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
The Mechansim Of Cachexia Induced By The TGF-b Superfamily Cytokine, MIC-1
Funder
National Health and Medical Research Council
Funding Amount
$544,200.00
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 of cancer, wound - fracture healing and inflammation. Recent evidence also suggests it can act as an appetite suppressant, and this is especially relevant in conditons like cancer where it is overproduced. This project seeks to understand the mechanisms for its capacity to modify appetite
The Kynurenine Pathway Chemokines And MIC-1 In The Pathogenesis Of AIDS Dementia Complex.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
This proposal will examine the mechanisms by which HIV and other brain disorders such as encephalitis damage the brain. Further understanding of the biochemical pathway involved will lead to the possibility of novel drug therapy for these disorders.
Role Of The Novel TGF-b Superfamily Cytokine MIC-1 In The Pathogenesis And Treatment Of Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$309,536.00
Summary
Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important family of proteins that are involved in wound healing, development and inflammation. Our data thus far suggests that MIC-1 is an anti-inflammatory factor that is of particular relevance in rheumatoid arthritis. We wish to determine the relationship between the amount of this cytokine in the ....Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important family of proteins that are involved in wound healing, development and inflammation. Our data thus far suggests that MIC-1 is an anti-inflammatory factor that is of particular relevance in rheumatoid arthritis. We wish to determine the relationship between the amount of this cytokine in the joint and the blood and the activity of rheumatoid arthritis. To better understand the actions of this molecule, we also want to study the factors that regulate the production of MIC-1 from human blood cells. Finally, to assess whether MIC-1 is useful for the treatment of rheumatoid arthritis, we will use gene therapy approaches to develop animals that produce increased amounts of MIC-1 and determine whether this prevents or mitigates the development of rheumatoid arthritis.Read moreRead less
The In Vivo Biology Of The Novel TGF-b Superfamily Cytokine, MIC-1
Funder
National Health and Medical Research Council
Funding Amount
$280,430.00
Summary
Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important familty of proteins that are involved in wound healing, development and inflammation. Our data thus far suggest thatMIC-1 is an antiinflammatory factor that also involved in reproduction, especially in the health of the placenta. To determine the accuracy of these predictions we wish to use ....Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important familty of proteins that are involved in wound healing, development and inflammation. Our data thus far suggest thatMIC-1 is an antiinflammatory factor that also involved in reproduction, especially in the health of the placenta. To determine the accuracy of these predictions we wish to use genetic techniques to delete this gene from a mouse. Study of this genetically modified mouse will give us a great deal of information on the most important roles of MIC-1.Read moreRead less