Evolution And Targeting Of Polysaccharide Biosynthesis In Leishmania Parasites
Funder
National Health and Medical Research Council
Funding Amount
$449,484.00
Summary
Leishmania are parasitic protozoa that cause devastating diseases in humans. This proposal will identify the enzymes involved in the biosynthesis of an unusual carbohydrate reserve material that accumulates in pathogenic stages of these parasites. Information on the structure and mode of action of these enzymes will be used to develop novel drugs that will be tested for anti-parasite activity.
Metabolomic Analysis Of Leishmania Parasites; Identifying Metabolic Pathways Required For Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Leishmania are single-celled parasites that target a major class of immune cell, affecting millions and killing thousands of people worldwide. We have developed new approaches for investigating how these parasites survive in the immune cells, and why different species of Leishmania cause markedly different pathologies. This information will be used to identify and validate new drug targets in these parasites.
Phase III Trial Of Radical Chemo-radiation Vs Radiation Alone In The Management Of Localised Bladder TCC.
Funder
National Health and Medical Research Council
Funding Amount
$194,875.00
Summary
This trial aims to see if the combination of Chemotherapy and Radiation treatment is indeed superior in eradicating the tumor and preserving the Bladder in a greater number of patients as compared to Radiation treatment alone. If the final results from this study do show chemoradiotherapy to be significantly superior to radiation alone, without an increase in morbidity ( especially long term side effects ) , this may lay the platform for a greater proportion of patients with localised bladder ca ....This trial aims to see if the combination of Chemotherapy and Radiation treatment is indeed superior in eradicating the tumor and preserving the Bladder in a greater number of patients as compared to Radiation treatment alone. If the final results from this study do show chemoradiotherapy to be significantly superior to radiation alone, without an increase in morbidity ( especially long term side effects ) , this may lay the platform for a greater proportion of patients with localised bladder cancer, being in the first instance considered for this organ( bladder) preserving approach something which has become a reality at a number of other sites of cancer with the use of multimodality treatment.Read moreRead less
OVERCOMING RESISTANCE OF HUMAN MELANOMA TO CHEMOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$499,500.00
Summary
Melanoma is the third most common cancer in women and men respectively. In NSW alone approximately 400 die each year from the disease. The main treatment of melanoma is surgical removal of the primary tumor on the skin but once the disease spreads beyond the skin to other organs there is no curative treatment. This study will identify whether resistance of melanoma to chemotherapy is due to failure to induce sufficient levles of pro-apoptotic BH3 only proteins and-or activation of apoptosis resi ....Melanoma is the third most common cancer in women and men respectively. In NSW alone approximately 400 die each year from the disease. The main treatment of melanoma is surgical removal of the primary tumor on the skin but once the disease spreads beyond the skin to other organs there is no curative treatment. This study will identify whether resistance of melanoma to chemotherapy is due to failure to induce sufficient levles of pro-apoptotic BH3 only proteins and-or activation of apoptosis resistance pathways. The results will be directly relevant to subsequent clinical trials in melanoma paients. Apoptosis may be triggered by chemotherapeutic agents but human melanoma shows wide variability in apoptotic responses to chemotherapy. Recent studies have shown that the Bcl-2 family of pro- and anti-apoptotic proteins and inhibitor of apoptosis proteins appear to be key regulators of the (mitochondrial) apoptosis pathway induced by chemotherapy. The activity of the proteins appear to be regulated by several signal pathways in the cell which may be activated by signals external or intrinsic to the cell. We wish to characterize the proteins involved in chemotherapy induced apoptosis, assess their variability between melanoma cells that are sensitive or resistant to apoptosis and characterize the signal pathways involved in regulating the proteins in human melanoma.Read moreRead less
Optimising Regulatory T Cell Depletion In Combination With Chemotherapy For Enhanced Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$264,816.00
Summary
The drug cyclophosphamide helps the immune system attack cancer by decreasing the number of immune cells that suppress an immune response to cancer ('Regulatory T cells'). This project combines standard chemotherapy with the drug cyclophosphamide in people with mesothelioma and lung cancer. The aim of the project is to find the dose of cyclophosphamide that maximally decreases Regulatory T cells in each patient, and determine the effect of this on anti-tumour immunity and response to treatment.
Coenzyme A Synthesis In The Human Malaria Parasite, Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falcip ....Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falciparum. The pathway mediates the conversion of the nutrient, vitamin B5, into a molecule called Coenzyme A. It plays an essential role in the intraerythrocytic parasite and our preliminary data indicate that components of this pathway hold significant potential as antimalarial drug targets. In this project we will use a range of biochemical and molecular biology approaches to characterise in detail the components of this pathway in the parasite and to explore the possibility that compounds that inhibit this pathway may be of value as much-needed new antimalarial agents.Read moreRead less
NEU-HORIZONS: The Neuroprotection And Therapeutic Use Of Riluzole For The Prevention Of Oxaliplatin Neurotoxicity Study.
Funder
National Health and Medical Research Council
Funding Amount
$382,402.00
Summary
Colorectal cancer is the second most commonly diagnosed cancer in Australia, with more than 13500 cases recorded annually. Oxaliplatin is an effective chemotherapy for the treatment of colorectal cancer. The major side-effect of oxaliplatin is the development of nerve damage that leads to loss of feeling in the hands and feet and significant disability. The aim of this study is to conduct a trial of a new treatment for oxaliplatin-induced nerve damage.