Exploring The Causal Pathways To Cutaneous Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$159,171.00
Summary
Melanomas are cancers arising from the pigment cells of the skin, and are among the most commonly occurring cancers in this country. Each year, more than 8000 Australians are diagnosed with invasive melanoma, resulting in some 900 deaths annually. Survival from melanoma is high if the disease is detected early (5 yr survival for thin melanomas-94%), however survival rates for thicker tumours are significantly worse, and for metastatic disease, very poor (<10%). Sunlight is the principal facto ....Melanomas are cancers arising from the pigment cells of the skin, and are among the most commonly occurring cancers in this country. Each year, more than 8000 Australians are diagnosed with invasive melanoma, resulting in some 900 deaths annually. Survival from melanoma is high if the disease is detected early (5 yr survival for thin melanomas-94%), however survival rates for thicker tumours are significantly worse, and for metastatic disease, very poor (<10%). Sunlight is the principal factor which causes this disease, although there is increasing evidence that the role of sunlight in causing melanoma is not the same for all people who develop this disease. A new hypothesis proposes that the malignant course of melanomas may reflect their causal origins, with melanomas induced by chronic sunlight exposure perhaps being more aggressive than other melanomas. We will undertake a large study of patients with melanoma to investigate both the causal pathways to melanoma and their influence on markers of tumour aggressiveness. We will capture detailed information about the microscopic appearance of the melanomas from pathologists at the time of diagnosis, and marry this to the information reported by the patients about their past history of sun exposure. When complete, this study will provide new information about the causes of melanoma. Such knowledge is crucial to controlling and preventing this cancer.Read moreRead less
Characterisation Of The Cellular Changes Induced By Ultraviolet A Radiation
Funder
National Health and Medical Research Council
Funding Amount
$448,500.00
Summary
Sunlight is an important environmental health hazard as it causes immunosuppression and cancer. It suppresses our ability to destroy developing cancers. Australia has the highest incidence of skin cancer in the world, 66% of Australians develop skin cancer during their lifetime. The relationship between UV dose, wavelength and cancer in humans is unknown. As this cannot be directly experimentally determined in humans, surrogate biological endpoints such as immunosuppression will help determine t ....Sunlight is an important environmental health hazard as it causes immunosuppression and cancer. It suppresses our ability to destroy developing cancers. Australia has the highest incidence of skin cancer in the world, 66% of Australians develop skin cancer during their lifetime. The relationship between UV dose, wavelength and cancer in humans is unknown. As this cannot be directly experimentally determined in humans, surrogate biological endpoints such as immunosuppression will help determine the damaging wavebands within sunlight. There has been little work on the effect of UVA on health or the mechanisms of action of UVA compared to UVB. A recent consensus UVA working group of 80 international participants convened by the American Academy of Dermatology out of concern about the lack of knowledge of UVA on human health concluded that the action spectrum for photocarcinogenesis and photoageing, particularly the efficacy of UVA in humans remains to be elucidated, and that more funding should be provided for radiation biology research to help elucidate UVA mechanisms of injury. Similarly a recent expert meeting (including Prof. Halliday) convened by the International Agency for Research on Cancer (WHO) on sunscreen protection from skin cancer recommended that studies should be conducted on the effects of exposure to UVA in causing both photoageing and skin cancer which followed from their major recommendation that it is important to understand the nature of the dose-response relationship on risk and the action spectrum for each effect . The studies described in this project will contribute to these recommendations.Read moreRead less
CDK4 Activity In S/G2 Phases Influences Mitotic Fidelity
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The ultraviolet radiation component of the sunlight is a major environmental factor in the development of skin cancers, including melanomas. Over the past 10 years a genetic factors have also been identified that predispose towards developing melanoma, although the connection between ultraviolet radiation and the genetic factors has remained elusive. In this study we will investigate a cellular mechanism that potentially explains the link between sunlight exposure and one of the genetic risk fac ....The ultraviolet radiation component of the sunlight is a major environmental factor in the development of skin cancers, including melanomas. Over the past 10 years a genetic factors have also been identified that predispose towards developing melanoma, although the connection between ultraviolet radiation and the genetic factors has remained elusive. In this study we will investigate a cellular mechanism that potentially explains the link between sunlight exposure and one of the genetic risk factors. We will also examine whether targeting the pathway this genetic factor normally operates in can deliver increased therapeutic benefit to an existing chemotherapeutic treatment.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 The Mast Cell Product Histamine In Ultraviolet Radiation Induced Systemic Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise ab ....The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise able to reject the great majority of UV-induced skin cancers. This effect of UV radiation on the immune system may be relevant to other diseases. It may alter the course of some infections, change the way the body responds to vaccination, and may also have a role in some immune-related diseases such as multiple sclerosis. How it is that these wavelengths just beyond visible light can affect the immune system is the subject of this project. We know that UV radiation can penetrate only a short way into the skin, yet can have widespread effects on the immune system. Our research to now has shown that a particular cell type sitting just below the surface of skin, the dermal mast cell, is essential. We've also demonstrated some of the complexity of the early response to UV exposure - both a chemical (cis-urocanic acid) in the very outermost layer of skin, and nerves in the skin, have roles. Importantly, anti-histamines can inhibit UV effects on immune responses. Additional lines of evidence also point to histamine, a product of mast cells, as playing a pivotal role in the immune alterations following UV exposure. Our research aims to characterise the effects of histamine on cells central to the development of immune responses, known as dendritic cells, and define the mechanisms of the effect in experimental models. In collaboration with researchers in the UK, we will further characterise the role of mast cells in UV alterations to immunity in humans.Read moreRead less
Sunscreen Immune Protection Factor Prediction Of Inhibition Of Anti-tumour Immunity And Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$186,372.00
Summary
Despite sunscreens having been used in Australia for more than 25 years the incidence of skin cancer continues to increase. This is partly due to the long lag time in developing a skin cancer, so that the current incidence reflects sun exposure patterns of many years ago. However this is also partly due to sunscreens not being as effective at preventing skin cancer as they are at preventing sunburn. The ultraviolet wavelengths found in sunlight are the prime cause of skin cancer. Australians are ....Despite sunscreens having been used in Australia for more than 25 years the incidence of skin cancer continues to increase. This is partly due to the long lag time in developing a skin cancer, so that the current incidence reflects sun exposure patterns of many years ago. However this is also partly due to sunscreens not being as effective at preventing skin cancer as they are at preventing sunburn. The ultraviolet wavelengths found in sunlight are the prime cause of skin cancer. Australians are exposed to high levels of sunlight, and consequently 66% of Australians develop skin cancer throughout their lifetime. For this reason, Australia has been dubbed the Skin Cancer Capital of the World. To reduce the incidence of skin cancer in Australia, it is recommended that individuals use sunscreens. The means of assessing the effectiveness of sunscreens is based on an SPF system, which measures the ability of sunscreens to prevent sunburn (erythema). However sunburn is induced by particular ultraviolet wavelengths, and may not be as important for skin cancer assessment as other damaging effects of sunlight, such as immunosuppression and genetic mutations. Sunscreens should be tested for protection from immunosuppression as well as sunburn, as this would aid the development of better sunscreens. We have developed the technology to measure protection of the immune system, and intend to investigate the usefulness of this new sunscreen test.Read moreRead less