Genetic And Environmental Risk Factors For Colorectal Cancer: Anatomic Site Specificity
Funder
National Health and Medical Research Council
Funding Amount
$560,000.00
Summary
Cancer of the large bowel (colorectal cancer) is the second most common cancer in Australians and is becoming more common. Despite this, there is still much uncertainty about what causes some people to develop this cancer. We believe that some of this uncertainty arises because there are actually different causes of cancer for different sections of the colon and rectum. This study aims to collect information from 1000 people with colorectal cancer and 1000 people without colorectal cancer, and c ....Cancer of the large bowel (colorectal cancer) is the second most common cancer in Australians and is becoming more common. Despite this, there is still much uncertainty about what causes some people to develop this cancer. We believe that some of this uncertainty arises because there are actually different causes of cancer for different sections of the colon and rectum. This study aims to collect information from 1000 people with colorectal cancer and 1000 people without colorectal cancer, and compare various factors such as their genetic makeup, diet, AND lifestyle. We expect to find that some factors are more common in people with cancer in the upper parts of the bowel, while other factors are more common in people with cancer in the lower parts of the bowel. This kind of information can be used to design programs to prevent colorectal cancer. For example, we might advise people to exercise more or eat more fish in order to decrease their chances of developing this cancer.Read moreRead less
Risk And Prognostic Factors For Breast Cancer Of Different Immunohistochemical Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$294,461.00
Summary
Breast cancer is a heterogeneous disease. Gene expression analysis has identified a number of subtypes that are different with respect to pathology, prognosis, and response to treatment. Building on an existing cohort study, we aim to identify risk and prognostic factors for molecular subtypes of breast cancer.
Role Of Musculoskeletal Biomechanical Factors In Cartilage Loss In Those Who Undergo Partial Medial Menisectomy.
Funder
National Health and Medical Research Council
Funding Amount
$654,530.00
Summary
The novel outcomes from our project are that we will identify whether musculoskeletal-biomechanical factors that can be modified are associated with adverse cartilage changes in a subgroup of individuals with an increased risk of developing knee OA, those who have undergone an APM. The findings of this research are timely and of major international significance as there is increasing attention being paid to preventing OA rather than merely treating the signs and symptoms. Our state-of-the-art me ....The novel outcomes from our project are that we will identify whether musculoskeletal-biomechanical factors that can be modified are associated with adverse cartilage changes in a subgroup of individuals with an increased risk of developing knee OA, those who have undergone an APM. The findings of this research are timely and of major international significance as there is increasing attention being paid to preventing OA rather than merely treating the signs and symptoms. Our state-of-the-art measure of cartilage changes will allow us to detect those at risk much sooner than traditional measures using radiographs. The measures are also leading edge internationally. We chose these specific factors to investigate as there is evidence that they can be modified with appropriate interventions. For example, static joint alignment could be modified with foot orthoses [Crenshaw, 2000 #1016], muscle weakness can be addressed with strength programs and mechanical loading across the knee could be reduced via weight loss programs or techniques to alter gait patterns. Currently, formal supervised post-operative rehabilitation is not routinely prescribed following APM because it is considered a routine procedure. If our research identifies risk factors for increased cartilage loss then we will be able to develop appropriate intervention strategies for individuals following an APM. These interventions can then be formally tested as to their effectiveness in reducing adverse cartilage changes using randomised controlled trials. In particular, this could lead to changes in current post-operative clinical practice for this patient group. Ultimately, this could reduce the risk of OA in the future and the resultant personal and societal costs of this condition.Read moreRead less
Molecular Regulation Of CRH Gene Expression In The Human Placenta
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormon ....Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely the rise in CRH production occurs earlier and more rapidly, while in women who deliver late the rise occurs more slowly. This work has led to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done by examining the DNA sequences involved in controlling the CRH gene and by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and preterm birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be developed.Read moreRead less
Epithelial - Stromal Interactions In Pancreatic Cancer: Role Of Pancreatic Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$425,750.00
Summary
The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for ....The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for novel approaches to this lethal disease. The proposed project involves an examination of the local tissue reaction around pancreatic cancer. This tissue reaction is usually prominent and the cells involved may determine the extent of local and distant spread of the cancer. Modulation of this tissue reaction may limit pancreatic cancer growth and thus improve outcome.Read moreRead less
Expression And Role Of Integrins During Lens Development And Cataractogenesis
Funder
National Health and Medical Research Council
Funding Amount
$336,760.00
Summary
Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous rese ....Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous research, which has identified molecules (growth factors) that are involved in either the regulation of normal lens development and growth (FGF and TGF-beta) or the induction of cataractous changes in the lens epithelium (TGF-beta). The studies are directed at identifying members of an important family of cell adhesion molecules, the integrins, in the lens and examining the role that these molecules play in controlling lens structure and function. These cell surface glycoproteins function in adhesion of cells to each other and to extracellular matrix, and transmit signals in response to changes in the extracellular environment. Such responses include cell proliferation, migration and differentiation. In this regard they often act in concert with growth factor receptors (eg. FGF and TGF-beta). After defining where and when integrins are expressed in the developing lens we will investigate their function in mediating various lens cell responses by using genetic manipulations to alter the expression of integrins or their intracellular signaling mediators in lenses of transgenic mice. In addition, a lens explant culture system will be used to investigate the roles integrins play during lens development and during formation of anterior subcapsular cataract by TGF-beta. These studies will provide important insights into the molecular mechanisms that control cellular events in normal and abnormal lens development.Read moreRead less
Adult Consequences Of Childhood Exposure To Psychological Trauma
Funder
National Health and Medical Research Council
Funding Amount
$292,530.00
Summary
The importance of childhood experience to adult adjustment (DOES THIS MAKE SENSE) is an issue of general public health interest. In particular, in the area of personality development, there are a number of theories concerning the importance of childhood experience and developmental stresses on later personality, development, psychological functioning and physical health. More recently there has been debate on the accuracy with which adults areable to remember traumatic experiences in childhood. ....The importance of childhood experience to adult adjustment (DOES THIS MAKE SENSE) is an issue of general public health interest. In particular, in the area of personality development, there are a number of theories concerning the importance of childhood experience and developmental stresses on later personality, development, psychological functioning and physical health. More recently there has been debate on the accuracy with which adults areable to remember traumatic experiences in childhood. This study will follow a group of 808 primary school children who were exposed to the 1983 Ash Wednesday bushfires in SOuth Australia. They were involved in a study which examined them two months, eight months and twenty six months after the disaster. This rich descriptive set of information about these children and their families forms an objective data base against which their adult recall of the experience can be judged. The symptoms of these children were also documented at the time as was their disaster exposure. The impact of this one event, in the context of the other developmental influences will be examined as determinants of their adjustment in adult life. Finally, there has been an increasing interest in the way that previous traumatic exposure influences the nature of the hormonal response to stress. Using a test of functioning of the cortisol system, the stress response of this population will be compared with a control population who were also studied at the time of the original disaster.Read moreRead less
The Beyondblue Schools Research Initiative: A Two-year Follow-up.
Funder
National Health and Medical Research Council
Funding Amount
$827,285.00
Summary
The prevalence of Depressive Disorders among children and adolescents was estimated in the Australian National Child and Adolescent Mental Health Survey to be 3.7%. This means that at any single point of time, approximately 138,000 Australian children and adolescents are experiencing a Depressive Disorder. Furthermore, the National Survey found that less than half (46%) of those with a Depressive Disorder received any help over a 6 month period prior to the survey, with only 8% attending a menta ....The prevalence of Depressive Disorders among children and adolescents was estimated in the Australian National Child and Adolescent Mental Health Survey to be 3.7%. This means that at any single point of time, approximately 138,000 Australian children and adolescents are experiencing a Depressive Disorder. Furthermore, the National Survey found that less than half (46%) of those with a Depressive Disorder received any help over a 6 month period prior to the survey, with only 8% attending a mental health clinic, and only 4% attending a hospital-based Department of Psychiatry. These findings emphasise the importance of finding alternative approaches to help the large number of young people with depression who do not receive help from professional services. This application seeks funding to evaluate the beyondblue Schools Research Initiative. The key features of the initiative are the development of a strong partnership between the health and education sectors and a focus on both individual-level and school-level risk factors. This has enabled us to provide a much longer duration of intervention than previous studies, to test the intervention in several different Australian States, and to utilise a broadly based intervention that includes a range of approaches, each of which have the potential to help reduce adolescent depression. The significance of the project lies in its potential to identify effective interventions which can reduce rates of depression experienced by adolescents, and the quality of the ongoing research partnership we have established across the education and health sectors. We anticipate that this partnership will be utilised for ongoing research in this area.Read moreRead less
The Epidemiology Of Staphylococcus Aureus And Antibiotic Resistance In Community-acquired Infections
Funder
National Health and Medical Research Council
Funding Amount
$1,267,784.00
Summary
Staphylococcus aureus infections range from boils to life-threatening diseases and are increasingly resistant to antibiotics and difficult to treat. This study follows patients with community-acquired S. aureus infections, and close contacts, for 24 months to see if they carry S. aureus (nose swabs) or develop infection. Our data on risk factors for colonisation and infection will help doctors decide whether to trace and treat contacts of patients to protect households from further infection.