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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....

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Published: Swansea, Wales, UK 2024
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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spelling v2 67287 2024-08-01 Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease 29b4023fc506f38e5d235994a50d4471 Hamsa Naser Hamsa Naser true false 2024-08-01 MEDS 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. E-Thesis Swansea, Wales, UK 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 29 7 2024 2024-07-29 10.23889/SUthesis.67287 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Thornton, Cathy ; Cronin, James Doctoral Ph.D Swansea Myeloma Fund Swansea Myeloma Fund 2024-08-01T17:08:37.7458707 2024-08-01T16:42:36.7631562 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Hamsa Naser 1 67287__31036__a073a5245cb6499eaa1d64d54454cf13.pdf Naser_Hamsa_PhD_Thesis_Final_Redacted_Signature.pdf 2024-08-01T17:03:11.7217875 Output 80197667 application/pdf E-Thesis – open access true Copyright: The Author, Hamsa Naser, 2024. true eng
title Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease
spellingShingle Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease
Hamsa Naser
title_short Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease
title_full Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease
title_fullStr Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease
title_full_unstemmed Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease
title_sort Monocyte-Derived Osteoclasts as a Platform for Investigating Standard and Novel Treatments for Multiple Myeloma Bone Disease
author_id_str_mv 29b4023fc506f38e5d235994a50d4471
author_id_fullname_str_mv 29b4023fc506f38e5d235994a50d4471_***_Hamsa Naser
author Hamsa Naser
author2 Hamsa Naser
format E-Thesis
publishDate 2024
institution Swansea University
doi_str_mv 10.23889/SUthesis.67287
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
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description 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.
published_date 2024-07-29T17:08:37Z
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score 11.037603

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