Validation Of Stat3 As A Therapeutic Target In Diseases Arising From Its Inappropriate Activation By Gp130 Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$674,142.00
Summary
Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach lining cells. We will employ a number of strategies to establish molecularly the exte ....Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach lining cells. We will employ a number of strategies to establish molecularly the extent to which this mouse model is informative for gastric cancer inhuman. In aprticular we will identify the genes that are involved in the progression of the disease. One important focus of the project is to see whether or not the moelcule (called Stat3) whose aberrant activation triggers the disease in the mouse could provide a future pharmacological target for intervention with the disease. Similarly with expertise of CIB, we will investigate with novel proteomics techniques whther we can identify a protein in the serum of these mice, which could give us aclue of whether or not the mouse ahs already developed disease. Such a protein could be of potentail diagnostic importance in the future to screen human for gastric cancer which in its eraly stages is usually without any clinical symptoms. In a related Aim we will find out the gene that can genetically cooperate with Stat3 and that is required to enable survival of newborn mice. It may well turn out mOur proposal combines the expertise of the two investigators in signal transduction and that this gene may be an important determinant to ensure that Stat3 triggers physiological rather than pathological responses in many differnet organs.Read moreRead less
Molecular And Genotypic Risk Factors For Abdominal Aortic Aneurysms
Funder
National Health and Medical Research Council
Funding Amount
$221,750.00
Summary
An Abdominal Aortic Aneurysms (AAA) is a dilatation of the main abdominal artery. This is an asymptomatic condition which may cause sudden death due to rupture of the AAA once it reaches a certain size (usually over 5cm in diameter) Between 1996 and 1998, 12,000 men aged 65-79 attended the Western Australian Abdominal Aortic Aneurysm screening study. The main aim of the study is to assess the influence of screening on mortality from AAA. Since 1997, approximately 90 men with large AAA have had e ....An Abdominal Aortic Aneurysms (AAA) is a dilatation of the main abdominal artery. This is an asymptomatic condition which may cause sudden death due to rupture of the AAA once it reaches a certain size (usually over 5cm in diameter) Between 1996 and 1998, 12,000 men aged 65-79 attended the Western Australian Abdominal Aortic Aneurysm screening study. The main aim of the study is to assess the influence of screening on mortality from AAA. Since 1997, approximately 90 men with large AAA have had elective surgical repair of AAA and 700 men with small AAA (aortic diameter 3-5 cm) have participated in the follow-up study involving 6-12 monthly ultrasound scans. The aim of the follow-up study is to assess rates of and risk factors for expansion of screen-detected AAA. The cause of AAA is unclear but appears to be due to a combination of environmental (eg smoking) and genetic influences. It is unknowm which genes might be involved. The current grant application seeks funding to initiate the study of possible genes associated with AAA . Blood samples from which DNA (genetic material) can be extracted have already been obtained from 650 men with AAA. Men without AAA are currently being reviewed as part of another study and it will be possible to obtain similar DNA samples these men. Patterns of gene polymorphisms (common minor mutations) in men with AAA will be compared with those without AAA.Read moreRead less
Factors Regulating Initiation, Progression And Submucosal Invasion In Gastric Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
Gastric cancer is the second most common cause of death in humans. It is strongly associated with Helicobacter pylori, a common and easily transmitted bacterium which infects about half the world's population. Exactly how Helicobacter pylori (HP) causes cancer, and why it does so in only a small percentage of those infected is unknown. It is clear however that Helicobacter species that produce a strong inflammatory response in the host and possess a full complement of pathogenic (disease-associa ....Gastric cancer is the second most common cause of death in humans. It is strongly associated with Helicobacter pylori, a common and easily transmitted bacterium which infects about half the world's population. Exactly how Helicobacter pylori (HP) causes cancer, and why it does so in only a small percentage of those infected is unknown. It is clear however that Helicobacter species that produce a strong inflammatory response in the host and possess a full complement of pathogenic (disease-associated) genes are more strongly associated with cancer development after long-term infection than others. We have recently developed a genetically modified mouse which has a minor defect in a regulatory pathway which controls some aspects of gut inflammation. Surprisingly 100% of these mice rapidly develop gastric cancer which has many similarities with the human disease, including inflammation, loss of structure of the stomach lining and penetration of cancerous cells into the muscle layers below. The objectives of this project are to work out whether HP induces similar changes in normal stomach cells as occurs in our defined mouse model of gastric cancer. Specifically we will determine if HP disturbs the way a particular mediator of inflammation works, and if so the way this impacts on certain stomach genes which detect cancerous cells and prevent tumor growth.Read moreRead less