The Role Of Src Family Tyrosine Kinases In Inflammatory Lung Disease And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
We aim to learn why some people develop COPD, a serious lung disease, and adenocarcinoma, a common fatal lung cancer. COPD is mostly caused by cigarette smoke which induces lung inflammation. Lung inflammation, which involves macrophage activation, is a major cancer risk. Macrophages can destroy lung tissue, and they may promote cancer development. We will study the role of Src kinases, which can regulate macrophage activation, which may lead to new treatments for these diseases.
The Scientific Basis For The Integration Of Surgery And Immunotherapy For Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$516,394.00
Summary
The work in this grant focuses on the effects of cancer surgery (tumor resection and removal of lymph nodes) on the anti-cancer immune response. It also examines whether delivery of agents into the residual tumour bed following surgery can effectively boost the effects of surgery on the immune system. The results obtained will help guide the rational design of future combination surgery-immunotherapy treatment regimens.
The Role Of Glucocorticoids, Retinol And CAMP Signaling In Lung Development And Neonatal Respiratory Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$447,000.00
Summary
Underdeveloped lungs at birth and adult lung diseases (ie emphysema, acute resipratory distress, and asthma) are a major cause of hopitalization and death. The World Health Organization ranks resipratory diseases at number 6 in the global burden of disease. Preterm birth with associated respiratory complications occurs in about 10% of all human births and accounts for 75% of neonatal deaths not associated with congenital abnormalities . Respiratory Distress Syndrome (RDS) is a major complication ....Underdeveloped lungs at birth and adult lung diseases (ie emphysema, acute resipratory distress, and asthma) are a major cause of hopitalization and death. The World Health Organization ranks resipratory diseases at number 6 in the global burden of disease. Preterm birth with associated respiratory complications occurs in about 10% of all human births and accounts for 75% of neonatal deaths not associated with congenital abnormalities . Respiratory Distress Syndrome (RDS) is a major complication in preterm births and the routine antenatal treatment of glucocorticoids has a major benefit in reducing incidence of RDS leading to decreased neonatal mortality. Glucocorticoids improve lung maturation yet their exact detailed role is not fully understood. Other systemic hormones and factors , such as vitamin A (precursor for retinoic acid) are also important in regulating, completing and maintaining proper lung development and function. Vitamin A deficiency alters lung structure and function, and is believed to be a causal factor in chronic lung diseases such as bronchopulmonary dysplasia, frequently problematic to infants. Detailed understanding of how these hormones work in the lung is critical to the future improvement of treatments for respiratory distress at birth and other respiratory conditions (emphysema, asthma) during adult life. We have developed a number of mouse models to study how these hormones work in the lung and allows us to perform investigations not possible in the human system. Using these mouse models of hormone resistance for glucocorticoids, retinoic acid (vitamin A) and cAMP signaling we will study in detail how these hormones work in the developing lung. Outcomes will be detailed knowledge and mechanisms of action that are critical for the design and testing of novel agents and therapies for immature lungs at birth and in adult lung dysfunction and diseaseRead moreRead less
DEFINING SUBPOPULATIONS OF PATHOGENIC MACROPHAGES UNDERLYING LUNG DISEASES
Funder
National Health and Medical Research Council
Funding Amount
$640,496.00
Summary
Chronic obstructive pulmonary disease (COPD) is a serious lung disease that afflicts over 1 million people in Australia and adenocarcinoma is a common fatal lung cancer; both are typically caused by cigarette smoking, and macrophage-rich inflammation is a hallmark feature. Macrophages can destroy lung tissue and promote cancer development. Herein we will identify and profile macrophage subpopulations that are associated with lung inflammation and cancer to identify therapeutic targets that may y ....Chronic obstructive pulmonary disease (COPD) is a serious lung disease that afflicts over 1 million people in Australia and adenocarcinoma is a common fatal lung cancer; both are typically caused by cigarette smoking, and macrophage-rich inflammation is a hallmark feature. Macrophages can destroy lung tissue and promote cancer development. Herein we will identify and profile macrophage subpopulations that are associated with lung inflammation and cancer to identify therapeutic targets that may yield novel intervention strategies.Read moreRead less
Early Life Arsenic Exposure Alters Lung Development And Inflammatory Responses To Virus And Cigarette Smoke
Funder
National Health and Medical Research Council
Funding Amount
$455,380.00
Summary
The contamination of drinking water sources with arsenic is a global health issue affecting millions. While arsenic is a well known cancer causing agent, recent evidence suggests that early life arsenic exposure via drinking water increases the risk of obstructive lung disease in later life. This project aims to examine how the timing and dose of arsenic exposure influences lung development and the response to respiratory insults including viral infection and cigarette smoke.
Low-yield Cigarettes And Diminution Of Small Airways Lung Function In Long-term Smokers
Funder
National Health and Medical Research Council
Funding Amount
$209,500.00
Summary
The modern cigarette has been designed to produce low yields of tar when the tobacco in the cigarette is burnt. The tar contains human carcinogens, and monitoring and regulating yields of tar has long been part of the comprehensive tobacco control strategy in Australia. This focus on tar has given an implicit endorsement of the low-yield cigarette as a safer cigarette. Recently, however, controversy has emerged about whether smoking low-yield cigarettes has reduced the harm done by smoking. The ....The modern cigarette has been designed to produce low yields of tar when the tobacco in the cigarette is burnt. The tar contains human carcinogens, and monitoring and regulating yields of tar has long been part of the comprehensive tobacco control strategy in Australia. This focus on tar has given an implicit endorsement of the low-yield cigarette as a safer cigarette. Recently, however, controversy has emerged about whether smoking low-yield cigarettes has reduced the harm done by smoking. The concern is that adenocarcinoma of the lung, a type of lung cancer that is most common in the small peripheral airways, has increased in frequency. This could be because the low-yield cigarette, with reduced yields of nicotine as well as tar, is smoked more intensely by smokers to compensate for the low nicotine. By smoking more intensely, we mean taking larger and more frequent puffs, inhaling the smoke deeply into the lungs, and holding the breath before expiring. This method of smoking would result in more tar particles being deposited in the peripheries of the lung where adenocarcinoma is most common. Because cigarette smoking has been linked also with other structural changes in the small airways of the lung, resulting in obstruction of airflow, we will test whether smoking low-yield cigarettes is associated with greater obstruction of the small airways than is smoking higher-yield cigarettes. To test whether the mechanism is the method of smoking, we will carefully describe and quantify each subject's pattern of smoking including the deposition of smoke-like Technegas particles in the peripheral lung.Read moreRead less
Asbestos And Related Diseases In Western Australia
Funder
National Health and Medical Research Council
Funding Amount
$404,727.00
Summary
This project will extend the follow-up of large, well established groups of people who have experienced significant exposure to blue asbestos, either through their jobs or environmentally. Mesothelioma, lung cancer and asbestosis are common among these groups. This study will provide information on the effects of different levels of exposure to blue asbestos. Ways in which these diseases may be prevented through the diet and other lifestyle habits will be closely examined. This project provides ....This project will extend the follow-up of large, well established groups of people who have experienced significant exposure to blue asbestos, either through their jobs or environmentally. Mesothelioma, lung cancer and asbestosis are common among these groups. This study will provide information on the effects of different levels of exposure to blue asbestos. Ways in which these diseases may be prevented through the diet and other lifestyle habits will be closely examined. This project provides important data on the dose-response effects of a known carcinogen. Due to the integrated nature of our already established follow up systems we are in a unique position worldwide to achieve these aims. The dose response relationships between exposure and disease identified by this study will contribute to occupational health and safety exposure standards and compensation policy in Australia. The information on lifestyle factors is appropriate for use in many different health promotion interventions. Ongoing contact with the cohorts is critical to our involvement in collaborative preventative and biological studies.Read moreRead less
Role Of Amnion Derived Stem Cells In Reducing Lung Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$349,485.00
Summary
Human amniotic epithelial multipotential cells from the term placenta are being studied in a mouse model of pulmonary fibrosis-emphysema to demonstrate their anti-inflammatory, anti-fibrotic, immune-suppresive and lung repair capability. The availability and numbers of these cells from discarded placentas at birth are unlimited and their potential to repair serious lung disease would have strong clinical interest as a new stem cell therapy.
Asthma, Lung Function, Snoring And Passive Smoking In Busselton
Funder
National Health and Medical Research Council
Funding Amount
$115,110.00
Summary
Respiratory diseases such as asthma, chronic obstructive airway disease, and sleep apnoea are common in the community, and asthma is becoming more and more common. These diseases are a major cause of morbidity, lost time from work, use of health and community resources and death. Using information collected by the Busselton Health Studies between 1966 and 2000, we will investigate some new epidemiological aspects of respiratory diseases. Some of the questions we will examine are: * How much more ....Respiratory diseases such as asthma, chronic obstructive airway disease, and sleep apnoea are common in the community, and asthma is becoming more and more common. These diseases are a major cause of morbidity, lost time from work, use of health and community resources and death. Using information collected by the Busselton Health Studies between 1966 and 2000, we will investigate some new epidemiological aspects of respiratory diseases. Some of the questions we will examine are: * How much more common has asthma become in the Busselton population? Has the increase been more pronounced in some groups than in others (eg younger people)? Have other respiratory diseases also become more common? * Is decline in FEV1 over time a more useful measure of lung health than a single FEV1 measurement? How is decline in FEV1 related to age and other factors such as asthma, smoking, chronic respiratory diseases and hay fever? * Do the following put people at increased risk of sleep apnoea: overweight, recent weight gain, smoking, heavy alcohol intake, respiratory illness, cardiovascular disease and use of sedatives? * Do non-smoking spouses of smokers suffer more respiratory illness than spouses of non-smokers? We expect that results from this study will increase our understanding of the causes and progression of respiratory diseases, and may eventually point to ways of reducing the burden of these diseases in the community. Since all the information needed has already been collected in the course of earlier health surveys, this study will be particularly cost-effective.Read moreRead less