Impaired IL-20 expression in lung cancer contributes to high levels of COX-2/PGE2 and angiogenesis

Nathalie Heuze-Vourc’h,Ming Liu, Harnisha Dalwadi, Felicita E. Baratelli,Li Zhu,Lee Goodglick, Jake Solomon, Lauren Winter, Mehis Pold,Ruben D. Ramirez,Jerry W. Shay,John D. Minna,Steven M. Dubinett

Cancer Research(2005)

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摘要
4642 >Background: Up-regulation of the inducible nitric oxide synthase (iNOS) and the cycloxygenase-2 enzyme (COX-2) have been reported to play a role in the process of carcinogenesis and angiogenesis. The aim of this study is to evaluate the possible correlation between iNOS, COX-2 and angiogenesis in ovarian serous carcinoma (OSC) Methods: We identified 118 patients with high-grade, advanced stage OSC from our database. Clinical data including patients’ and tumor characteristics and overall survival were collected. Two to 3 paraffin blocks were stained by immunohistochemistry (IHC) with antibodies to COX-2, VEGF and iNOS. For all three markers both intensity and percentage of positive cells were evaluated to give an overall score. Statistical analysis included Chi-square testing to evaluate the correlation between the various markers and the Kaplan-Meier method to evaluate survival Results: Up-regulation of all three markers was noted in a significant number of the cases. The frequencies of overexpression of the specific markers in the study population were: 49% for iNOS, 69% for COX-2 and 77% for VEGF. High iNOS expression strongly correlated with high expression of COX-2 and VEGF. In fact, 98.3% of tumors with high iNOS expression exhibited high COX-2 expression and 98.1% exhibited high VEGF expression. The median survival of patients with high iNOS expressing tumors was 637 days compared to 1107 days for those with low iNOS expressors; this difference did not reach statistical significance Conclusion: High expression of iNOS is noted in a significant number of OSC tumors. This high expression is associated with high expression of COX-2 and VEGF. This suggests a significant role for iNOS in the process of ovarian carcinogenesis and tumor angiogenesis and warrants further investigation
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