2001 RESEARCH - 8 projects, $80,000 (- $10,000 for training) Gene expression in prostate and breast cancer Chief Investigator: Dr B B Yeap Amount Awarded: $10,000.00 Prostate and breast cancer are important causes of ill health and death in Australians. Conventional treatment cures many but some cancers progress after a period of time despite continuing treatment. Thus, newer and more effective treatments are needed. The thiazolidinedione class of drugs used to treat patients with diabetes activate a receptor called the peroxisome proliferator-activated receptor gamma (PPARg) which controls the development of fat cells. Recently it has been proposed that PPARg may play a key role in controlling the growth of prostate and breast cancer cells, and thus activation of it might be of use in treating patients with these cancers. In this project samples from patients with breast cancer were examined to assess the quantity of PPARg protein present. Breast cancer tissue contained less than normal breast tissue. Human prostate and breast cancer cells were then grown in the laboratory to study the effect of activating PPARg, which resulted in slowing of cancer cell growth. This research supports the role of PPARg as a key factor influencing the growth of prostate and breast cancers. Activation of PPARg by the use of the thiazolidinedione class of drugs slows prostate and breast cancer cell growth, and affects the quantity of PPARg messenger RNA present in these cells. A better understanding of the biology of PPARg in these cancers and would assist the development of new anticancer therapy. Early detection of septicaemia in children and young adults Chief Investigators: Dr I Dey, Dr P Sprivulis Amount Awarded: $8,130.00 The cause and severity of high temperatures in children and young adults is often very difficult to ascertain, causing concern to both doctors and parents. The researchers were funded to study a product that becomes present in the blood during infections. By measuring the levels of this substance, the team believes that they will be able to determine the severity of the infection and more quickly identify those children that may need high level treatment. This could allow earlier diagnosis of conditions such as meningococcal septicaemia, and save lives. The researchers tested whether two different blood tests could be used alone or in combination to detect life threatening meningococcal infections early in the course of the illness, to allow earlier commencement of treatment and increase the chance of surviving. Blood taken from young adults and children who had presented with fever was checked for D-Dimer and Pro-Calcitonin levels. Preliminary results indicate that both blood tests assist the early detection of meningococcal septicaemia, however firm conclusions will be drawn only after the completion of the trial in about 12 months time. This work could have a profound effect in saving the lives of many children and young adults. Iron absorption in patients with anaemia Chief Investigators: A/Prof J K Olynyk, Dr D Trinder, Dr G Vautier Amount Awarded: $10,000.00 Low blood counts due to a lack of iron occurs in 2% of our population. Possible causes of iron deficiency include reduced dietary intake, reduced absorption from the gastrointestinal tract, or increased loss of iron usually in the form of gastrointestinal bleeding. Despite thorough investigation, one third of these people do not have an apparent cause for the lack of iron. Iron is an important element in human physiology. It is present in all cells associated with blood molecules and is essential for the utilisation of oxygen. Iron deficiency can cause a wide range of clinical consequences from non-specific fatigue to cardiac failure. A protein called DMT1 is important for extracting iron from the food within the gut and passing it into the intestinal cell, and the researchers wished to see if there is a problem with the protein that is causing the lack of iron in those with iron deficiency of unknown cause. The researchers studied DMT1 levels in normal individuals, subjects with iron deficiency of known cause and subjects with iron deficiency of unknown cause. Normal subjects had low levels of DMT1 and subjects with iron deficiency of known cause and of unknown cause had elevated levels of DMT1 - however there were no differences between the last two groups. This study has shown that DMT1 levels are appropriately elevated in subjects with iron deficiency irrespective of the cause. Thus, the hypothesis that failure of expression of DMT1 could account for low iron levels in patients with unexplained cause of iron deficiency has now been ruled out, which will lead researchers to investigate other causes. Early Detection of Lung Cancer Chief Investigators: Dr A J Hodge, Ms M Sturm Amount Awarded: $9,500.92 In spite of the removal of diseased tissue in the early stage lung cancer, a significant number of patients still die of the original malignancy. The researchers were aware that early detection of residual microscopic disease would allow additional treatment to be administered, which may improve patient outcomes. In this study a new, more sensitive technique was applied to detect micrometastatic tumour cells. At time of primary surgery, bone marrow samples were collected from patients and examined using magnetic microspheres that recognise tumour cells. Clinical outcomes of patients was also assessed in the Outpatient Clinics and Rooms, including regular radiology. About 30% of patients were found to have micrometastatic cells present in their bone marrow. This result is about what the researchers would expect to find for the number of patients who succumb early to their original tumour. What is not yet known is whether these patients are the same as those who have micrometastases at the original surgery. This is because it takes an interval of about 5 disease-free years until a patient may be considered cured, however if their original tumour recurs, it would usually do so within 3 years. The researchers found that the detection of micrometastases in the bone marrow of patients at the time of surgery provides a more accurate assessment of their disease stage and may indicate a group of patients who should be considered for additional therapies. The researchers will continue to monitor the patients, and the more patients entered into the study, the more certain they can be about the result. If the technique proves promising, the next step will be to introduce chemotherapy to those who have positive bone marrow samples and follow their outcomes. The effect of a Chinese herbal medicine preparation (CH100) for the treatment of Hepatitis C Chief Investigators: Dr L Mollison, Ms L Totten Amount Awarded: $5,000.00 The Hepatitis C virus causes a long-lasting inflammation of the liver that can lead to cirrhosis of the liver over 20-30 years, with some cases ultimately developing liver cancer. Hepatitis C is contracted by contact with infected blood through injecting drug use, blood transfusions, tattooing, body piercing etc. Traditional Chinese Medicine is one of the world's oldest and most comprehensive systems of herbal medicine and combining this knowledge with modern science and research may lead to more effective treatments with fewer significant side effects. It is known that Hepatitis C sufferers turn to alternative treatments due to unsatisfactory results from conventional treatment and following initial promising results from a small trial, a larger trial of Chinese herbal medicine preparation was initiated. The herbal medicine CH100 is a combination of 19 ground Chinese herbs including liquorice, turmeric, rough gentian, locoweed, Mongolian dandelion, jujube berries, mugwort and fungi. Additional funding was granted by the Foundation to continue the promising work originally funded in 2000. Heart disease and oxidative stress Chief Investigators: Dr K Woollard, A/Prof K D Croft, Prof I B Puddey Amount Awarded: $9,760.00 Cardiovascular disease is one of the most common causes of death in Australia. There is growing evidence that oxidative stress - where the body's antioxidant defences cannot prevent damage by free radicals, or oxidants - contributes to plaque on the artery wall (athlerosclerotic plaque). This study sought to provide an understanding of the relationship between athlerosclerotic plaque and markers of oxidative stress and indicate the importance of treating this disease with antioxidant supplements. The researchers developed special tests to detect oxidative damage in human blood. Since direct evidence linking these markers of oxidation damage with heart disease is lacking, they studied subjects undergoing CT scan to determine the extent of heart disease to see if these factors are related. Subjects undergoing CT scanning of the heart had blood samples taken for analysis and also filled out a questionnaire about heart disease risk factors. Up to the time of submitting their research report, around 60 subjects had been studied and biochemical analysis of markers of oxidative damage had been completed for 32 subjects. The researchers found that markers of plasma oxidation damage were inversely related to the antioxidant capacity of blood. Interesting correlations are starting to emerge from the data however numbers are still too small to draw definite conclusions. Samples from the study will continue to be collected and analysed and will be a very valuable resource. Chronic stress and immune activity in elderly caregivers Chief Investigators: Dr I G Beckman, A/Prof D G Bruce Amount Awarded: $10,000.00 Aged caregivers appear to suffer more ill-health than elderly individuals not involved in full-time care. A recent study reported that elderly caregivers experiencing emotional strain have significantly higher mortality and morbidity rates compared to non carers and carers who were not experiencing stress. The underlying reasons for this, however, were not really not known. Moreover, given that this country has around 1 million carers who effectively contribute about $27 billion to the overall welfare budget, the researchers believed we need to know more about these "unsung community heroes". The research team asked some basic questions: (1) could they identify, using a simple test, those people with or at risk of developing chronic stress brought on as a result of their caring role and (2) link this stress marker with disturbances in immunological function, an important activity concerned with warding off infection and disease. They collected blood and saliva samples, and general health questionaires from 15 elderly caregivers (>60 years), 15 age and sex matched control subjects, and 15 young adults who had volunteered to participate in the study. The stress hormone cortisol was measured in saliva and immune mediators in blood. The team believed they identified a caring or stress effect that was associated with increased day to day changes in cortisol production. They also detected a fall in the capacity of caregivers to mount normal immune responses. These results provide a link between caring, chronic stress and immunological changes that may contribute to ill-health in the elderly which they hope will lead to better support for elderly caregivers. Do chemicals produced by bacteria cause important allergic diseases such as eczema and asthma? Chief Investigators: Dr DFJ Mallon, Dr DB McGechie Amount Awarded: $10,000.00 The bacteria Staphylococcal aureus is found in 90% of people with eczema, a risk factor for asthma and hay fever. The researchers looked to see if they could detect immune responses to proteins produced by Staphylococcal aureus in subjects with allergic diseases as well as eczema. The study involved adults with eczema, as well as healthy adults, and adults sensitised (positive skin tests) to allergens but who don't have symptoms. The researchers detected enhanced immune responses (likely to explain allergic disease) to Staphylococcal aureus proteins in subjects with eczema and asthma, compared to subjects without these diseases. This is a novel finding and implies that antibacterial agents may be useful in the treatment of these diseases.

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