Molecular Determinants Of Advanced Disease In Ovarian Granulosa Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$612,244.00
Summary
Granulosa cell tumours of the ovary (GCT) represent 5-10% of malignant ovarian cancers. They are distinct from the more common epithelial tumours and although considered to have a much better prognosis, they have a propensity to late recurrence. Recurrent or aggressive GCT have a poor prognosis. These studies will investigate the molecular basis of recurrence and aggressive behaviour in GCT. This will provide both prognostic information and also potential therapeutic targets.
Insights Into The Acute Cerebral Lesion Of Childhood Diabetes And It's Neuropsychological Sequelae
Funder
National Health and Medical Research Council
Funding Amount
$416,000.00
Summary
Type 1 diabetes in childhood is a major cause of morbidity with an Australian prevalence of approximately 20 per 100,000 children under 15 years of age. The leading cause of death in type 1 diabetes in children and adolescents is diabetic ketoacidosis complicated by cerebral oedema (brain swelling), the origins of which remain unknown. This research is aimed at providing an insight into changes in the brain of children with diabetic ketoacidosis (DKA) and the relationship of these brain changes ....Type 1 diabetes in childhood is a major cause of morbidity with an Australian prevalence of approximately 20 per 100,000 children under 15 years of age. The leading cause of death in type 1 diabetes in children and adolescents is diabetic ketoacidosis complicated by cerebral oedema (brain swelling), the origins of which remain unknown. This research is aimed at providing an insight into changes in the brain of children with diabetic ketoacidosis (DKA) and the relationship of these brain changes to short and long term neuropsychological functioning. The major aim of this project is to provide an insight into brain changes of children with diabetic ketoacidosis (DKA) and the relationship of these brain changes to subseuqent brain function. This is a study where we will simply observe differences between newly diagnosed type 1 diabetic patients with no ktoacidosis, ketoacidosis or ketoacidosis with brain swelling over 6 months. We will measure brain function using various techniques includiung: magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), electrophysiology (EEG) and neuropsychological tests. The significance of this project is that it will provide insight into the brain impairment of diabetic patients with and without DKA, and with brain swelling in the context of DKA. By further clarifying the nature of brain impairment we will provide early intervention strategies to improve psychological development of the young patients with diabetes. In addition to this we hope to better understand the origins of brain swelling during DKA and design treatment protocols that will prevent this devastating complication.Read moreRead less
Type 2 diabetes represents an escalating global health problem. In Australia 7.2% of the population has diabetes but an additional 16% have difficulty handling glucose, a problem which frequently precedes the development of diabetes. Resistance of tissues to the action of insulin is an essential pre-requisite for type 2 diabetes but is also closely associated with the syndrome of obesity, dyslipidaemia, hypertension and cardiovascular diseases (Syndrome X). Genetic factors combined with a high c ....Type 2 diabetes represents an escalating global health problem. In Australia 7.2% of the population has diabetes but an additional 16% have difficulty handling glucose, a problem which frequently precedes the development of diabetes. Resistance of tissues to the action of insulin is an essential pre-requisite for type 2 diabetes but is also closely associated with the syndrome of obesity, dyslipidaemia, hypertension and cardiovascular diseases (Syndrome X). Genetic factors combined with a high caloric intake and a sedentary lifestyle are together responsible for the development of insulin resistance. From evidence that we and others have obtained in recent years it is evident that an important mediator of insulin resistance is the amount of fat which accumulates in muscle and liver. One way in which this abnormality seems to cause insulin resistance is through interference with the normal signalling mechanism which causes increased glucose metabolism in response to insulin. While experiments in cell systems have identified some candidate molecules that may be involved, a need exists to demonstrate whether their dysregulation actually causes the insulin resistance in the whole animal or human, or are merely associated with it. We will use novel techniques to manipulate the levels of one of these candidate genes, protein kinase B-Akt, and its regulators in the muscle of rodents. We will then examine the effects of these manipulations on insulin resistance using a combination of metabolic and molecular tests. Building upon earlier work we will also determine how important different subtypes of this molecule are for both normal and abnormal insulin-glucose metabolism, and whether these molecules or others in the pathway are more important in insulin resistance. This knowledge will be invaluable in tailoring specific novel treatment strategies or drugs for prevention or treatment of insulin resistance, and thus reducing the burden of type 2 diabetes and Syndrome X.Read moreRead less
Insulin-like Growth Factor Binding Protein-2 Is A Crucial Activator Of Aggressive Behaviour In Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
The insulin-like growth factor (IGF) system, required for normal development and adult life, is often altered in many diseases including cancer. Key regulators of the IGF system are the IGF binding protein (IGFBP) of which IGFBP-2 is the 2nd most abundant. IGFBP-2 may enhance or inhibit the IGFs, but the mechanisms are not clear. This proposal aims to dissect IGFBP-2 action with the ultimate goal to provide knowledge for the development of targeted therapeutic modulators of IGFBP-2 activity.