Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. A certain change (called methylation) affects some g ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. A certain change (called methylation) affects some genes in the lungs, but it is not yet known how common this change is or how it affects smokers and people who have developed lung cancer. We will collect blood and sputum specimens from lung cancer patients to test to see if methylation is present, and also specimens from when patients have a routine bronchoscopy as part of their initial tests. If they have an operation for lung cancer, then the part of the lung that is removed and not needed for diagnosis will also be tested for methylation. In this study, we will study whether methylation is an accurate test for lung cancer, whether it is present in parts of the lung near from the lung cancer, and whether it predicts better or worse results after treatment. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Identifying The Targets Of MiRNA Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$290,600.00
Summary
microRNAs are noncoding RNAs with fundamental functions in biology and significant roles disease. microRNAs control gene expression by destroying RNA or controlling its translation into cellular proteins. To determine how certain microRNAs cause human disease it is essential to know their RNA targets. We are developing methods to identify these targets and aim to apply these methods to identify the targets of microRNAs with known roles in cancer.
Strategies To Enhance CD4 T Cell-mediated Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
The immune system is capable of controlling cancer, but frequently does not do so. In this project we will study two factors that compromise anti-cancer immune responses: regulatory T cells, which suppress immune responses, and tolerogenic dendritic cells, which subvert potentially beneficial responses to tumours. By manipulating these factors, we hope to enhance the effectiveness of the immune response against cancer.
Interactions Between Hedgehog And Ras Signaling In Lung Adenocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
Lung cancer is a common and lethal disease in our community. In this project, we explore how signaling pathways that regulate the development of the lung in embryos contribute to the initation and progression of lung cancer. To do this, we use a mouse model of lung cancer in which we can activate embryonic signaling pathways in adult mice to study there effect on the disease. Understanding these pathways will help us to better treat and prevent lung cancer in humans.
The migration of cancer cells (metastasis) is responsible for most cancer deaths. Central to this is dynamic organisation of the actin cytoskeleton _ an internal structure that provides cell shape and enables movement. We have identified a family of small molecules (called miR-200) that regulates this actin cytoskeleton through specifically downregulating various genes. We are investigating the nature of these genes and their role in cell motility _ an underlying pre-requisite of metastasis.
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
The Transcriptional Profile Of A Metastatic Circulating Melanoma Cell
Funder
National Health and Medical Research Council
Funding Amount
$273,630.00
Summary
Melanoma is an aggressive skin cancer, and the leading cause of skin cancer related deaths. Disease spread is difficult to detect and difficult to cure. We previously identified circulating melanoma cells in patient peripheral blood and showed that their presence is associated with disease stage and recurrence. We will now fully characterise the phenotype of actively metastatic circulating melanoma cells for better patient prognosis and routine monitoring.
The Role Of The Cytokine Receptor Gp130 In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Prostate cancer is a leading cause of cancer deaths in men in the Western world. Neuroendocrine cells may play an important role in the development of these cancers, but their biology is essentially uncharacterized. Activation of the cell-bound protein gp130 results in neuroendocrine differentiation, growth and chemotherapeutic drug resistance of prostate cancer cells. We will use gp130-dependent differentiation to understand how neuroendocrine cells influence normal and cancerous prostate cells ....Prostate cancer is a leading cause of cancer deaths in men in the Western world. Neuroendocrine cells may play an important role in the development of these cancers, but their biology is essentially uncharacterized. Activation of the cell-bound protein gp130 results in neuroendocrine differentiation, growth and chemotherapeutic drug resistance of prostate cancer cells. We will use gp130-dependent differentiation to understand how neuroendocrine cells influence normal and cancerous prostate cells, and to identify neuroendocrine-cell specific genes that may be of diagnostic or therapeutic benefit in prostate cancer. Gp130 can be activated by a group of hormones called the interleukin-6 type cytokines in the presence of certain cell-bound proteins (receptors). If these receptors are inappropriately expressed in the prostate, inappropriate activation of gp130 could occur resulting in prostate cancer cell growth or neuroendocrine differentiation. If we can determine that these receptors are expressed in prostate cancer, but not in non-cancerous prostate, this would have diagnostic or therapeutic benefit.Read moreRead less
Sympathetic Nervous System Regulation Of The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$396,212.00
Summary
Metastasis is the major cause of morbidity and mortality in breast cancer. These studies will evaluate the translational opportunity of targeting the sympathetic nervous system as a common regulator of cancer progression pathways. By exploiting sensitive imaging technology for non-invasive, real-time assessment of stress biology, these studies will define the neuroendocrine mechanisms that operate in the tumour microenvironment to support dissemination and arrest of cancer cells in target organs ....Metastasis is the major cause of morbidity and mortality in breast cancer. These studies will evaluate the translational opportunity of targeting the sympathetic nervous system as a common regulator of cancer progression pathways. By exploiting sensitive imaging technology for non-invasive, real-time assessment of stress biology, these studies will define the neuroendocrine mechanisms that operate in the tumour microenvironment to support dissemination and arrest of cancer cells in target organs.Read moreRead less