Novel Genes And Protein In Non-alcoholic Fatty Liver Disease: Potential Basis Of A Serum-based Assessment Of Disease Sta
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infe ....The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infection with the hepatitis C virus. We obtained liver biopsies from patients with NAFLD, 80% of whom had NASH, and determined the expression profile analysis of each subject using 19,200 element microarrays. Our data demonstrates the concordant differential expression of 130 genes, in subjects with NAFLD that were categorizes into 6 major metabolic and regulatory pathways. Many of these genes represented uncharacterised genes. Utilising an extensive bioinformatics approach we have been able to define the genes and their protein product. The use of these proteins as a diagnostic tool for the detection of NAFLD forms the basis of a provisional patent application. However, measurements of protein levels in tissue and sera from patients with NAFLD are needed for the development of a diagnostic method. Such information would also provide significant insight into the pathogenesis of NAFLD. The AIMS are: 1) Production of antibodies against proteins encoded by candidate genes Expression profile of candidate genes 3) Expression of proteins encoded by candidate genes in patients with NAFLDRead moreRead less
Non-invasive Measurement And Imaging Of Hepatic Iron Concentrations Using Nuclear Magnetic Resonance
Funder
National Health and Medical Research Council
Funding Amount
$341,210.00
Summary
Iron overload diseases such as genetic haemochromatosis and thalassaemia affect up to 0.5% of the world's population. These diseases result in deposition of dangerously high concentrations of iron in tissues of the body. Organs such as the liver and heart are at particular risk of being damaged. In order to manage a patient's condition optimally, a knowledge of their tissue iron concentrations is required. Currently the most direct and reliable way of achieving this is to remove a small sample o ....Iron overload diseases such as genetic haemochromatosis and thalassaemia affect up to 0.5% of the world's population. These diseases result in deposition of dangerously high concentrations of iron in tissues of the body. Organs such as the liver and heart are at particular risk of being damaged. In order to manage a patient's condition optimally, a knowledge of their tissue iron concentrations is required. Currently the most direct and reliable way of achieving this is to remove a small sample of the patient's liver for chemical analysis. Apart from the fact that the procedure is unpleasant and carries some risk, the measurement made by this method has some uncertainty because the liver iron concentration can vary significantly from place to place within the liver. The aim of this project is to test the validity of a new non-invasive method of measuring and imaging the liver iron concentrations of a patient. In addition, the potential to use the new technology for detecting and imaging liver cirrhosis in iron overloaded patients will be evaluated. If successful, the project may lead to a more accurate method of measuring tissue iron concentrations and eliminate the need for invasive procedures.Read moreRead less
Development Of Anti-CXCR2 Monoclonal Antibodies For Tumour Therapy
Funder
National Health and Medical Research Council
Funding Amount
$174,867.00
Summary
New therapies to treat cancers and inflammatory diseases are urgently required. Our aim is to develop a new treatment for cancer and inflammation, by blocking the chemokine receptor CXCR2 which is central to angiogenesis (blood vessel growth) and inflammation. We have produced a highly effective monoclonal antibody (mAb) inhibitor of CXCR2, that is suitable for preclinical and clinical development. The project aims to examine the efficacy of this mAb in mouse tumour models and inflammation.
The Development Of Store Operated Calcium Channel Monoclonal Antibody Inhibitors As A Therapeutic Option For Breast Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$230,753.00
Summary
Despite recent advances in the treatment of breast cancer, a significant proportion of women with this disease receive little benefit from currently available treatments and die from breast cancer. Hence, new therapies for the breast cancers with the poorest prognosis are needed. This grant exploits our earlier finding that a specific calcium channel is a likely therapeutic target for breast cancer. Funding from this grant will be used to develop an inhibitory monoclonal antibody to this target.
The majority of deaths from cancer are due to metastasis, which is the formation of secondary tumours at sites remote from the primary tumour. Metastasis involves conversion of some tumour cells to an invasive, migratory form in a process that is controlled by small genetic regulators known as microRNAs. In this project we will conduct experiments aimed to provide a proof of principle demonstration in mice that microRNAs can be used to block the formation of metastases.
Development Of Modified IGF-binding Proteins As Novel Anti-cancer Chemotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$77,375.00
Summary
We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof ....We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof of concept in vivo in order to attract commercial funding for clinical trials.Read moreRead less
Improved Formulations Of Anti-cancer Agents 5-Fluorouracil And Oxaliplatin Using Excipient Technology
Funder
National Health and Medical Research Council
Funding Amount
$202,973.00
Summary
Chemotherapy plays a key role in cancer treatment, however, problems persist with severe adverse toxic effects. Combinations of anti-cancer agents give better results, but these agents still have major negative effects, for example, on veins and peripheral nerves and they must be given separately. We have developed a novel, all-in-one formulation of Oxaliplatin with 5-Fluorouracil and Leucovorin, with the potential for fewer toxic effects and improved patient care.
Targeted Alpha Therapy For Metastatic Breast Cancer Using Alpha-Herceptin
Funder
National Health and Medical Research Council
Funding Amount
$332,420.00
Summary
The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of H ....The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of HIV-1 to provide universal coverage of the major HIV-1 strains for a global population. The synthetic systematically designed HIV-1 vaccine will be delivered using our newly developed prime-boost immunisation regime that induces particularly high levels of cell-mediated immunity.Read moreRead less
Development Of Anti-metastatic And Tumour Targeting Reagents By Design Of Inhibitors To Specific Eph/ephrin Cell-cell
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (E ....Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (Ephs) and their membrane-bound ephrin ligands are crucial mediators of cell adhesion and motility and are notably overexpressed in metastatic tumours rather than primary (benign) lesions5. Our laboratories were the first to identify EphA3 7, and one of the first to isolate its ligand, ephrin-A5. EphA3 was isolated from acute lymphoblastoid leukemia and malignant melanoma patients, where increasing expression levels correlate with metastatic progression. Soluble, non-clustered forms of Ephs and ephrins are effective inhibitors of Eph activity 3 and provide opportunities to generate specific drugs for cancer therapy. We now propose a research and development program for the development of EphA3-specific drugs and their production for pre-clinical and clinical evaluation for placement onto a national and international market.Read moreRead less