How Do Bone-active Drugs Increase Patient Survival?
Funder
National Health and Medical Research Council
Funding Amount
$613,952.00
Summary
Bisphosphonates are a class of drugs used to prevent bone destruction in diseases such as osteoporosis. Evidence is emerging that these drugs also act on cells outside the skeleton to have additional beneficial effects, for example prolonging patient survival. This project will identify the cells affected and the mechanisms involved. With this knowledge, these drugs could be used more effectively and in different ways for the prevention or treatment of cancer and chronic human illnesses.
Macrophage Lineage Contribution To Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
When diagnosed early, breast cancer can be treated with a high degree of success. However, if the cancer spreads to other organs such as lungs and bone, patients suffer from severe pain and debilitating symptoms that often lead to death. Therapies for patients with advanced disease are extremely limited. It is the aim of this project to define the role that macrophages and stromal fibroblasts play in assisting the tumour cells to spread around the body and grow in other tissues.
Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers ar ....Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers are infected throughout an infected person's life and that they remain infected despite years of treatment with potent combination drug therapies which reduce the amount of virus in the blood to undetectable levels. We have evidence that suggests that a certain subset of monocytes may be preferentially infected with HIV and may contribute significantly to its persistence in the body. This subset is known to be expanded in response to certain infections, probably including HIV, and during inflammation. We have shown that these cells accumulate in the brains of HIV-infected people especially those with AIDS related dementia. In this project we will characterise these cells in the blood and test our hypothesis that ongoing infection in this subset of monocytes plays an important role in the course of HIV disease and contributes to the persistence of HIV infection and the failure of currently available therapies to eradicate it.Read moreRead less
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
Interactions Between HIV And Mycobacterial Infections Of Macrophages Mediated By Changes In Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$119,625.00
Summary
HIV-AIDS and tuberculosis are two of the worlds most important diseases. HIV-AIDS is the fourth leading killing disease worldwide and tuberculosis is the leading opportunistic infection in patients with AIDS particularly in the developing world. Both microbes infect the same cell type, the macrophage, which is widely distributed throughout the body, particularly in lymph nodes and lung. Recent studies in humans have shown that HIV and TB like organisms stimulate each others growth. This study us ....HIV-AIDS and tuberculosis are two of the worlds most important diseases. HIV-AIDS is the fourth leading killing disease worldwide and tuberculosis is the leading opportunistic infection in patients with AIDS particularly in the developing world. Both microbes infect the same cell type, the macrophage, which is widely distributed throughout the body, particularly in lymph nodes and lung. Recent studies in humans have shown that HIV and TB like organisms stimulate each others growth. This study uses the immense power of DNA microarrays, based on the identification of almost all genes by the human genome project, to decipher the interactions between the two microbes. By following up new leads indicated by the microarrays, the way in which the microbes manipulate the macrophage to enhance their own growth and that of the other can be eventually deciphered. This will provide new strategies for future interventions. New drugs are urgently needed for both microbes.Read moreRead less