Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

Hdl Handle:
http://hdl.handle.net/10147/128271
Title:
Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer
Authors:
Cathcart, Mary-Clare; Gately, Kathy; Cummins, Robert; Kay, Elaine; O' Byrne, Kenneth J; Pidgeon, Graham P
Citation:
Molecular Cancer. 2011 Mar 09;10(1):25
Issue Date:
9-Mar-2011
URI:
http://hdl.handle.net/10147/128271
Abstract:
Abstract Background Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease. Methods TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorCathcart, Mary-Clare-
dc.contributor.authorGately, Kathy-
dc.contributor.authorCummins, Robert-
dc.contributor.authorKay, Elaine-
dc.contributor.authorO' Byrne, Kenneth J-
dc.contributor.authorPidgeon, Graham P-
dc.date.accessioned2011-04-18T09:06:33Z-
dc.date.available2011-04-18T09:06:33Z-
dc.date.issued2011-03-09-
dc.identifierhttp://dx.doi.org/10.1186/1476-4598-10-25-
dc.identifier.citationMolecular Cancer. 2011 Mar 09;10(1):25-
dc.identifier.urihttp://hdl.handle.net/10147/128271-
dc.description.abstractAbstract Background Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease. Methods TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.-
dc.titleExamination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderCathcart et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2011-04-12T15:04:09Z-
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