20% Human Albumin Solution FLuid Bolus AdministratIon TheRapy In Patients After Cardiac Surgery-II (HAS FLAIR-II)
Funder
National Health and Medical Research Council
Funding Amount
$125,396.00
Summary
Patients undergoing cardiac surgery often need a fluid bolus which is a volume of fluid given over a short period of time to improve their circulation. This intervention is essential as poor circulation may cause damage to important organs in the body such as the heart, lungs and kidneys. This study will allow doctors to make informed decisions about which type of fluid is better for their patients having cardiac surgery in the future.
New drugs for cancer therapy that overcome resistance to standard chemotherapeutics and stop the spread of cancer are essential to develop. My preliminary studies discovered a strategy to increase the activity and delivery of our novel compounds to enhance the killing of cancer cells. I will design innovative agents in an effort to provide more effective therapeutics with fewer side effects to reduce the pain of cancer patients undertaking chemotherapy who are in the battle of their lives.
A Pharmacological Targeting Approach Implementing Albumin As A Carrier Of A Novel Chemotherapeutic
Funder
National Health and Medical Research Council
Funding Amount
$560,659.00
Summary
New drugs for cancer therapy are essential to develop that overcome resistance to standard chemotherapeutics. We have developed potent anti-cancer chelators that bind to the abundant plasma protein, albumin. Our studies showed increased tumour cell uptake of the chelator, Dp44mT, mediated by albumin. We will elucidate the mechanisms of their albumin-mediated uptake, with the aim to implement albumin nanoparticles as carriers of novel chelators to selectively target tumours.
A Pharmacological Targeting Approach Implementing Albumin As A Carrier Of A Novel Chemotherapeutic
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
Novel agents that bind essential metals have emerged as a potential avenue for cancer therapy. My laboratory has developed potent anti-cancer agents, such as Dp44mT, that bind to the plasma protein, albumin. Notably, the uptake of Dp44mT into tumour cells was increased in the presence of albumin. My research will examine the mechanisms in the albumin-mediated increase in Dp44mT uptake into tumour cells, with the goal to develop albumin nanoparticles to selectively deliver our agents to tumours.
Randomised Comparison Of Fluid Resuscitation With Human Albumin Solution Or Normal Saline Among Critically Ill Patients
Funder
National Health and Medical Research Council
Funding Amount
$611,728.00
Summary
Human albumin solution is widely used for the emergency treatment of severely ill patients requiring fluid replacement, both in Australia and worldwide. However, a recent report suggests that compared to the other standard treatment (salt solution), the use of human albumin solution may be associated with a higher death rate (about six additional deaths among every one hundred patients treated). But, this report was based on data from a relatively small number of patients among whom there was a ....Human albumin solution is widely used for the emergency treatment of severely ill patients requiring fluid replacement, both in Australia and worldwide. However, a recent report suggests that compared to the other standard treatment (salt solution), the use of human albumin solution may be associated with a higher death rate (about six additional deaths among every one hundred patients treated). But, this report was based on data from a relatively small number of patients among whom there was a relatively small number of deaths, and there is widespread uncertainty among doctors about the reliability of the evidence and the implications for patient care. This is reflected in the large difference between intensive care units in the use of human albumin solution (in Australia, its use ranges from 10-90% of all patients needing fluid). Human albumin solution costs, about thirty times more than salt solution, and during 1998 more than 200,000 bottles of human albumin solution were administered to patients in Australia, at a cost of about A$35 million. In an effort to provide definitive evidence about the effects (and cost-effectiveness) of fluid replacement with human albumin solution, the Australia and New Zealand Intensive Care Society, in collaboration with the Australian Red Cross Blood Services and the Institute for International Health, has proposed the conduct of new large-scale study (SAFE - Saline vs Albumin Fluid Evaluation). This study will involve 7,000 patients from 15 intensive care units in Australia and New Zealand. These patients (all of whom require fluid replacement) will be randomly assigned to receive either human albumin solution or salt solution and outcome in terms of deaths and other serious events will be monitored over 28 days. Results will be available within 2 years of starting the study, and these are likely to influence the care of the majority of seriously ill patients admitted to intensive care units worldwide.Read moreRead less
The ClC-5 Cl- Channel, A Key Regulatory Role In Albumin Uptake By The Proximal Tubule
Funder
National Health and Medical Research Council
Funding Amount
$510,500.00
Summary
The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive pro ....The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive protein loss in the urine is primarily due to problems in the filtering units of the kidneys, rather than due to abnormalities in the reabsorption of protein in the kidney tubules. However, we consider that common abnormalities in the processes within the kidney tubules that regulate both the reabsorption of salt and the excretion of acid may result in concomitant high blood pressure and increased protein loss in the kidney. Thus the overall aim of the project is to investigate the mechanisms by which the complex responsible for protein uptake determines the interrelationship between protein reabsorption and catabolism and the ion transporting proteins in the membrane of the proximal tubule. This project will comprehensively characterise the mechanisms of protein uptake in kidney tubule cells. The exact nature of the interaction of the proteins involved in performing the salt reabsorption and ensuring correct catabolism of protein uptake with the actual protein uptake mechanism will be determined. As persistent proteinuria is the most important predictor of tubulointerstitial pathology and progressive decline in renal function in almost all renal disease, the understanding of the precise mechanism by which this occurs is essential in the design of renoprotective therapies.Read moreRead less
Next-generation Glioblastoma Multiforme Therapies Based On Multistage Delivery Nanovectors
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Nanomedicine provides novel therapies with enhanced treatment success and reduced side effects, which improve the patient’s quality of life. Drug delivery systems that are able to treat highly drug-resistant tumours such as glioblastoma multiforme (GBM) are a key target for nanomedicine-based therapies. We will investigate a new GBM treatment by developing a multistage delivery nanovector to selectively carry and release a combination of chemical and physical therapeutics.
Preclinical Development Of A Therapeutic Anticancer Antibody To C-Met
Funder
National Health and Medical Research Council
Funding Amount
$435,530.00
Summary
Many common cancers cannot be effectively treated. A range of these cancers (e.g. gastric and lung cancer) display the molecule c-Met on their cell surface. c-Met promotes tumour growth; therefore, blocking c-Met is a promising strategy for treating these cancers. However, no antibodies or drugs that target c-Met have been licensed. The therapeutics that are being developed to target c-Met all have considerable limitations. Thus, there is an opportunity to develop a 'best-in-class' therapeutic.