The Role Of CXCL12 (SDF-1)/CXCR4 In Pathological Angiogenesis And Osteolytic Bone Disease In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$665,896.00
Summary
Multiple myeloma (MM) is the second most common haematological (or blood) cancer in western countries and is unique amongst blood cancers in its capacity to destroy the skeleton. MM is a cancer of plasma cells, which in their normal non-cancerous form, reside in lymph nodes and produce antibodies against infectious agents. When they become cancerous, they migrate or home to congenial sites within the bone marrow (BM). This directed movement or homing occurs under the influence of a chemokine mol ....Multiple myeloma (MM) is the second most common haematological (or blood) cancer in western countries and is unique amongst blood cancers in its capacity to destroy the skeleton. MM is a cancer of plasma cells, which in their normal non-cancerous form, reside in lymph nodes and produce antibodies against infectious agents. When they become cancerous, they migrate or home to congenial sites within the bone marrow (BM). This directed movement or homing occurs under the influence of a chemokine molecule called CXCL12 which acts as a calling card for plasma cells to leave the lymph node and migrate to the BM. Once within the BM, the cells rapidly grow in response to BM-derived growth factors. This rapid growth causes a depletion in oxygen availability within the tumour and it becomes hypoxic. In response to this hypoxia, the tumour expresses a gene called hypoxia-inducible factor-1 (HIF-1) which regulates the expression of many proteins, including the chemokine CXCL12. Our studies show that the abnormal expression of CXCL12 by the plasma cells acts to promote blood vessel formation within the tumour, which in turn leads to greater tumour growth. In addition, our studies suggest that abnormal CXCL12 expression also promotes the recruitment and activation of large numbers of osteoclast (OC) precursors form the peripheral blood. OC are cells which normally remove unwanted or damaged bone. This proposal will study the interplay between HIF and CXCL12 in the establishment and development of MM and the associated bone destruction.Read moreRead less
Preparing Australia For Genomic Medicine: A Proposal By The Australian Genomics Health Alliance
Funder
National Health and Medical Research Council
Funding Amount
$25,000,000.00
Summary
The sequencing of the human genome brings the possibility of more accurate identification of the underlying basis of many diseases. This technology has moved so rapidly, however, that clinical access has been limited. In this application, a national alliance of clinicians, researchers, health economists and policymakers will evaluate the case for clinical genomics across inherited disease and cancer, determine how best to deliver this to the patient and train a capable workforce.
Electrophysiologic Phenotyping Of Non Ischaemic Cardiomyopathy To Predict Clinical Outcome
Funder
National Health and Medical Research Council
Funding Amount
$374,676.00
Summary
Non-ischemic cardiomyopathy (NICM) is a common cause of heart failure and sudden death. Currently, the guidelines for the management are generalised and do not differentiate patients at high risk of disease progression and sudden death. This project aims to identify the electrical and structural properties of heart, to predict the clinical course in patients with NICM. Identification of high-risk patients will help allocate resources wisely and enable appropriate patient counselling.
Blood Protein Biomarkers For Frontotemporal Lobar Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$184,305.00
Summary
This project will assess blood proteins as biomarkers for different pathogenic forms of frontotemporal dementia (FTD), one of the major neurodegenerative dementias with a very rapid disease progression (mean survival 3 years). At present, it is not possible to predict which pathological variant is present in any given patient. We plan to develop blood protein biomarker assays capable of diagnosing the pathology in vivo.
Study Of C-KIT Mutations In Familial Gastrointestinal Stromal Tumours, Melanoma And A Novel Form Of Waardenburg Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$68,378.00
Summary
The primary aim of this research project is to study mutations in a cancer causing gene called c-KIT. We seek to identify tumour characteristics which are predictive for the presence of particular types of c-KIT mutations in melanomas and gastrointestinal stromal tumours. The detection of tumours harbouring these mutations will help in the treatment of cancer sufferers because this group of patients have been shown to respond very well to a class of drugs known as tyrosine kinase inhibitors.
SNAC2: A Randomised Trial Of Extending Sentinel Node Based Management To Women With Larger Or Multifocal Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,266,430.00
Summary
SNAC2 extends the work begun in SNAC1, which recruited 1,088 women over 4 years. SNAC1 will determine if sentinel node biopsy causes less arm problems than axillary clearance. The goal of SNAC2 is to establish the risk of local recurrence and long term safety of sentinel node biopsy, especially for women with larger or multiple tumours. SNAC2 is needed to determine whether the smaller operation gives cure rates as good as axillary clearance. If it does, then it will become standard practice.