Macrophage inhibitory cytokine-1 (MIC-1) participates in cancer, stroke and heart attack. Studies show that measurement of MIC-1 in blood and cancer tissue might be useful to detect the development of cancer and determine whether it will spread. Also, MIC-1 measurement can identify people who are at risk of dying of cancer, heart attack and stroke. This study will show how MIC-1 may be used to prevent, diagnose and help treat these conditions and reduce healthcare costs.
We discovered, characterised and commercialised Macrophage inhibitory cytokine-1 (MIC-1/GDF15) for human therapy. Its blood level predicts death from cancer, heart attack/stroke and other diseases. This study will add important information for understandg the actions of this important protein
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
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.
The Role Of The TGF-b Superfamily Cytokine MIC-1 In Prostate Cancer Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
We have discovered that a protein called MIC-1 is strongly linked to prostate cancer and is made in large amounts by this tumor. There is a lot of circumstantial evidence that it is involved in the prostate cancer but the proof is missing. We propose to breed mice that are both prostate cancer prone and have genetically modified MIC-1 : mice either are unable to make MIC-1 , or make it in large amounts. We will determine how MIC-1 affects prostate cancer development.
A Lineage Specific Pathway For Progression Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$485,746.00
Summary
Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastas ....Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastasis of melanoma. These markers could serve as an important diagnostic marker for melanoma. Further, they may be suitable drug targets for the prevention and treatment of metastatic melanoma, and will advance our understanding of how melanoma spreads.Read moreRead less
The Role Of The TGF-b Superfamily Cytokine MIC-1 In The Pathogenesis Of Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$348,950.00
Summary
MIC-1 is a protein first cloned and characterised by our research group. It belongs to the TGF beta protein superfamily which is very important in development, cancer, wound - fracture healing and inflammation. The aim of this project was to start to gain an understanding of the role of this protein, both in normal biological processes (especially pregnancy) and in disease. MIC-1 is present in the blood of all individuals and high levels are associated with an increased risk of heart attacks and ....MIC-1 is a protein first cloned and characterised by our research group. It belongs to the TGF beta protein superfamily which is very important in development, cancer, wound - fracture healing and inflammation. The aim of this project was to start to gain an understanding of the role of this protein, both in normal biological processes (especially pregnancy) and in disease. MIC-1 is present in the blood of all individuals and high levels are associated with an increased risk of heart attacks and strokes. In this study we wish to use animal models, in which the gene for MIC-1 has either been deleted or enhanced, to determine whether MIIC-1 plays a direct role in these diseases.Read moreRead less
The Role Of MIC-1 In The Promotion And Progression Of Skin Squamous Cell Carcinoma.
Funder
National Health and Medical Research Council
Funding Amount
$237,258.00
Summary
Skin cancers are the most common human tumours and the incidence is increasing. Ultra-violet (UV) light is the main factor in the formation of skin cancer. This project will find how a gene product (MIC-1) induced by solar UV affects the skin, and why we see it in skin cancers. This protein has other interesting properties that could bear directly on measuring sun exposure and understanding skin cancer. A processed form is released into the blood, where it could carry UV signals and be used in p ....Skin cancers are the most common human tumours and the incidence is increasing. Ultra-violet (UV) light is the main factor in the formation of skin cancer. This project will find how a gene product (MIC-1) induced by solar UV affects the skin, and why we see it in skin cancers. This protein has other interesting properties that could bear directly on measuring sun exposure and understanding skin cancer. A processed form is released into the blood, where it could carry UV signals and be used in population studies as a measure of sun exposure. It's also induced by certain cancer-promoting chemicals which resemble UV light in their immediate effects. A lot could therefore be learnt from this protein, and if we find that MIC-1 promotes the growth of normal and tumour cells in the skin after UV exposure, we can look for ways to stop this happening.Read moreRead less
MODULATING MIC-1 CYTOKINE BIOAVAILABILITY: IMPACT ON TUMOUR BIOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$341,210.00
Summary
MIC-1 cytokine is secreted by many tumour cells. It is commonly secreted as an inactive precursor form of MIC-1 which binds to the extracellular matrix surrounding cells, via its propeptide. This creates latent stores of cytokine which can be released and activated under specific conditions. The propeptide controls the balance between latent stores of inactive MIC-1 precursor and soluble forms of mature bioactive cytokine, which can act on surrounding cells or move into the circulation. The sign ....MIC-1 cytokine is secreted by many tumour cells. It is commonly secreted as an inactive precursor form of MIC-1 which binds to the extracellular matrix surrounding cells, via its propeptide. This creates latent stores of cytokine which can be released and activated under specific conditions. The propeptide controls the balance between latent stores of inactive MIC-1 precursor and soluble forms of mature bioactive cytokine, which can act on surrounding cells or move into the circulation. The significance of these latent stores is underscored by the finding that the level of these stores correlates with prostate cancer outcome, and also that very high circulating levels of active MIC-1 cytokine in the blood, leads to the massive weight loss characteristic of a syndrome called cancer cachexia. This is common in late stages of cancer and is a major contributing factor to the death of cancer patients. Understanding the mechanisms by which latent MIC-1 stromal stores are created and regulated, as well as their role in tumourigenesis, will have major impact on our understanding of the role of this cytokine in cancer. This is essential in order to adequately harness that knowledge for the benefit of patients.Read moreRead less