Cyclooxygenase-2 expression predicts survival in malignant pleural mesothelioma

O’Kane, Sara L.; Cawkwell, Lynn; Campbell, A. M. G.; Lind, Michael

doi:10.1016/j.ejca.2005.04.019

Cited by 26 publications

(20 citation statements)

References 22 publications

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“…Various patients' characteristics have been studied for their potential effects on the survival of patients with MPM. Patients' age, histology, stage, PS, and therapeutic modality (e.g., EPP and/or chemotherapy) were identified as important predictors of prognosis in our study, consistent with previous reports by other investigators (33,34).…”

Section: Discussionsupporting

confidence: 83%

CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma

Aoe

Amatya

Fujimoto

et al. 2012

Clinical Cancer Research

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Purpose: Malignant pleural mesothelioma (MPM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells, without established indicators to predict responsiveness to chemotherapy.Experimental Design: Our study involving 79 MPM patients showed that 73.4% of MPM expressed CD26 on cell membrane.Results: The majority of epithelioid and biphasic types of MPM expressed CD26 on the cell membrane, whereas the sarcomatoid type showed a lack of CD26 surface expression. Although the sarcomatoid type was associated with poor prognosis (P < 0.0001), no significant relationship between CD26 expression and survival was observed. On the contrary, there was a trend for an association between response rate to chemotherapy and CD26 expression (P ¼ 0.053), with a higher level of CD26 expression more likely to be linked to better response to chemotherapy. Moreover, CD26 expression was a significant factor associated with improved survival in patients who received chemotherapy [median survival time (MST), 18.6 vs. 10.7 months, P ¼ 0.0083]. Furthermore, CD26 expression was significantly associated with better prognosis in patients receiving non-pemetrexed-containing regimens (MST, 14.2 vs. 7.4 months, P ¼ 0.0042), whereas there was no significant association between CD26 expression and survival time for patients receiving pemetrexed-containing regimens. Our in vitro and microarray studies showed that mesothelioma cells expressing high CD26 displayed high proliferative activity, and CD26 expression was closely linked to cell-cycle regulation, apoptosis, and chemotherapy resistance.Conclusions: Our results strongly suggest that CD26 is a clinically significant biomarker for predicting response to chemotherapy for MPM.

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Section: Discussionsupporting

confidence: 83%

CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma

Aoe

Amatya

Fujimoto

et al. 2012

Clinical Cancer Research

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“…However, the possibility of enhancing the cytotoxic effects of chemotherapeutic agents for mesothelioma through the addition of a COX-2 inhibitor has not been investigated. In MPM COX-2 has been shown to be overexpressed in 59-100% of tumour samples [20][21][22], suggesting that COX-2 may be a potential target for novel therapies for this disease. The COX-2 inhibitor celecoxib has previously been demonstrated to have a cytotoxic effect in malignant mesothelioma cell lines [23].…”

Section: Introductionmentioning

confidence: 99%

COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines

et al. 2010

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“…From the onset of symptoms, survival is a few weeks to a few years,3 median survival being 4–12 months in treated or untreated patients 4. Only a small number of patients (approximately 10%) survive more than 3 years, which seems to be restricted to the epithelioid subtype 5 6. Immunohistochemical analysis of Ki-67/MIB-1,7 p27 kip1 ,8 p21 cip1 and cyclooxygenase-25 9 have been correlated with survival in MPM, but their significance has not been entirely clarified.…”

mentioning

confidence: 99%

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors

Kothmaier

Quehenberger

Halbwedl

et al. 2008

Thorax

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Background: Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival ,3 years; STS) and long term survivors (survival .3 years; LTS) of MPM. Methods: 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology. Results: Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was upregulated in STS by signal transducer and activator of transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS. Conclusion: We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively.

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Cyclooxygenase-2 expression predicts survival in malignant pleural mesothelioma

Cited by 26 publications

References 22 publications

CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma

CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma

COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors

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