New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways res ....New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways responsible for how a cell manages stress by regulating levels of proteins involved in the cellular stress response. Discoveries made during the course of this research will provide knowledge of gene and protein interactions that will be important in the future to develop anti-cancer therapies. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less
Optimal Duration Of Neoadjuvant Androgen Deprivation Therapy In Localised Prostate Cancer Treated By Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$422,335.00
Summary
The 96.01 trial aims to find out whether androgen deprivation (AD) administered prior to and during radiotherapy (i.e., neo-adjuvant AD) will improve outcomes in patients with locally advanced prostate cancer that is considered inoperable and is treated for cure by radiotherapy. The trial also aims to find out whether six months AD produces outcomes superior to those achieved by three months AD. The trial has been running since 1996 and involves 802 men who attend 19 cancer treatment centres acr ....The 96.01 trial aims to find out whether androgen deprivation (AD) administered prior to and during radiotherapy (i.e., neo-adjuvant AD) will improve outcomes in patients with locally advanced prostate cancer that is considered inoperable and is treated for cure by radiotherapy. The trial also aims to find out whether six months AD produces outcomes superior to those achieved by three months AD. The trial has been running since 1996 and involves 802 men who attend 19 cancer treatment centres across Australia and New Zealand. It would not have been possible without the continuous funding support of the NHMRC. So far this trial has shown that AD does prevent prostate cancer from returning after radiotherapy. This is very important because the need for treatment of recurrent cancer (usually AD for the rest of the patient's life) is halved by 6 months AD compared to standard treatment (radiotherapy alone). However, it is now necessary to observe the patients in this trial for another 5 years to find out whether AD also prolongs life, and whether 6 months AD is more effective than 3 months. Further patient follow up is also necessary to identify whether some men respond better to treatment than others. This is very important because it will enable treatment to be tailored to individual patients, in particular those who require more treatment than is given in this trial. This funding application is therefore to enable patient follow up on this large scale trial for another 5 years.Read moreRead less
Optimal Duration Of Neoadjuvant Androgen Deprivation Therapy In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$275,000.00
Summary
Each year approximately 8000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation' [AD] therapy) can produce shrinkage of prostate cancer. In fact AD has caused temporary but valued relief to millions of men with cancer ....Each year approximately 8000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation' [AD] therapy) can produce shrinkage of prostate cancer. In fact AD has caused temporary but valued relief to millions of men with cancer of the prostate that has spread throughout the body for the last five decades, worldwide. It remains uncertain however whether AD administered before surgery or radiation will benefit any of the 8000 men each year who develop localised cancer by shrinking the cancer first. In 1996 a trial involving 800 men across Australia and New Zealand commenced under the auspices of the Trans-Tasman Radiation Oncology Group (TROG) to answer the questions: 1 - Does either 3 or 6 months AD prior to radiotherapy reduce the chances of recurrence of the cancer after radiotherapy? 2 - Does such therapy reduce the volume of tissue requiring radiotherapy and hence the chances of long term side effects after radiotherapy? This grant will support collection of follow-up information from the trial and hence answers to the questions asked.Read moreRead less
Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.
Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when t ....Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when they are most likely to work. In this project, we are developing new radiolabelled compounds that will enable the imaging of tumours, tumour metastases and CNS diseases states.Read moreRead less
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
Encapsulation of magnetic nanoparticles for the hyperthermia treatment of liver cancer. This project will provide targeted hyperthermia treatment for liver cancer. The treatment will be non systemic and therefore, unlike radiotherapy and chemotherapy, will cause minimal collateral damage to healthy tissue within the patient. Liver cancer is one of the commoner forms of cancer in humans with estimates of up to 2 million patients per year being affected worldwide. Currently 95% of these patients w ....Encapsulation of magnetic nanoparticles for the hyperthermia treatment of liver cancer. This project will provide targeted hyperthermia treatment for liver cancer. The treatment will be non systemic and therefore, unlike radiotherapy and chemotherapy, will cause minimal collateral damage to healthy tissue within the patient. Liver cancer is one of the commoner forms of cancer in humans with estimates of up to 2 million patients per year being affected worldwide. Currently 95% of these patients will die from the condition. This project will lead to improvements in health outcomes for liver cancer patients. As a consequence of the worldwide demand for this treatment, and related equipment, the project will generate foreign exchange earnings through exports and new job opportunities in the clever end of small business enterprise.Read moreRead less
Structural and pharmaceutical studies on a novel human protein, MIC-1. Cancer and obesity are two of the main health problems facing Australia, as reflected by the National Research Priority: Promoting and Maintaining Good Health. This project will develop new diagnostic tools for early cancer detection and prognosis using the protein, MIC-1. MIC-1 is responsible for cachexia, a wasting disorder responsible for 25% of cancer deaths, which has no effective therapy. MIC-1 and antibodies neutrali ....Structural and pharmaceutical studies on a novel human protein, MIC-1. Cancer and obesity are two of the main health problems facing Australia, as reflected by the National Research Priority: Promoting and Maintaining Good Health. This project will develop new diagnostic tools for early cancer detection and prognosis using the protein, MIC-1. MIC-1 is responsible for cachexia, a wasting disorder responsible for 25% of cancer deaths, which has no effective therapy. MIC-1 and antibodies neutralising MIC-1 may provide therapeutic agents to control cancer cachexia and severe obesity. The project will optimise these molecules for therapeutic uses. These diagnostic and therapeutic tools will form the basis of a spin-off company for commercialisation. Read moreRead less
Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in ....Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in order to develop more potent drug analogues. Development of these molecules will involve a collaborative and multidisciplinary link with our industry partner and the use of frontier technologies that may lead to improved health and economic outcomes for Australia. Read moreRead less