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Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.
Cathcart, Mary-Clare Gately, Kathy Cummins, Robert Kay, Elaine O'Byrne, Kenneth J Pidgeon, Graham P
Cathcart, Mary-Clare
Gately, Kathy
Cummins, Robert
Kay, Elaine
O'Byrne, Kenneth J
Pidgeon, Graham P
Advisors
Editors
Other Contributors
Date
2011-03
Date Submitted
Keywords
Other Subjects
Subject 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
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
Planned Date
Start Date
Collaborators
Principal Investigators
Files
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21388528.pdf
Adobe PDF, 1.82 MB
Alternative Titles
Publisher
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.
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.
Language
en
ISSN
1476-4598
eISSN
ISBN
DOI
10.1186/1476-4598-10-25
PMID
21388528