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Title: Investigation of the mechanism of L-asparaginase-induced acute pancreatitis
Author: Peng, Shuang
ISNI:       0000 0004 6350 8792
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2017
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Intracellular Ca2+ and adenosine triphosphate (ATP) are the key elements needed for stimulant-evoked exocytotic enzyme secretion from pancreatic acinar cells. Physiological Ca2+ signals consist of repetitive spikes confined to the secretory granule region, which stimulate ATP production; whereas sustained global cytosolic Ca2+ elevations - toxic Ca2+ signals decrease ATP levels and cause necrosis leading to the inflammation of the pancreas - acute pancreatitis (AP), a life-threatening disease currently without specific therapy. The work presented in this thesis focuses on the mechanisms underlying the development of pancreatitis evoked by L-asparaginase and the potential ways to intervene asparaginase-associated pancreatitis (AAP). Asparaginase is an essential element of the chemotherapy regimen in the successful treatment of acute lymphoblastic leukaemia (ALL), the most common childhood cancer. But asparaginase treatment can lead to AAP, which is a side-effect of ALL treatment occurring in about 5–10% of cases. Following AP, further treatment with asparaginase is withheld to prevent recurrence of AP; however, withholding scheduled asparaginase is associated with a potential increase in ALL relapse. Understanding the pathogenesis of AAP could lead to effective therapies for this complication, potentially reducing toxicity and allowing re-exposure to continue treatment with asparaginase.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology ; R Medicine (General) ; RB Pathology