The Microenvironmental Drivers Of T Cell Regulation In Metastatic Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,302,611.00
Summary
COX2 inhibitors are drugs commonly used by cancer patients to relieve pain and inflammation. Using human breast cancer samples and mouse models of breast cancer, we show that pathways targeted by these drugs provide an immunological brake that prevents T cells being activated as strongly as they could be, and which has not been studied. This project is expected to yield important anti-cancer targets that could be used to develop a new class of cancer drugs.
Arachidonic Acid Modulation Of Glutamate Transporters
Funder
National Health and Medical Research Council
Funding Amount
$286,980.00
Summary
Neurotransmitter transporters play a key role in regulating the dynamics of neurotransmission and are also the targets for a number of very important drugs. Glutamate is the predominant neurotransmitter responsible for fast excitatory neurotransmission and glutamate transporters are responsible for controlling glutamate concentrations to maintain normal neurotransmission. The failure of glutamate transporters has been implicated as playing a key role in brain damage following a stoke and also fo ....Neurotransmitter transporters play a key role in regulating the dynamics of neurotransmission and are also the targets for a number of very important drugs. Glutamate is the predominant neurotransmitter responsible for fast excitatory neurotransmission and glutamate transporters are responsible for controlling glutamate concentrations to maintain normal neurotransmission. The failure of glutamate transporters has been implicated as playing a key role in brain damage following a stoke and also for long term neurological disorders such as Alzheimer's disease. In this project we shall investigate a novel mechanism for regulating the activity of glutamate transporters and explore the possibility of pharmacologically manipulating glutamate transporters. This work may lead to the development of novel compounds that improve transporter function and reduce the pathological consequences of impaired transporter function. Such compounds may have therapeutic potential as neuroprotectants in the treatment of neurological disorders such ischaemic brain damage or neurodegenerative disorders such Alzheimer's disease.Read moreRead less
COX-2 Inhibitors And The Development Of Unstable Angina And Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$171,450.00
Summary
Anti-inflammatory drugs (sometimes called NSAIDs) are widely used in the treatment of arthritis and also as general purpose pain killers. Up to 10 million prescriptions are written each year for these drugs in Australia. Some of the older versions of these drugs like ibuprofen (eg Brufen) and naproxen (trade name Naproxen) cause side effects which can be serious. Damage to the stomach is a particular problem and this can lead to serious bleeding or perforation of ulcers. Less well recognized are ....Anti-inflammatory drugs (sometimes called NSAIDs) are widely used in the treatment of arthritis and also as general purpose pain killers. Up to 10 million prescriptions are written each year for these drugs in Australia. Some of the older versions of these drugs like ibuprofen (eg Brufen) and naproxen (trade name Naproxen) cause side effects which can be serious. Damage to the stomach is a particular problem and this can lead to serious bleeding or perforation of ulcers. Less well recognized are the adverse effects of these drugs on the heart and the kidneys. The older fashioned members of this class of drug are rapidly being replaced by newer agents known as COX-2 inhibitors. Popular examples in Australia are celecoxib (trade name Celebrex) and rofecoxib (trade name Vioxx). These drugs are heavily promoted as being safer than the older NSAIDs. In the case of the stomach, this claim seems to be correct. However, the effects of the new COX-2 inhibitors on the circulation have not been fully assessed. Recently, claims have been made that these drugs may increase the risk of heart attacks. If this were true, it would be an effect that was unique to COX-2 inhibitors as it has not been reported with the older NSAIDs. We plan to carry out a 3 year study in Newcastle hospitals in which we compare the use of COX-2 inhibitors in a group of patients admitted to hospital with a heart attack or unstable angina with that of a control group of patients who were admitted to hospital around the same time, but not for heart problems. We are interested in whether COX-2 inhibitors are associated with an increased risk of heart attacks and whether use of small doses of aspirin protects against this effect. Depending on the results we may be able to improve the safety of these drugs in patients at risk of heart attacks.Read moreRead less
COX-2 INHIBITORS AS A CAUSE OF HEART AND RENAL FAILURE
Funder
National Health and Medical Research Council
Funding Amount
$271,610.00
Summary
Non-steroid anti-inflammatory drugs (NSAIDs) have pain-killing and anti-inflammatory properties. For many years Australia had a higher use of these drugs than other countries. The drugs are quite toxic, and in susceptible individuals may cause ulceration and bleeding from the stomach and duodenum, kidney damage and fluid congestion leading to heart failure. Each of these conditions carries a high morbidity, particularly in the elderly. Because of concerns about toxicity, the use of NSAIDs in Aus ....Non-steroid anti-inflammatory drugs (NSAIDs) have pain-killing and anti-inflammatory properties. For many years Australia had a higher use of these drugs than other countries. The drugs are quite toxic, and in susceptible individuals may cause ulceration and bleeding from the stomach and duodenum, kidney damage and fluid congestion leading to heart failure. Each of these conditions carries a high morbidity, particularly in the elderly. Because of concerns about toxicity, the use of NSAIDs in Australia fell during the 1990s by around 40%. Newer allegedly safer forms of NSAIDs called COX-2 inhibitors have been introduced into the Australian market. The first 2 drugs to be marketed are called Celebrex and Vioxx. These drugs appear to be safer for the stomach and duodenum, but the true effects on the kidney and heart are as yet unclear. COX-2 inhibitors have been very widely used with over 1.7 million prescriptions issued since their listing on the Pharmaceutical Benefits Scheme in August 2000. Most of this use appears to be in addition to prescribing of the older NSAIDs rather than as a replacement for them. The purpose of this study is to compare the safety of the new COX-2 inhibitors with that of the older NSAIDs. We are interested in how often they cause renal failure and heart failure. The investigators will use well-established research methods to estimate the risk of heart failure and kidney failure with these drugs in the Australian community. Data from the study will form the basis of clinical practice guidelines for the safe use of these drugs in Australia.Read moreRead less
Design And Use Of Human Hematopoietic Prostaglandin D2 Synthase Inhibitors In Allergic Asthma And Bone Diseases
Funder
National Health and Medical Research Council
Funding Amount
$517,960.00
Summary
Many currently used non-steroidal anti-inflammatory drugs are burdened by side effects such as gastrointestinal bleeding or increased risk of heart attack. This is because they ablate the production of a class of molecules called prostaglandins. We believe it is possible to fine tune the action of these drugs and reduce the side effect risk. There is evidence to suggest that only some prostaglandins are involved in inflammation, so the risk of side effect can be reduced by blocking the productio ....Many currently used non-steroidal anti-inflammatory drugs are burdened by side effects such as gastrointestinal bleeding or increased risk of heart attack. This is because they ablate the production of a class of molecules called prostaglandins. We believe it is possible to fine tune the action of these drugs and reduce the side effect risk. There is evidence to suggest that only some prostaglandins are involved in inflammation, so the risk of side effect can be reduced by blocking the production of only a small set. One prostaglandin, prostaglandin D2, is known to cause many characteristics of allergic asthma and may also contribute to osteoarthritis, although the evidence for this is contradictory. We will determine any therapeutic benefit to blocking the production of prostaglandin D2 in these diseases by developing compounds that only inhibit the enzyme responsible for its production.Read moreRead less
The Effect Of Glucosamine Sulphate On Structural Disease Progression In Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$1,250,214.00
Summary
Osteoarthritis (OA) is a joint disease characterized by a progressive loss of cartilage and joint space resulting in increasing pain and difficulty performing usual daily activities. OA is the leading health problem amongst older Australians and a National Health Priority area. There is no known cure for OA and no intervention demonstrated to slow disease progression or delay time to joint replacement surgery. Currently patients are managed symptomatically with all clinical guidelines recommendi ....Osteoarthritis (OA) is a joint disease characterized by a progressive loss of cartilage and joint space resulting in increasing pain and difficulty performing usual daily activities. OA is the leading health problem amongst older Australians and a National Health Priority area. There is no known cure for OA and no intervention demonstrated to slow disease progression or delay time to joint replacement surgery. Currently patients are managed symptomatically with all clinical guidelines recommending paracetamol as 'the preferred long term oral analgesic'. This recommendation is based on the increased risk of serious gastrointestinal, cardiovascular and renal diseases with long-term NSAIDs use in older people. However, NSAIDs appear to provide better pain relief for patients with more than mild joint pain. Amongst patients with OA, there is much demand for the dietary supplement glucosamine sulphate. Product marketing has led to the belief that glucosamine is able to slow the rate of joint destruction and cartilage loss and help ease joint pain with, in contrast to NSAIDs, little risk of side effects. However, the few trials conducted to date have been inconclusive. If the marketing claims are unjustified, many older people are wasting limited financial resources and due to unrealistic expectations of the benefit of glucosamine, placing a lower priority on lifestyle changes of proven effectiveness, such as regular exercise and weight loss. A total of 900 patients with knee OA will be randomly allocated to glucosamine sulphate or matching placebo capsules for two years. The main outcomes will be the rate of joint space narrowing, use of NSAIDs and physical disability. If glucosamine results in slowing disease progression or in reducing NSAIDs consumption, the widespread use of this product would effectively decrease pain, disability and NSAIDs-related illnesses amongst the increasing number of people with OA.Read moreRead less