Characterisation Of Precursor Lesions In Colorectal Cancers With DNA Instability
Funder
National Health and Medical Research Council
Funding Amount
$60,190.00
Summary
It is now generally accepted that most colorectal cancers arise from previously benign lesions in the mucosal lining of the large bowel. These lesions are called adenomatous polyps. They have been extensively studied as have the cancers which evolve from them with regard to the type of cancer causing genetic changes they bear. Recently, it has been found that colorectal cancer is not a single disease in that there exists a subgroup comprising 15% of colorectal cancers which is an entirely differ ....It is now generally accepted that most colorectal cancers arise from previously benign lesions in the mucosal lining of the large bowel. These lesions are called adenomatous polyps. They have been extensively studied as have the cancers which evolve from them with regard to the type of cancer causing genetic changes they bear. Recently, it has been found that colorectal cancer is not a single disease in that there exists a subgroup comprising 15% of colorectal cancers which is an entirely different type wwith respect to genetic changes and biological behaviour. This subgroup contains cancers with a high level of microsatellite instability (MSI-high) and the cancers which comprise this group show none of the common genetic changes which can be demonstrated in both adenomatous polyps and the 85% of colon cancers which develop from them. The MSI-high colorectal cancers do however share some striking similarities to a type of polyp (hyperplastic) which has until quite recently been considered of little consequence. Our research group and others have shown an association with colorectal cancer in those patients in whom hyperplastic polyps are unusually large or numerous, especially if present in the right side of the large bowel, where the bulk of MSI-high colorectal cancers arise. The current proposal will investigate the hyperplastic polyp as a precursor lesion in the genesis of MSI-high cancers.Read moreRead less
Therapeutic Targeting Of The Hedgehog Signaling Pathway In Premalignant Lesions Of The Breast.
Funder
National Health and Medical Research Council
Funding Amount
$115,980.00
Summary
Breast screening has been successful in reducing deaths from breast cancer. Unfortunately it also detects increasing numbers of precancerous changes. Treatment of these changes is often aggressive, using surgery and radiotherapy. However we are unable to predict exactly which of the changes we need to treat. We aim to better understand the changes involved in this progression and try to block them using new drugs.
What Factors Affect Lesion Distribution In Multiple Sclerosis And Experimental Autoimmune Encephalomyelitis?
Funder
National Health and Medical Research Council
Funding Amount
$56,797.00
Summary
Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be m ....Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be much more susceptible to this attack than others, and the question that this study will address is why do lesions occur where they do in MS? Some preliminary results strongly suggest that there is a link between carrying particular genes that control immune responses, having immune cells that can attack one particular protein in the nervous system called PLP, and developing lesions in parts of the brain that control balance. This will be investigated further, and we will also look for other links between immune cells that can attack other proteins and development of lesions in particular areas. If such links can be identified, they would be very important for improved diagnosis of MS and it would enable more specific treatments for MS to be developed. We will also use experimental models of MS to investigate the exact components within the nervous system and within the immune system that play a role in directing the attack to particular sites.Read moreRead less
Identification And Molecular Characterisation Of High-risk Premalignant Breast Lesions
Funder
National Health and Medical Research Council
Funding Amount
$560,382.00
Summary
Understanding the full repertoire of genetic events that underlie the development of breast cancer may allow development of prevention strategies. This study will analyse genetic data of benign breast lesions that may be non-obligate precursors of breast cancer. Importantly, clinical management of these lesions is difficult. A reliable method of predicting the risk of progression to cancer would be a significant advance, with benefits to individual patients and also the health system.
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.