The Analgesic Evaluation Of Novel Natural Products From The Australian Plant Barringtonia Acutangula
Funder
National Health and Medical Research Council
Funding Amount
$174,500.00
Summary
This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that wi ....This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that will allow for their pharmacological evaluation as potential analgesic drugs.Read moreRead less
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
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Immuno-polymeric Drugs For Prostate Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$626,995.00
Summary
Prostate cancer is the most common cancer in men over 50 and the second most frequent cause of cancer deaths in Western society. Docetaxel is the first line of chemotherapy when other intervention strategies are unsuccessful, but 30% of patients suffer from severe side-effects. To address this problem, we will utilise carriers for docetaxel that directly target prostate tumours using a novel antibody approach. This increases accumulation at the tumour site while decreasing off-target toxicity.
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.
Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control ....Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control skin diseases in the dog. Skin diseases are a significant problem in veterinary science and this project will not only provide an effective therapeutic option, but also reduce animal (and client) distress when suffering skin disease and/or adverse effects from traditional therapy.Read moreRead less
KLK4 Is A Master Regulator Of Tumour Microenvironment Remodelling In Prostate Cancer And Bone Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$596,305.00
Summary
The current biomarker for prostate cancer, PSA, belongs to a large family of related proteins called KLK enzymes. We have evidence that one of these enzymes, KLK4, regulates many different pathways involved in tumour spreading especially to bones. This project will determine the specific components involved with a view to finding better biomarkers of tumour spread and bone metastasis and designing better treatments for these aspects of the disease.
Nitrogen Removal in Wastewater Treatment Using the Nitrite Pathway. Nitrogen removal from our wastewater is becoming very important in most parts of Australia to protect our unique aquatic environment. This removal is achieved biologically through two steps: Nitrification converts ammonium via nitrite to nitrate; and denitrification converts nitrate via nitrite again to harmless nitrogen gas. This project aims to develop a method that allows this process to go just via nitrite, instead of nitrat ....Nitrogen Removal in Wastewater Treatment Using the Nitrite Pathway. Nitrogen removal from our wastewater is becoming very important in most parts of Australia to protect our unique aquatic environment. This removal is achieved biologically through two steps: Nitrification converts ammonium via nitrite to nitrate; and denitrification converts nitrate via nitrite again to harmless nitrogen gas. This project aims to develop a method that allows this process to go just via nitrite, instead of nitrate, to nitrogen gas. This would significantly reduce oxygen and/or carbon requirement in nitrogen removal. If successful, the new operating method will allow modern wastewater treatment plants to achieve a better effluent quality at lower costs.Read moreRead less
Novel pharmacological agents to target stroke-induced brain injury. There is a looming stroke epidemic in Australia. 72% of Australian stroke sufferers are over the age of 65 and whereas in 1997 only 12% of Australians were in that age group, by 2030 that number will have increased to 23%. There is an urgent need for novel therapies. This project will aid the development of a novel anti-stroke therapy.