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Skin cancer affects 60% of Australians. Nicotinamide (vitamin B3) prevents many of sunlight’s damaging effects and reduces premalignant keratoses by 35% compared to placebo in sun-damaged individuals. We now need to test whether nicotinamide can prevent skin cancer. Skin cancer patients will receive nicotinamide or placebo for 12 months and new cancers will be counted in each group. Nicotinamide is safe, widely available and an exciting opportunity for cost-effective skin cancer prevention.
Cancers of the skin are the most common tumours in humans, and their diagnosis and treatment impose the largest costs on Australia’s cancer budget. While much has been learned about the roles of sunlight and skin type as risk factors for skin cancer, relatively little is known about the genes conferring risk. This study will compare the genetic profiles of over 6000 patients with skin cancer to 3000 people without skin cancer to pinpoint the genes responsible for skin cancer.
Fighting Epidermal Skin Cancers By Targeting Epidermal Clones That Accumulate Mutations
Funder
National Health and Medical Research Council
Funding Amount
$1,149,373.00
Summary
Common skin cancers such as basal and squamous cell carcinomas (BCC and SCC) are by far the most frequent cancer worldwide and require over a million interventions per year in Australia. This project will identify the skin cells that are most susceptible to give rise to cancer if excessively exposed to the sun and explores ways to prevent cancer formation. This will inform on new strategies to prevent new skin cancer development.
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
Clinical Trial Of DZ13 DNAzyme Targeting C-Jun In Subjects With Basal Cell Carcinoma - DISCovery (Oligonucleotide Inhibition Of Skin Cancer) Study
Funder
National Health and Medical Research Council
Funding Amount
$74,365.00
Summary
Basal cell carcinoma (BCC) is the commonest skin cancer in Australia that is highly invasive. Surgical removal is its main treatment option but causes scarring and is impractical when there are multiple cancers. C-Jun, a molecule promoting cell growth is present in abnormally large amount in BCC compared to normal cells. Dz13 targets and destroys these molecules, killing cancer cells when injected into the tumour. Dz13 may hence become a more effective and aesthetic alternative of treating BCC.
The Role Of Patched/Hedgehog Signalling In Common Human Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Mutations in the patched -hedgehog pathway are responsible for most of the common skin cancer basal cell carcinoma and some of the brain tumour medulloblastoma. Despite this knowledge we still do not know which cell in the skin gives rise to the basal cell carcinoma, and which cell in the brain gives rise to medulloblastoma. This application describes an approach using animal models to answer these questions and therefore further our understanding of how a normal cell becomes a tumour cell. In a ....Mutations in the patched -hedgehog pathway are responsible for most of the common skin cancer basal cell carcinoma and some of the brain tumour medulloblastoma. Despite this knowledge we still do not know which cell in the skin gives rise to the basal cell carcinoma, and which cell in the brain gives rise to medulloblastoma. This application describes an approach using animal models to answer these questions and therefore further our understanding of how a normal cell becomes a tumour cell. In addition this proposal extends out current studies to examine new gene family members in large tumour collections.Read moreRead less
Regulation Of Hedgehog Signalling Through Intracellular Trafficking Events
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
The hedgehog signalling cascade plays a role in forming almost every organ of the body during development of an embryo. Perturbation of the function of key members of this pathway during embryonic development often results in death in utero or severe childhood abnormalities. In addition, disruption to this pathway also results in a range of cancers, most notably the extremely common skin cancer basal cell carcinoma. In this proposal we aim to investigate in detail the regulatory mechanisms which ....The hedgehog signalling cascade plays a role in forming almost every organ of the body during development of an embryo. Perturbation of the function of key members of this pathway during embryonic development often results in death in utero or severe childhood abnormalities. In addition, disruption to this pathway also results in a range of cancers, most notably the extremely common skin cancer basal cell carcinoma. In this proposal we aim to investigate in detail the regulatory mechanisms which operate to ensure that this complex pathway of interacting molecules functions correctly during embryonic development. By understanding how this regulation occurs we will gain valuable insight into how disruption of this pathway results in such a range of disease, as well as into how agents which modulate this pathway may potentially act in a therapeutic setting.Read moreRead less
Conditional Knockout Of The Murine Patched Gene For The Study Of Skin Differentiation And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$423,564.00
Summary
Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectiv ....Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectively removing patched gene function from specific cell of the skin. In doing this we will be able to determine the exact role of this gene in skin development, and how mutation causes common skin cancer.Read moreRead less