Prelim Study Of Association Between Nutritional Indices, Psychosocial Factors, Cytokines & Survival Advanced Cancer Pati
Funder
National Health and Medical Research Council
Funding Amount
$24,820.00
Summary
This preliminary project aims to evaluate associations between cancer cachexia, psychosocial factors and cytokine levels in blood. The final decline of most patients with advanced cancer is associated with the cancer cachexia syndrome, triggered in part by cytokine release. Measuring cytokines may enable identification of patients about to enter this final stage. Further, factors like mood and social support appear to alter cytokine levels. The associations established by this study may point to ....This preliminary project aims to evaluate associations between cancer cachexia, psychosocial factors and cytokine levels in blood. The final decline of most patients with advanced cancer is associated with the cancer cachexia syndrome, triggered in part by cytokine release. Measuring cytokines may enable identification of patients about to enter this final stage. Further, factors like mood and social support appear to alter cytokine levels. The associations established by this study may point to treatment options that can delay the terminal phase while improving quality of life.Read moreRead less
Characterisation Of The Molecular Pathogenesis Of Cancer Cachexia Syndrome In Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$100,381.00
Summary
Cachexia is a hypermetabolic wasting syndrome involving depletion of both fat and muscle which affects 80% of cancer patients. The exact mechanisms of this syndrome are unknown at the molecular level and this affects our ability to predict, prevent or treat this problem. This study aims to elucidate the molecular mechanisms of cancer cachexia syndrome with a view to implementing nutritional, exercise and pharmacological interventions to prevent its onset.
Nutrition And Rehabilitation In Advanced Cancer Patients
Funder
National Health and Medical Research Council
Funding Amount
$225,991.00
Summary
This preliminary project aims to evaluate associations between cancer cachexia, psychosocial factors and cytokine levels in blood. The final decline of most patients with advanced cancer is associated with the cancer cachexia syndrome, triggered in part by cytokine release. Measuring cytokines may enable identification of patients about to enter this final stage. Further, factors like mood and social support appear to alter cytokine levels. The associations established by this study may point to ....This preliminary project aims to evaluate associations between cancer cachexia, psychosocial factors and cytokine levels in blood. The final decline of most patients with advanced cancer is associated with the cancer cachexia syndrome, triggered in part by cytokine release. Measuring cytokines may enable identification of patients about to enter this final stage. Further, factors like mood and social support appear to alter cytokine levels. The associations established by this study may point to treatment options that can delay the terminal phase while improving quality of life.Read moreRead less
Cancer cachexia is a devastating disease characterised by skeletal muscle wasting and weakness. It impairs patient quality of life and accounts for >20% of cancer-related deaths. My work aims to identify factors contributing to the development of cancer cachexia. This insight will then enable me to test potential strategies to prevent the wasting seen in cancer patients to improve their quality of life and to reduce mortality.
Development Of A Humanised Antibody To MIC-1/GDF15 For Therapy Of Anorexia/cachexia Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$587,349.00
Summary
Severe starvation and weight loss (cachexia) is a complication that affects about one quarter of cancer patients. In many this is due to the cancer producing a powerfula appetite suppressive protein called MIC-1/GDF15. This weight loss can be prevented by blocking the protein with an antibody drug. We have already shown that we can treat mice in this way by using a mouse antibody. We now aim to engineer these antibodies by making them more human-like. This will allow us to treat weight loss in h ....Severe starvation and weight loss (cachexia) is a complication that affects about one quarter of cancer patients. In many this is due to the cancer producing a powerfula appetite suppressive protein called MIC-1/GDF15. This weight loss can be prevented by blocking the protein with an antibody drug. We have already shown that we can treat mice in this way by using a mouse antibody. We now aim to engineer these antibodies by making them more human-like. This will allow us to treat weight loss in human cancer patients.Read moreRead less
Cytokine Secretion: A Model For Protein Trafficking.
Funder
National Health and Medical Research Council
Funding Amount
$204,111.00
Summary
TNF-a is an inflammatory cytokine with important roles in host defense, tumour regulation and energy homeostatis, however the oversecretion of TNF-a is also a major cause of septic shock, rheumatoid arthritis, Chron?s disease and the cachexia of cancer. TNF-a synthesis and its release from the surface of cells are relatively well understood. However little is known about its trafficking through the secretory pathway of cells. Understanding this process has the potential to provide new ways of co ....TNF-a is an inflammatory cytokine with important roles in host defense, tumour regulation and energy homeostatis, however the oversecretion of TNF-a is also a major cause of septic shock, rheumatoid arthritis, Chron?s disease and the cachexia of cancer. TNF-a synthesis and its release from the surface of cells are relatively well understood. However little is known about its trafficking through the secretory pathway of cells. Understanding this process has the potential to provide new ways of controlling the secretion of TNF-a. In previous work we have characterized transport vesicles and cytoskeletal proteins involved in secretory pathways of epithelial cells. We now propose to focus on the characterization of transport vesicles, and the roles of actin and myosins involved in TNF-a secretion in macrophages. These studies will rely on introducing new technology to this line of research. Fluorescent tagged constructs of TNF-a will be expressed and viewed in living cells to analyse the secretory pathway and measure the transport of TNF-a from its site of accumulation in the Golgi complex to the cell surface. This work aims to identify membrane-bound vesicles and vesicle-associated proteins that target TNF-a for secretion. We will begin to investigate the role of actin and myosins, using drugs and microinjected peptides to block their function. Overall these studies will provide important cell biological information about protein trafficking in cells. Cytokine secretion is important in immunity and cancer, information important to both fields will be gained from these studies.Read moreRead less
Body Composition Changes In Cardiac Cachexia: Pathophysiology, Quantification And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$120,000.00
Summary
Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an exam ....Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an examination of the effects of exercise on measures of cachexia in patients with congestive heart failure. The researchers believe that this study will supply valuable new information about the development of cachexia and lead to new therapies for this syndrome.Read moreRead less
Cancer Anorexia/cachexia: Mechanisms For Anorexia And Appetite Regulation By Tumour Derived MIC-1/GDF15
Funder
National Health and Medical Research Council
Funding Amount
$643,060.00
Summary
We have recently discovered that MIC-1 is a new appetite suppressive agent which when overproduced in some diseases like cancer, causes severe weight loss. This project sets out to determine the mechanisms it employs in regulation of appetite centres in the brain.
Cachexia is a major side effect of cancer, resulting in significant muscle wasting, fat loss and organ failure. Up to 80% of cancer patients suffer and 25% succumb to this condition. This significantly affects the treatment regimens of cancer patients and affects their quality of life. We have developed monoclonal antibodies that block and reverse cachexia in preclinical mouse cancer models. Our aims are to humanise the antibody and manufacture it for the first clinical trial in humans.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.