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