Molecular and cellular mechanisms of skeletal disease mediated by plasma cell dyscrasias

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/298935

Funding Status
Closed

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Funded Activity Summary

Osteolytic and osteosclerotic lesions of bone are common sequelae of primary and secondary bone cancers, including cancers of hematological origin. There is now strong evidence that tumor cells perturb the local balance between bone resorption and formation, and in cases of osteolysis, cause increased osteoclast (OC)-mediated bone resorption without a matching amount of bone formation. This proposal arises from our extensive clinical and basic science experience with multiple myeloma (MM) in addition to other skeletal tumors, and our strong background in both OC and osteoblast biology. MM is a hematological malignancy characterised by plasma cell dyscrasia, which typically causes progressive and severe destruction of the skeleton, with accompanying bone pain, fracture and finally, hypercalcaemia of malignancy. Two related diseases, MGUS and POEMS, have been chosen for study because of their key similarities and differences with MM, and are likely to shed new light on the activities of MM in the bone. MGUS does not cause identifiable bone defects, whereas POEMS can give rise to both osteolytic and osteosclerotic lesions. Comparison of these conditions will uniquely enable us to examine why these seemingly related neoplasms are able to mediate disparate skeletal disease states. Primarily, and since there are few curative therapies for MM at present, our proposed studies are designed to identify targets for therapy that will treat the most serious manifestation of this disease, namely its destruction of bone tissue.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $432,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Haematology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

aberrant bone remodelling | cancer cell-mediated osteolysis | cancer cell-mediated osteosclerosis | cytokine activation of osteoblast and osteoclast function | haematological cancer which is metastatic to bone | haematological malignancy | orthopaedic osteolysis | osteosclerotic and osteolytic bone disease

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