Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak protein is a member of the Bcl-2 family of apoptosis regulators, and plays a pivotal role in mediating cell death. By defining each step in Bak-mediated apoptosis, we aim to better understand how cancer cells accumulate, and how targeting the Bcl-2 family may lead to effective anti-cancer therapeutics.
Role Of Bak And Bax Membrane Anchors In Targeting And Apoptotic Pore Formation.
Funder
National Health and Medical Research Council
Funding Amount
$352,319.00
Summary
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak and Bax proteins are members of the Bcl-2 family of apoptosis regulators, and play a pivotal role in mediating cell death. By defining how these proteins form a pore in mitochondria, the point of no return in cell death, will help the development of novel anti-cancer agents that target the Bcl-2 family in general, and Bak and Bax in particular.
Immunising Aboriginal Mothers With Pneumococcal Polysaccharide Vaccine To Prevent Infant Ear Disease And Carriage
Funder
National Health and Medical Research Council
Funding Amount
$1,131,530.00
Summary
Aboriginal children experience the highest rates of acute and chronic ear infections in the world, with resultant permanent ear damage, hearing loss and educational disadvantage. These infections are mainly bacterial, and Streptococcus pneumoniae (pneumococcus) is the predominant pathogen. Pneumococcal colonisation and infection begins within days of birth, many months before any potential immunological protection from infant pneumococcal conjugate vaccine may be expected. New strategies are nee ....Aboriginal children experience the highest rates of acute and chronic ear infections in the world, with resultant permanent ear damage, hearing loss and educational disadvantage. These infections are mainly bacterial, and Streptococcus pneumoniae (pneumococcus) is the predominant pathogen. Pneumococcal colonisation and infection begins within days of birth, many months before any potential immunological protection from infant pneumococcal conjugate vaccine may be expected. New strategies are needed to eliminate, or at least delay, this early-onset pneumococcal colonisation. One such strategy is the administration to the mother of pneumococcal vaccine, which may protect the newborn infant by leading to higher titres of transplacental or breast milk pneumococcal antibodies and-or by reducing carriage (and transmission to the infant) of maternal pneumococci. Previous small studies using this strategy have been encouraging, but there have been no studies properly evaluating carriage or disease endpoints in infants. The polysaccharide pneumococcal vaccine is currently recommended for all Aboriginal and Torres Islander persons aged 15 years or more in the Northern Territory but uptake of the vaccine has been poor. We propose to conduct a pilot study to determine if maternal immunisation with this vaccine, either in the third trimester of pregancy of immediately following delivery, can reduce pneumococcal carriage and the prevalence of middle ear disease among Aboriginal infants at seven months of age. We aim to recruit 210 Aboriginal women who have uncomplicated pregnancies from Darwin and remote communities in the Top End of the Northern Territory. Each subject and their infant offspring will be followed-up after vaccination and at birth, one , two and seven months after birth.Read moreRead less