Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-c and lymph node metastasis in human oral tongue cancer

Morita, Yoshihiro; Morita, Nobuo; Hata, Kenji; Nakanishi, Masayoshi; Kimoto, Natsuko; Omata, Tetsuji; Nakamura, Yasushi; Yoneda, Toshiyuki

doi:10.1016/j.oooo.2013.12.410

Cited by 21 publications

(27 citation statements)

References 42 publications

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“…As regards VEGFs, the results were mixed with a very wide CI for HR from the random effects model. However, two of the VEGFs studies analysed VEGF-A and one VEGF-C. A positive or high VEGF-C value was shown to be associated with an improved prognosis ( Morita et al , 2014 ), which was in sharp contrast with the two other studies analysing the expression of VEGF-A, both indicating a much worse survival for a positive VEGF-A value. When the VEGF-C study was excluded from the meta-analysis, the pooled estimate for HR was 7.34 (95% CI from 2.32 to 23.22), which provides rather strong evidence for VEGF-A being a useful prognostic biomarker.…”

Section: Resultsmentioning

confidence: 74%

Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis

et al. 2017

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Background:Identifying informative prognostic biomarkers for oral tongue squamous cell carcinoma (OTSCC) is of great importance in order to better predict tumour behaviour and to guide treatment planning. Here, we summarise existing evidence regarding immunohistochemical prognostic biomarkers for OTSCC.Methods:A systematic search of the literature was performed using the databases of Scopus, Ovid Medline, Web of Science and Cochrane Library. All studies which had investigated the prognostic significance of immunohistochemical biomarkers in OTSCC during the period from 1985 to 2015 were retrieved. For the five most often evaluated biomarkers a random-effects meta-analysis on overall survival was performed, including those studies that provided the necessary statistical results.Results:A total of 174 studies conducted during the last three decades were found, and in these 184 biomarkers were evaluated for the prognostication of OTSCC. The five biomarkers most frequently assessed were p53, Ki-67, p16, VEGFs and cyclin D1. In the meta-analyses, the most promising results of the prognostic power for OTSCC were obtained for cyclin D1. For studies of VEGF A and C the results were equivocal, but the pooled analysis of VEGF A separately showed it to be a useful prognosticator for OTSCC. There was no sufficient evidence to support p53, Ki-67 and p16 as prognostic biomarkers for OTSCC. Limitations in the quality of the published studies (e.g., small cohorts, lack of compliance with REMARK guidelines) are widespread.Conclusions:Numerous biomarkers have been presented as useful prognosticators for OTSCC, but the quality of the conduct and reporting of original studies is overall unsatisfactory which does not allow reliable conclusions. The value of two biomarkers (VEGF-A and cyclin D1) should be validated in a multicentre study setting following REMARK guidelines.

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Section: Resultsmentioning

confidence: 74%

Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis

et al. 2017

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“…4A-C, nimesulide abolished the promoting effects of miR-26b inhibition on the proliferation, migration and invasion in SCC-4 cells, suggested the critical role of COX-2 in miR-26b-regulated oncogenesis (P<0.05). Previous studies revealed that COX-2 could promote the proliferation and metastasis of human tongue squamous cell carcinoma cells through the VEGF-C pathway (21)(22)(23)(24)(25). In the present study, we investigated the expression changes of VEGF-C in SCC-4 cells by western blot analysis.…”

Section: Cox-2 Is the Direct Functional Target Of Mir-26bmentioning

confidence: 84%

miR-26b is downregulated in human tongue squamous cell carcinoma and regulates cell proliferation and metastasis through a COX-2-dependent mechanism

et al. 2014

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MicroRNAs (miRNAs) are important gene regulators that play a profound role in tumorigenesis. Previous studies have revealed that miR-26b is downregulated in a wide range of malignant tumors and plays an important role in the regulation of carcinogenesis and tumor progression. In the present study, we revealed that miR-26b expression was decreased in human tongue squamous cell carcinoma and was associated with clinical stage, lymph node metastasis and survival prognosis. Ectopic expression of miR-26b suppressed the proliferation and metastasis of human tongue squamous cell carcinoma cells. Using a luciferase reporter assay, combined with western blot analysis results, we identified PTGS2 (prostaglandin-endoperoxide synthase-2, encoding COX-2) as the functional target of miR-26b. Specific inhibition of COX-2 activity by nimesulide further confirmed that miR-26b was able to regulate the cell proliferation and metastasis of the human tongue squamous cell carcinoma cells through a COX-2-dependent mechanism. Taken together, these results suggest that miR-26b serves as a tumor suppressor by targeting COX-2 and calls for the use of miR-26b as a potential therapeutic tool for human tongue squamous cell carcinoma, where COX-2 is often hyperactivated.

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“…It follows therefore that in tumor types where analysis of COX-2 expression across tumor samples was not informative in terms of prognosis, its correlation with VEGF expression produced a statistically significant prognostic measure. Other informative COX-2-VEGF correlative relationships were found in cancer of the tongue, in which COX-2 and VEGF coexpression correlated with lymphangiogenesis and lymph node metastases [47]; in oral squamous cell carcinoma where VEGF-C was associated with promoting peri-tumoral lymphangiogenesis [37], in classical Hodgkin's lymphoma where both factors correlated with angiogenesis and tumor progression [36], and in esophageal adenocarcinoma, where COX-2 and VEGF were found to be independently associated with a poor prognosis [43].…”

Section: Cox-2 Expression In Cancermentioning

confidence: 96%

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Hugo

Saunders

Ramsay

et al. 2015

J Mammary Gland Biol Neoplasia

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The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

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Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-c and lymph node metastasis in human oral tongue cancer

Cited by 21 publications

References 42 publications

Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis

Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis

miR-26b is downregulated in human tongue squamous cell carcinoma and regulates cell proliferation and metastasis through a COX-2-dependent mechanism

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

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