Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
ARC Centre of Excellence for Enabling Eco-Efficient Beneficiation of Minerals. The aim of the Centre is to progress scientific knowledge to establish transformational improvement in minerals beneficiation, essential for meeting global demand for metals. The research aims to achieve more selective, faster, and efficient separations, combining major advances in separation technologies with increased functionality of new reagents. The Centre outcomes will also ensure the sustainability of the miner ....ARC Centre of Excellence for Enabling Eco-Efficient Beneficiation of Minerals. The aim of the Centre is to progress scientific knowledge to establish transformational improvement in minerals beneficiation, essential for meeting global demand for metals. The research aims to achieve more selective, faster, and efficient separations, combining major advances in separation technologies with increased functionality of new reagents. The Centre outcomes will also ensure the sustainability of the minerals industry in Australia, through a significant reduction in cost, environmental impact, and through lower energy and water usage. The Centre also seeks to establish a new generation of scientists and research leaders in minerals beneficiation to support the innovation needed into the future by this major Australian industry.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100112
Funder
Australian Research Council
Funding Amount
$275,000.00
Summary
A Raman facility for advanced research supporting Australia’s natural gas, oil, coal and minerals industries. This modern Raman Spectroscopy facility will support the science and engineering that underpins the production and processing of Australia’s natural resources. Using high-pressure fibre optics, novel lasers and advanced imaging, the facility will enable the monitoring and improvement of processes and materials under extreme conditions.
Reducing health disparities for culturally and linguistically diverse peoples. This project aims to develop a greater understanding of migrants and the factors that predict poor health outcomes related to blood-borne viruses and sexually transmitted infections. The delayed access by migrants to healthcare from culturally and linguistically diverse backgrounds results in late diagnosis, low treatment uptake, and poorer health outcomes, with enhanced risk of infection and increased burden on the h ....Reducing health disparities for culturally and linguistically diverse peoples. This project aims to develop a greater understanding of migrants and the factors that predict poor health outcomes related to blood-borne viruses and sexually transmitted infections. The delayed access by migrants to healthcare from culturally and linguistically diverse backgrounds results in late diagnosis, low treatment uptake, and poorer health outcomes, with enhanced risk of infection and increased burden on the health system. The data collected in this project will assist in developing health services to meet these needs.Read moreRead less
Reconnecting Warlpiri communities with cultural heritage materials. The projects aims to reconnect Warlpiri communities with past documentation and recordings of their cultural heritage. Centred in Yuendumu, the project expects to unpack the significance of past documentation of cultural heritage for present day Warlpiri people who live in vastly different social worlds from their forebears. Through collaborations with Warlpiri families, and Partner Organisation, Pintupi Anmatyerr Warlpiri (PAW) ....Reconnecting Warlpiri communities with cultural heritage materials. The projects aims to reconnect Warlpiri communities with past documentation and recordings of their cultural heritage. Centred in Yuendumu, the project expects to unpack the significance of past documentation of cultural heritage for present day Warlpiri people who live in vastly different social worlds from their forebears. Through collaborations with Warlpiri families, and Partner Organisation, Pintupi Anmatyerr Warlpiri (PAW) Media and Communications, the project will see the set up of activities to engage with these materials and the production of resources for use by future generations.Read moreRead less
Conservation management of seed-eating birds in the tropical savannas. Biodiversity loss in the savannas indicates unsustainable management. This research will enhance our abilities to effectively manage Australia's tropical savannas, as well as contributing to several State and Territory, Commonwealth and international obligations to maintain biodiversity. Understanding the processes underlying current declines will also make the effects of future management or environment changes easier to pre ....Conservation management of seed-eating birds in the tropical savannas. Biodiversity loss in the savannas indicates unsustainable management. This research will enhance our abilities to effectively manage Australia's tropical savannas, as well as contributing to several State and Territory, Commonwealth and international obligations to maintain biodiversity. Understanding the processes underlying current declines will also make the effects of future management or environment changes easier to predict. Retaining threatened species can benefit remote and regional communities through tourism, and also through the extra employment required to implement the management prescriptions that will be developed from this research.Read moreRead less
A Future Beyond the Wall: Improving Post-release Employment Outcomes for People Leaving Prison. Engaging in meaningful work has been shown to reduce re-offending by ex-prisoners, but few prison releasees internationally or in Australia gain employment, and successful pathways to employment for this group are poorly researched and understood. This study aims to gather and analyse, for the first time, comparative data from Australian jurisdictions and employment agencies on the relationship betwee ....A Future Beyond the Wall: Improving Post-release Employment Outcomes for People Leaving Prison. Engaging in meaningful work has been shown to reduce re-offending by ex-prisoners, but few prison releasees internationally or in Australia gain employment, and successful pathways to employment for this group are poorly researched and understood. This study aims to gather and analyse, for the first time, comparative data from Australian jurisdictions and employment agencies on the relationship between in-prison and post-prison vocational education and employment programs, employment and recidivism. It aims to identify effective elements, strategies, program and policy directions in offender training and employment. This is a unique partnership amongst key academics in the field, peak national bodies, correctional and employment organisations.Read moreRead less
ARC Centre of Excellence for Indigenous Futures. ARC Centre of Excellence for Indigenous Futures. The ARC Centre of Excellence for Indigenous Futures aims to transform and improve the life chances of Indigenous Australians by utilising Indigenous knowledges in unique trans-disciplinary cross-sector designed research to enhance our understanding about the complex nature of Indigenous intergenerational inequity. The Centre expects to generate new knowledge to enable evidence-based policy formulati ....ARC Centre of Excellence for Indigenous Futures. ARC Centre of Excellence for Indigenous Futures. The ARC Centre of Excellence for Indigenous Futures aims to transform and improve the life chances of Indigenous Australians by utilising Indigenous knowledges in unique trans-disciplinary cross-sector designed research to enhance our understanding about the complex nature of Indigenous intergenerational inequity. The Centre expects to generate new knowledge to enable evidence-based policy formulation and implementation including best practice models. The Centre will be entirely led by Indigenous researchers working with communities, government agencies and practitioners to strengthen the delivery of outcomes and linkages intentionally focused on all four of the National Agreement Close The Gap -2020’s Priority Reform areas.Read moreRead less
Mammal declines in northern Australia: science for conservation and recovery. Australia’s unique mammal fauna is a rich biological heritage for the nation. It provides a wealth of ecosystem services, and many mammal species have special cultural or aesthetic value. However, our mammals are sadly depleted, and we already have the worst record of recent mammal extinction of any nation. Preventing further mammal extinctions, and managing environments to allow declined mammals to recover, will be of ....Mammal declines in northern Australia: science for conservation and recovery. Australia’s unique mammal fauna is a rich biological heritage for the nation. It provides a wealth of ecosystem services, and many mammal species have special cultural or aesthetic value. However, our mammals are sadly depleted, and we already have the worst record of recent mammal extinction of any nation. Preventing further mammal extinctions, and managing environments to allow declined mammals to recover, will be of great benefit to Australian biodiversity and to the ecosystem processes and human values that depend on it.Read moreRead less