The Effects Of Zoledronic Acid On Bone Architecture In Premenopausal Women With Breast Cancer Receiving Adjuvant Combined Ovarian Suppression And Aromatase Inhibitor Therapy: A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
In premenopausal women, a new treatment method that reduces oestrogen levels to almost zero significantly reduces the risk of breast cancer recurrence. However, this is likely to cause substantial bone loss leading to fractures. Using a new imaging technique (HR-pQCT), the effects of profound oestrogen deprivation on bone structure in premenopausal women will be studied. The ability of zoledronic acid, a drug that reduces bone loss, to prevent these adverse bone effects will also be examined.
Bone Growth For Healthy Development: Physiology, Pathophysiology, And Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Musculoskeletal damage is a major burden on individuals and our health care system. My research program will focus on improving bone health in three important areas: (1) children’s growth plate injury and growth defects; (2) bone loss and bone marrow defects from cancer chemotherapy; (3) ensuring that bone grows healthily in early life. The overall intent of this research is to develop new therapies when bone doesn’t grow well, or is damaged.
The Role Of Hyaluronic Acid, CD44 And Osteopontin In Haemopoietic Stem Cell Biology
Funder
National Health and Medical Research Council
Funding Amount
$472,062.00
Summary
Marrow and microenvironmental cell (MC) interactions play a central role in bone marrow (BM) cell localisation and regulation. Specifically, the regulation of primitive blood cells (HSC) is affected by their locality and their expression of a wide repertoire of cell adhesion molecules. This project is based upon the unique observations made in the applicants laboratory demonstrating that the three molecules hyaluronic acid (HA), CD44 and osteopontin play key roles in the localisation of HSC with ....Marrow and microenvironmental cell (MC) interactions play a central role in bone marrow (BM) cell localisation and regulation. Specifically, the regulation of primitive blood cells (HSC) is affected by their locality and their expression of a wide repertoire of cell adhesion molecules. This project is based upon the unique observations made in the applicants laboratory demonstrating that the three molecules hyaluronic acid (HA), CD44 and osteopontin play key roles in the localisation of HSC within the BM following transplantation and in regulating their development into mature blood cells. Encapsulating the concept of highly specific, local interactions regulating blood cells is the 'niche' hypothesis in which MC form a specific 'niche'. The current inability to identify HSC in situ makes it impossible to analyse either their distribution or molecules that regulate this process. Circumstantial evidence suggests the presence of HSC 'niches' in close association with the bone. Using a novel approach based on BM transplantation to track cells lodging in the BM, we were the first to report that the lodgement of a transplanted HSC is not a random process, but results in cells of donor origin migrating to the bone-marrow interface. The presence of HA and CD44 on the HSC and CD44 and ostepontin in the marrow microenvironment are critical for this pattern of lodgement. In addition, we now have evidence that HA and osteopontin are important in the maintenance of HSC in their primitive state. This proposal aims to confirm the critical roles and interactions of these three molecules in HSC biology.Read moreRead less
Histone Deacetylase Inhibitors (HDIs) With Antineoplastic And Antiosteolytic Properties
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Metastatic bone disease is very common in patients with many forms of solid tumours. Our approach to use Histone Deacetylase Inhibitors (HDIs), to target bone metastases offers an exciting therapeutic potential. Treatment with HDIs will have the potential to suppress cancer-induced bone destruction by integrating the cytotoxic and osteotropic properties that reside within the same compound. Our preclinical data will facilitate the translation of HDIs to clinical trials for bone cancer.
Osteosarcoma is the most common cancer of bone. It osurs most frequently in childhood (teenage years) and current therapy is limited to surgery and chemotherapy. We have developed a new model of osteosarcoma that displays a high degree of similarity to human osteosarcoma. We aim to further understand this model and apply these findings to help treat human osteosarcoma.
Effects Of Ephrin-Eph And PTHrP Signalling On Osteosarcoma.
Funder
National Health and Medical Research Council
Funding Amount
$646,486.00
Summary
Osteosarcoma (OS) is the most common bone cancer in children, with ~170 cases per year in Australia. We used genetic mutation of mice to induce OS that is very similar to human OS. The OS produces parathyroid hormone-related protein and ephrins and responds to both proteins. We will study how the cancer develops and spreads, and how this is affected by these two pathways, both of which are implicated in cancer development, and could be targets for treatment.
Hypothalamic Signalling In Cortical And Trabecular Bone Anabolic Activity
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but the ....Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but these are limited by expense and safety concerns. We have discovered a pathway in the brain that reduces bone formation and by blocking this pathway we can achieve doubling of the amount of bone in key bone sites. This occurs due to a marked increase in the amount of new bone formed. In fact, genetic manipulation of this pathway was able to double the speed at which bone is made by the skeleton. Excitingly, these increases in bone were possible in adult mice, suggesting such changes could be potential therapy for human patients. However, in order to be able to harness this pathway we must understand what molecules within the brain are responsible for the signals that reach the bone. Our proposal aims to identify the nerve signalling molecule(s) and the receptor for these signals within the brain that initiates the increase in bone formation. This project ultimately aims to identify a target for new therapies that could cause this beneficial effect by administration of a simple treatment, preferably by mouth in adult humans.Read moreRead less
The Molecular Mechanisms Controlling Maintenance Of Osteogenic Precursor Cells And Skeletal Tissue Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bon ....Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bone resorption by osteoclasts, but may also occur through a decline in the number of bone forming cells called osteoblasts or their progenitors. Fracture non-union, prosthetic loosening and the replacement of large defects in bone are common and difficult problems. The use of autologous bone cells generated from isolated BMSSCs in combination with bio-compatible implant materials would provide a novel solution for the treatment of these problems, avoiding the use of autografts and allografts of bone with all their associated difficulties. However, large numbers of ex vivo expanded BMSSCs are currently required to heal even small bone defects in animal models. This is compounded by the decline in proliferation rates and bone forming capacity of BMSSCs during prolonged expansion in culture. An improved understanding of the genes that regulate the proliferation and differentiation of BMSSCs in vitro is therefore an essential prerequisite for the effective management of bone fracture and bone loss. We propose to genetically manipulate the expression of genes in BMSSCs, that are known to regulate cellular growth and development inorder to maintain the growth of stem cell populations in vitro and to extend their capacity to form bone when transplanted in vivo.Read moreRead less
I am a hematologist with expertise in the science of immunology and clinical experience in bone marrow transplantation and the treatment of hematological malignancies. My vision is to study the biology of dendritic cells, which are the specialized white cells that initiate the immune response, and then, to apply this knowledge to the design and introduction of novel diagnostic and therapeutic immune strategies, to improve the survival of patients with leukemia, lymphoma and multiple myeloma.
Understanding The Pharmacology Of G-CSF For Treating Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$429,393.00
Summary
Heart attacks remain the most common cause of heart failure. Unlike many other tissues the heart is unable to repair itself. Recently it has been recognised that bone marrow cells promote to a small degree repair. Our research confirms these findings and indicates that these can be affected by substances that increase the circulating bone marrow cell numbers. This project will explore how bone marrow cells improve repair and ways to further improve efficacy.