E-Thesis 186 views 50 downloads
Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease / Hamsa Naser
Swansea University Author: Hamsa Naser
DOI (Published version): 10.23889/SUthesis.67287
Abstract
Multiple myeloma is a type of blood cancer originating in the plasma cells of the bone marrow, affecting over 6,000 individuals in the UK annually. As a haematological malignancy, its incidence has increased by 11% in the UK over the past decade, making it the 19th most common cancer in the region....
| Published: |
Swansea, Wales, UK
2024
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | Ph.D |
| Supervisor: | Thornton, Cathy ; Cronin, James |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa67287 |
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| Abstract: |
Multiple myeloma is a type of blood cancer originating in the plasma cells of the bone marrow, affecting over 6,000 individuals in the UK annually. As a haematological malignancy, its incidence has increased by 11% in the UK over the past decade, making it the 19th most common cancer in the region. Myeloma bone disease, a severe complication of multiple myeloma, impacts more than 80% of patients, leading to osteolytic lesions, pain, mobility issues, fractures, and neurological deficits. Although not classified as bone cancer, myeloma significantly affects bone health. Current treatments for myeloma bone disease focus on pain management, surgical fracture repair, and radiation therapy to shrink bone lesions, with most therapies aimed at controlling and reducing bone pain. Preventive treatments are needed to mitigate the risk of developing myeloma bone disease. Direct interactions between myeloma cells and osteoclasts have been shown to increase myeloma cell proliferation and osteoclastic differentiation. This study employs an in vitro osteoclast model to explore the mechanisms of osteoclast differentiation and activation. The model serves as a valuable tool for investigating the effects of current myeloma therapies, such as immunomodulatory imide drugs, and for examining potential new treatments like interleukin-4, -10, and -13. The study showcases the use of various endpoint techniques and the development of real-time cell analysis systems to monitor osteoclast differentiation and fusion. Additionally, it demonstrates the application of impedance and clustering to further investigate these changes in response to treatments. The research provides insights into the differences between peripheral blood and bone marrow-derived mononuclear cells and examines the impact of immunomodulatory imide drugs and interleukins-4, -10, and -13 on the production of pro-inflammatory cytokines by these cells. |
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| Keywords: |
Multiple myeloma, blood cancer, plasma cells, bone marrow, haematological malignancy, myeloma bone disease, osteolytic lesions, osteoclasts, immunomodulatory imide drugs, interleukin-4, interleukin-10, interleukin-13, real-time cell analysis, impedance, clustering, peripheral blood, pro-inflammatory cytokines |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Swansea Myeloma Fund |