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

Hdl Handle:
http://hdl.handle.net/10147/138738
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
Affiliation:
Department of Surgery, Institute of Molecular Medicine, Trinity Health Sciences Centre, St. James's Hospital, Dublin 8, Ireland.
Citation:
Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer. 2011, 10:25 Mol. Cancer
Journal:
Molecular cancer
Issue Date:
Mar-2011
URI:
http://hdl.handle.net/10147/138738
DOI:
10.1186/1476-4598-10-25
PubMed ID:
21388528
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/21388528
Abstract:
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.; 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.; 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.; 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:
Article
Language:
en
MeSH:
Adenocarcinoma; Apoptosis; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Enzyme Inhibitors; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung Neoplasms; Male; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Thromboxane B2; Thromboxane-A Synthase; Tissue Array Analysis
ISSN:
1476-4598

Full metadata record

DC FieldValue Language
dc.contributor.authorCathcart, Mary-Clareen
dc.contributor.authorGately, Kathyen
dc.contributor.authorCummins, Roberten
dc.contributor.authorKay, Elaineen
dc.contributor.authorO'Byrne, Kenneth Jen
dc.contributor.authorPidgeon, Graham Pen
dc.date.accessioned2011-08-03T14:55:13Z-
dc.date.available2011-08-03T14:55:13Z-
dc.date.issued2011-03-
dc.identifier.citationExamination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer. 2011, 10:25 Mol. Canceren
dc.identifier.issn1476-4598-
dc.identifier.pmid21388528-
dc.identifier.doi10.1186/1476-4598-10-25-
dc.identifier.urihttp://hdl.handle.net/10147/138738-
dc.description.abstractThromboxane 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.-
dc.description.abstractTXS 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.-
dc.description.abstractTXS 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.-
dc.description.abstractTXS 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.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/21388528en
dc.subject.meshAdenocarcinoma-
dc.subject.meshApoptosis-
dc.subject.meshBlotting, Western-
dc.subject.meshCarcinoma, Non-Small-Cell Lung-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Proliferation-
dc.subject.meshCyclooxygenase 2-
dc.subject.meshEnzyme Inhibitors-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation, Enzymologic-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshPrognosis-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshThromboxane B2-
dc.subject.meshThromboxane-A Synthase-
dc.subject.meshTissue Array Analysis-
dc.titleExamination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Institute of Molecular Medicine, Trinity Health Sciences Centre, St. James's Hospital, Dublin 8, Ireland.en
dc.identifier.journalMolecular canceren
dc.description.provinceLeinster-

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.