Pharmacokinetics And Pharmacodynamics Of High Dose Melphalan In Myeloma Patients Undergoing An Autograft
Funder
National Health and Medical Research Council
Funding Amount
$465,761.00
Summary
Myeloma is a cancer of the bone marrow that affacts over 1000 people every year in Australia. The treatment is difficult and toxic, particularly as patients who develop the disease are often older (typically 50-70 years) and have kidney problems as part of the disease. Most patients will have better control of their disease if they receive a high dose of a potent drug called melphalan. Melphalan is toxic to the bone marrow, so melphalan is followed by an infusion of the patients' bone marrow or ....Myeloma is a cancer of the bone marrow that affacts over 1000 people every year in Australia. The treatment is difficult and toxic, particularly as patients who develop the disease are often older (typically 50-70 years) and have kidney problems as part of the disease. Most patients will have better control of their disease if they receive a high dose of a potent drug called melphalan. Melphalan is toxic to the bone marrow, so melphalan is followed by an infusion of the patients' bone marrow or blood stem cells (a bone marrow transplant). Dosing of melphalan is according to a standard schedule that does not account for individual factors. We know that the drug disappears from the blood quite quickly, and how quickly it disappears probably affects its toxicity and effectiveness. Higher doses are more toxic and patients can die as a result of their transplant, lower doses do not control the disease as well. Not many places in the world measure the levels of melphalan in the blood. At The Childrens Hospital we have already performed the largest study of melphalan bloods in children. With the formation of the NSW Bone Marrow Transplant Network, we have joined with doctors who treat adults with myeloma and realised that we were in a position to answer some major questions about the effectiveness of melphalan in myeloma and how important it was to get lower or higher levels of the drug in the patient's blood. We are planning what will be the largest study of melphalan blood levels in the world (more than 100 myeloma patients). By measuring the melphalan in their blood and then following what happens to the patients, we will be able to work out whether the dose of melphalan we are using is ideal; if there are things about the patient that tell us we should give a bigger or smaller dose and if the blood levels are related to how much toxicity the patient has after transplant and how well the myeloma is controlled. This should improve the outcome of myeloma patients.Read moreRead less
Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients r ....Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients reaching the gut cause the release of hormones from cells in the lining of the stomach and intestine. These hormones tell the brain when enough food has been consumed. It used to be thought that the hormones travelled in the blood stream to affect the brain directly. Recently, it has become clear that much of their effect is actually carried by sensory neurons with endings in the lining of the gut. The hormones have a powerful effect the sensory nerve fibres which then send electrical signals in nerve fibres running in the vagus nerve to the brain. Here they make connections which eventually influence the centres that control feeding. There is much to understand about how hormones affect the sensory nerve endings in the wall of the gut, whether all nerve fibres are affected the same way and what sort of information is conveyed to the brain. This project will use electrophysiological methods to identify which nerve fibres are activated by hormones, whether different hormones affect different nerve fibres, which nutrients activate particular nerve fibres and whether nerve fibres make selective contacts with particular hormone-releasing cells. These questions are important for understanding how we normally stop feeding and how drugs might be designed to cause feelings of fullness earlier in each meal.Read moreRead less
The Role Of A Low Emulsifier Diet To Treat Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$447,603.00
Summary
Currently, there are no specific diets known to treat Crohn’s disease (CD). Initial lab- and animal-based studies have indicated emulsifiers added to food drive inflammation in CD, but no human trials completed. This study will design and feed high and low emulsifier diets to healthy and CD subjects and measure markers of inflammation. This will establish the role of a low emulsifier diet to treat CD.
Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Bacterial pathogens are a major cause of illness and death, producing diseases ranging from acute infections to cancer. However, not all infected individuals will succumb to these pathologies. What factors dictate which individuals develop these diseases is an important complex question. The core focus of my research is the identification and characterisation of novel host factors that are involved in resistance or susceptibility to bacterial-associated diseases of the gastrointestinal tract.