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
Industrial Transformation Research Hubs - Grant ID: IH140100035
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Research Hub for Computational Particle Technology. ARC Research Hub for Computational Particle Technology. This research hub aims to develop and apply advanced theories and mathematical models to design and optimise particulate and multiphase processes that are widely used in the minerals and metallurgical industries. This should be achieved through detailed analysis of the fundamentals governing fluid flow, heat and mass transfer at different time and length scales, facilitated by various ....ARC Research Hub for Computational Particle Technology. ARC Research Hub for Computational Particle Technology. This research hub aims to develop and apply advanced theories and mathematical models to design and optimise particulate and multiphase processes that are widely used in the minerals and metallurgical industries. This should be achieved through detailed analysis of the fundamentals governing fluid flow, heat and mass transfer at different time and length scales, facilitated by various novel research techniques. Research outcomes including theories, computer models and simulation techniques, as well as well-trained young researchers, should have a significant impact across a range of industries of vital importance to Australia’s economic and technological future, including the minerals, metallurgical, materials, chemical, energy, pharmaceutical and environment sectors.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.
Industrial Transformation Research Hubs - Grant ID: IH130200031
Funder
Australian Research Council
Funding Amount
$3,273,780.00
Summary
ARC Research Hub for Advanced Technologies for Australian Iron Ore. ARC Research Hub for Advanced Technologies for Australian Iron Ore. This Research Hub aims to bring together three world-class groups covering fine particle beneficiation, raw materials handling, and iron ore characterisation to address the complex issues that arise from the different ore types that have emerged in recent years. This Research Hub will focus on the development and adoption of advanced beneficiation and handling t ....ARC Research Hub for Advanced Technologies for Australian Iron Ore. ARC Research Hub for Advanced Technologies for Australian Iron Ore. This Research Hub aims to bring together three world-class groups covering fine particle beneficiation, raw materials handling, and iron ore characterisation to address the complex issues that arise from the different ore types that have emerged in recent years. This Research Hub will focus on the development and adoption of advanced beneficiation and handling technologies into iron ore mining operations, and new knowledge for informing producers and end-users, while providing the training for a new generation of research leaders.Read moreRead less
Hot stage separation of non-ferrous fraction during iron ore reduction. The project aims to provide in-situ investigation of the behaviour and properties of the non-ferrous fraction in iron ore during reduction. The results aim to allow industry to: improve the quality of the final metallic iron product; economically separate and recover high-value non-ferrous impurities in the iron ore; reduce waste generated by ironmaking; and enable utilisation of, and add value to, iron ores that currently a ....Hot stage separation of non-ferrous fraction during iron ore reduction. The project aims to provide in-situ investigation of the behaviour and properties of the non-ferrous fraction in iron ore during reduction. The results aim to allow industry to: improve the quality of the final metallic iron product; economically separate and recover high-value non-ferrous impurities in the iron ore; reduce waste generated by ironmaking; and enable utilisation of, and add value to, iron ores that currently are not commercially viable due to their high impurity levels and low iron contents. The project aims to help expand the mining potential of the currently unviable iron ore deposits and enable industry to maintain the economic benefits from iron ore production in the years to come.Read moreRead less
A novel low-energy process route for primary copper production utilising synergistic hydro- and pyro-metallurgical processes. With increasing demand for copper metal, there is an urgent need to find new ways to efficiently treat lower grade ores. The new process offers a way of significantly reducing energy consumption and greenhouse gas emissions in primary copper production and making more efficient use of the world's copper resources.
Modelling of particle-fluid reactive flows coupled with phase changes. This project aims to develop an integrated mathematical model for reliably describing multiphase reactive flow coupled with phase change. Particle-fluid reactive flows with phase changes are widely encountered in many energy-intensive industries, yet process design and optimization are hindered by the lack of understanding of complex phenomena governing particularly multiphase flow, phase change and their interactions. The m ....Modelling of particle-fluid reactive flows coupled with phase changes. This project aims to develop an integrated mathematical model for reliably describing multiphase reactive flow coupled with phase change. Particle-fluid reactive flows with phase changes are widely encountered in many energy-intensive industries, yet process design and optimization are hindered by the lack of understanding of complex phenomena governing particularly multiphase flow, phase change and their interactions. The model will be achieved by means of combining advanced particle-scale numerical techniques with pre-database-based thermodynamic model, supported by physical experiments. The outcomes will be applied across a range of industries of vital importance to Australian economic and technological future. It will help transform Australian pyrometallurgy and chemical industries, open new markets for a range of Australian minerals like low-grade coal and iron/copper ore, and ultimately enhance competitiveness of Australian economy.Read moreRead less
Industrial Transformation Research Hubs - Grant ID: IH130100017
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Research Hub for Australian Steel Manufacturing. ARC Research Hub for Australian Steel Manufacturing. The aim of this Research Hub is to develop breakthrough process and product innovations to enable the Australian steel industry to improve its global competitiveness. Based on an integrated, value chain-wide approach to innovation in the steel sector the Research Hub includes projects on innovation strategy and management, customer-focused product development, innovation in coating and surfa ....ARC Research Hub for Australian Steel Manufacturing. ARC Research Hub for Australian Steel Manufacturing. The aim of this Research Hub is to develop breakthrough process and product innovations to enable the Australian steel industry to improve its global competitiveness. Based on an integrated, value chain-wide approach to innovation in the steel sector the Research Hub includes projects on innovation strategy and management, customer-focused product development, innovation in coating and surface engineering technology, and economic and environmental sustainability of iron and steelmaking.Read moreRead less
Three-dimensional flotation of fine particles. Three-dimensional flotation of fine particles. This project aims to research three-dimensional flotation of fine particles under both batch and continuous steady state conditions. In flotation, fine hydrophobic particles adhere to the two-dimensional surface of rising air bubbles, forming concentrate. In three-dimensional flotation, however, the particles adhere to and become embedded in a novel binder, forming a highly buoyant product. The process ....Three-dimensional flotation of fine particles. Three-dimensional flotation of fine particles. This project aims to research three-dimensional flotation of fine particles under both batch and continuous steady state conditions. In flotation, fine hydrophobic particles adhere to the two-dimensional surface of rising air bubbles, forming concentrate. In three-dimensional flotation, however, the particles adhere to and become embedded in a novel binder, forming a highly buoyant product. The process is very selective and arguably 1000 times faster than conventional flotation. The project is expected to provide the knowledge required to achieve scale-up, so the technology can be used to recover high value product from tailings waste, eliminating the capital impediment and possibly transforming the entire mining industry.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0230569
Funder
Australian Research Council
Funding Amount
$175,000.00
Summary
INTEGRATED PARTICLE IMAGE THERMOMETRY / VELOCIMETRY FACILITY. This proposal seeks to establish a specialised Particle Image Thermometry / Velocimetry (PITV) facility for simultaneous three-dimensional measurements of global temperature and velocity fields in complex flows. The proposed facility is needed to obtain experimental validations for theories and models developed for complex reacting and non-reacting flows that are strongly influenced by transient behaviour. Applications of PITV include ....INTEGRATED PARTICLE IMAGE THERMOMETRY / VELOCIMETRY FACILITY. This proposal seeks to establish a specialised Particle Image Thermometry / Velocimetry (PITV) facility for simultaneous three-dimensional measurements of global temperature and velocity fields in complex flows. The proposed facility is needed to obtain experimental validations for theories and models developed for complex reacting and non-reacting flows that are strongly influenced by transient behaviour. Applications of PITV include, but are not limited to, low-temperature reacting flows, mixing, jets, wakes, shear layers, time-dependent multiphase flows, unsteady turbulent flows, complex rotating machinery and other periodic flows, as well as natural convection studies.Read moreRead less