The role of leukocyte, platelet and endothelial cell interactions in chemotherapy-induced venous thromboembolism (360G-Wellcome-200702_Z_16_Z)
Venous thromboembolism (VTE) is a life-threatening complication of cancer. Cancer patients undergoing chemotherapy are at increased risk of VTE, but the lack of in vitro models of VTE development has made it difficult to study the complex cell interactions involved in detail. Understanding the mechanisms that lead to VTE is the first step in designing safer anti-cancer chemotherapies for the future. I will investigate how the chemotherapy combination, CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone), increases VTE risk. I will determine the pro-thrombotic effects that these chemotherapy drugs have on leukocytes (particularly monocytes and neutrophils), platelets and endothelial cells, and how this is regulated by complex cell interactions. I will develop a new in vitro model of VTE that incorporates the key features of intact but activated endothelium cells, blood cells, including monocytes, neutrophils and platelets, and perfusion under venous flow and oxygenation. This model will be used to investigate the mechanisms of chemotherapy-induced VTE, the relative contribution of blood cell activation, endothelial cell activation, and the complex cell interactions involved. Together, this project will characterise the interactions between leukocytes, platelets and endothelial cells in response to CYMFP chemotherapy and increase our understanding of chemotherapy-induced VTE.
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Grant Details
Amount Awarded | 99591 |
Applicant Surname | Harper |
Approval Committee | Science Seeds Advisory Panel |
Award Date | 2015-12-14T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Seed Award in Science |
Internal ID | 200702/Z/16/Z |
Lead Applicant | Dr Matthew Harper |
Partnership Value | 99591 |
Planned Dates: End Date | 2018-07-01T00:00:00+00:00 |
Planned Dates: Start Date | 2016-07-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |