Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma

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dc.check.embargoformatNot applicableen
dc.check.infoNo embargo requireden
dc.check.opt-outNot applicableen
dc.check.reasonNo embargo requireden
dc.check.typeNo Embargo Required
dc.contributor.advisorBarry, Orla P.en
dc.contributor.advisorFanning, Liam J.en
dc.contributor.authorO'Callaghan, Carol
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2015-11-23T09:43:24Z
dc.date.available2015-11-23T09:43:24Z
dc.date.issued2015
dc.date.submitted2015
dc.description.abstractOesophageal cancer is an aggressive malignancy which is resistant to conventional therapy and has a poor prognosis. A greater understanding of the underlying molecular biology of oesophageal cancer and the identification of novel targets is necessary for the future treatment of this disease. This thesis focuses specifically on the ill-defined and understudied p38δ mitogen-activated protein kinase (MAPK) and its function(s) in oesophageal squamous cell carcinoma (OESCC). In contrast to the three other p38 isoforms (p38α, -β and –γ which have to-date been relatively well-studied), p38δ MAPK signalling is poorly understood. Thus, this research elucidates some of the role(s) played by p38δ MAPK in cancer progression. This work outlines how loss of p38δ MAPK expression confers greater tumourigenicity in oesophageal cancer. Restoration of p38δ MAPK expression, however, has anti-proliferative and anti-migratory effects and decreases OESCC capacity for anchorageindependent growth. Using a novel application of an enzyme-substrate fusion approach, the effect of phosphorylated p38δ (p-p38δ) MAPK expression is also considered. The work goes onto describe the effect(s) of p38δ MAPK status on the chemosensitivity of OESCC to conventional cisplatin and 5-fluorouracil (CF) versus the effectiveness of doxorubicin, cisplatin and 5-fluorouracil (ACF). ACF treatment of p38δ MAPK-negative OESCC results in decreased proliferation, migration and recovery, and increased apoptosis when compared with CF treatment. This thesis examines the potential mechanisms by which p38δ MAPK expression is lost in OESCC and identifies epigenetic regulation as the probable cause of differential p38δ MAPK expression. Also analysed is the role p38δ MAPK and p-p38δ MAPK play in the cell cycle. In summary, this research identifies p38δ MAPK as a possible molecular target and a potential predictor of response to chemotherapy in OESCC patients.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Callaghan, C. 2015. Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma. PhD Thesis, University College Cork.en
dc.identifier.endpage292
dc.identifier.urihttps://hdl.handle.net/10468/2082
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2015, Carol O'Callaghan.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectCanceren
dc.subjectOesophagealen
dc.subjectp38en
dc.subjectMAPKen
dc.thesis.opt-outfalse
dc.titleNovel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinomaen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Medicine and Health)en
ucc.workflow.supervisoro.barry@ucc.ie
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