases in sun exposure which have occurred during the same period. There is some indirect evidence to support this hypothesis. For example, the rate of occurrence of NHL is higher closer to the equator in Australia than it is in England and Wales, and NHL is diagnosed more frequently among British migrants to Victoria than it is in their homeland. The sunlight hypothesis will be tested by comparing the pattern of sun exposure in Tasmanians diagnosed with NHL during the years 1998-2001 and in a sample of Tasmanians without the disease. tasmania has been chosen because levels of ultraviolet (UV) radiation are low there in all but the summer months, when it approaches the levels of Brisbane, Sydney and Melbourne. There is therefore a greater difference in UV exposure between the most exposed and the least exposed in Tasmania, making it an ideal location to test the hypothesis. The link between NHL and a measure of melanin pigmentation in the skin will also be studied. The incidence of NHL is higher in lighter-skinned ethnic groups than it is in darker-skinned people living at the same latitude, but it is not known whether risk varies within Caucasian populations. A new measure of melanin in the skin, developed at the Menzies Centre for Population Health Research in Hobart, will better allow the effects of skin colour to be studied.Read moreRead less
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
Pterygia, one of the most common ocular complaints in Australia and worldwide, are thought to originate from overexposure to UV light. We propose that UV-irradiation stimulate certain cells in the eye to produce cytokines, growth factors and enzymes which degrade scaffold proteins such as collagens. These enzymes may play a key role in the progressive and invasive nature of pterygia. Dissecting the mechanism(s) by which UV light induces these proteins will lead to new and more reliable therapies ....Pterygia, one of the most common ocular complaints in Australia and worldwide, are thought to originate from overexposure to UV light. We propose that UV-irradiation stimulate certain cells in the eye to produce cytokines, growth factors and enzymes which degrade scaffold proteins such as collagens. These enzymes may play a key role in the progressive and invasive nature of pterygia. Dissecting the mechanism(s) by which UV light induces these proteins will lead to new and more reliable therapies for the treatment of pterygia.Read moreRead less
Susceptibility Of The Basal Layer Of Human Epidermis To UVA Oxidative Damage Due To Pheomelanin And Suboptimal DNA Repair
Funder
National Health and Medical Research Council
Funding Amount
$559,354.00
Summary
Australia has the highest incidence of skin cancer in the world. It is important to understand how sunlight causes skin cancer and the wavelengths involved in order to devise effective preventative and therapeutic strategies. Our proposal is that the cells in the skin that give rise to the most common forms of skin cancer, squamous cell carcinoma and basal cell carcinoma, are particularly vulnerable to UVA. We aim to study why this is the case and whether this vulnerability can be prevented.
Role Of Brm In Skin Tumour Progression From Benign To Malignant
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that ....Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that can spread to other tissues and are potentially fatal. Little is known about the biological mechanisms involved in solar keratosis development into squamous cell carcinomas. We have identified the gene brm as being involved in this process. It has not previously been recognised that this gene is important for skin cancer development and therefore our preliminary studies have identified a potential new target. We will study the role of this gene in ultraviolet radiation induced skin carcinogenesis, determine whether it is mutated by ultraviolet radiation in human skin cancer, and what role in plays in some key biological processes in skin cancer development. This study will expand our understanding of malignant conversion during human skin carcinogenesis, the most prevalent human cancer in Australia.Read moreRead less
DNA Damage Induced By UVA And UVB In Squamous Cell Carcinoma Progression
Funder
National Health and Medical Research Council
Funding Amount
$65,000.00
Summary
Australia has the highest incidence of skin cancer in the world. This results from immigration of individuals with fair skin to Australia. Skin cancer is three times as common as all other cancers combined. Overall, the incidence of skin cancer continues to rise in Australia and it will be several years before the true effectiveness of preventative programs are known. In the meantime, 1000 Australians die each year from skin cancer. Modern sunscreens, even those with high SPF and labelled as bro ....Australia has the highest incidence of skin cancer in the world. This results from immigration of individuals with fair skin to Australia. Skin cancer is three times as common as all other cancers combined. Overall, the incidence of skin cancer continues to rise in Australia and it will be several years before the true effectiveness of preventative programs are known. In the meantime, 1000 Australians die each year from skin cancer. Modern sunscreens, even those with high SPF and labelled as broad spectrum do not protect very well from UVA, though they are very effective UVB filters. Most sunscreens absorb or reflect only about 50% as much UVA as UVB. Thus sunscreen use alters the spectrum of UV received. This is an important issue, because if sunscreens are used to prolong sun exposure they will selectively increase the amount of UVA reaching the skin, and the sun contains a lot more UVA than UVB. There is only limited evidence to suggest they protect from skin cancer in humans whereas there is good evidence that they protect from precursor lesions. We have developed a new hypothesis, that UVB is primarily responsible for development of preneoplastic lesions (solar keratosis and dysplastic nevi) whereas UVA plays a relatively more important role in their progression to malignancy. This hypothesis would explain why sunscreens are more effective at preventing nevi and solar keratosis formation than they are at preventing melanoma and squamous cell carcinoma. Until the action spectrum defining the wavelengths responsible for skin cancer induction is known, the optimal methods for protection from skin cancer will be difficult if not impossible to design. That different wavelengths may be involved in different phases of skin cancer development in humans is a novel hypothesis: if it is correct it will have profound implications for both the design of sunscreens and our current public health programmes for skin cancer prevention.Read moreRead less