Sun Exposure, Vitamin D And The Outcome Of Prostate Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$494,698.00
Summary
We will find out whether hours of sun exposure, reported in a standard interview by men with prostate cancer, reduces prostate cancer recurrence and progression. For any effect of sun exposure ithat we observe, we will find out whether it works through vitamin D, which is produced by sunshine on the skin, or is affected by changes in the vitamin D receptor gene, which produces the protein the binds with vitamin D on cells and makes it work. Prostate cancer is the most common cancer in men in Aus ....We will find out whether hours of sun exposure, reported in a standard interview by men with prostate cancer, reduces prostate cancer recurrence and progression. For any effect of sun exposure ithat we observe, we will find out whether it works through vitamin D, which is produced by sunshine on the skin, or is affected by changes in the vitamin D receptor gene, which produces the protein the binds with vitamin D on cells and makes it work. Prostate cancer is the most common cancer in men in Australia, and this study, using two of the largest collections of clinical outcomes data for this disease, will inform researchers, clinicians and consumers about the possible benefits of sun exposure and Vitamin D in the prevention of recurrence or progression of prostate cancer. On present evidence, these effects are very plausible possibilities. It may also identify sub-groups of men in whom sun exposure or vitamin D might be particularly beneficial in improving outcome of prostate cancer.Read moreRead less
Mast Cells Determine Susceptibility To Induction Of Systemic Immunomodulation By UVB Radiation
Funder
National Health and Medical Research Council
Funding Amount
$194,993.00
Summary
The ultraviolet B component of sunlight causes an immunosuppression in humans such that UV-induced tumours develop. In a murine model, we have shown that dermal mast cells at the irradiated site are crucially important in the mechanisms by which UVB stimulates this immunosuppression. In this project we wish to study in more depth the mechanisms by which sunlight stimulates mast cells to produce molecules which in turn signal immunosuppressive events. We hypothesise that there is an intermediary ....The ultraviolet B component of sunlight causes an immunosuppression in humans such that UV-induced tumours develop. In a murine model, we have shown that dermal mast cells at the irradiated site are crucially important in the mechanisms by which UVB stimulates this immunosuppression. In this project we wish to study in more depth the mechanisms by which sunlight stimulates mast cells to produce molecules which in turn signal immunosuppressive events. We hypothesise that there is an intermediary by which sunlight stimulates mast cell activity; we hypothesise that cis-urocanic acid may be involved directly or indirectly in this process. There is considerable evidence that histamine may be the major product of mast cells involved in this process; however it is unknown whether its primary action is on keratinocytes (stimulating prostanoid production), antigen presenting cells or lymph node cells. This project will also investigate the relationship of studies with mice to UVB-induced systemic immunosuppression in humans. Non-sun-exposed skin from controls and patients with non-melanoma skin cancers will be examined and dermal mast cell prevalence evaluated; we hypothesise that people with high dermal mast cell numbers are more prone to immunosuppression and thus, the outgrowth of UV-induced non-melanoma skin cancers. We hypothesise that there may also be qualitative differences in the mast cells of UV-sensitive and UV-resistant individuals; variations may occur in the granule contents of neutral proteinases or cytokines. It is necessary that we better understand the basis of immune system modulation by UVB that allows non-melanoma skin cancer development as these patients have a 20-30% higher risk of death from other cancers.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
The Centre for Research Excellence in Sun and Health (CRESH) aims to build an evidence base that will lead to the development of regionally appropriate public health guidelines that will balance the adverse and beneficial effects of sun exposure to optimise the health of the Australian community.
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
Epidemiology Of Human Papillomavirus (Hpv), Ultraviolet (UV) Radiation In Relation To Non-Melanoma Skin Cancer
Funder
National Health and Medical Research Council
Funding Amount
$300,000.00
Summary
Queensland epidemiologist, Professor Adele Green is the winner of an Australian-European Union medical research grant that she will use to investigate prevention of skin cancer. The prestigious NHMRC grant is intended to support Australian researchers involved in European collaboration, which will benefit the Australian community. Professor Green and her research group will use the grant to participate in a large consortium led by Dr Jan Nico Bouwes Bavinck from Leiden in the Netherlands, with t ....Queensland epidemiologist, Professor Adele Green is the winner of an Australian-European Union medical research grant that she will use to investigate prevention of skin cancer. The prestigious NHMRC grant is intended to support Australian researchers involved in European collaboration, which will benefit the Australian community. Professor Green and her research group will use the grant to participate in a large consortium led by Dr Jan Nico Bouwes Bavinck from Leiden in the Netherlands, with teams of researchers based in Germany, England, Italy and France. The work of the consortium will focus on finding out whether Human Papilloma Virus plays a role in causing skin cancer. Professor Green and her team are working to discover the relationship between Human Papilloma Virus, which is a common virus of the skin and the commonest types of skin cancer. If the papilloma virus is found to cause skin cancer, this will open up new avenues for prevention. Although Australia is a world hot-spot for skin cancer, the disease is of concern to Europeans because it is the most common form of cancer in white-skinned people.Read moreRead less
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