{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:50:07Z","timestamp":1790027407655,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T00:00:00Z","timestamp":1418169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["FIS 2011-02380"],"award-info":[{"award-number":["FIS 2011-02380"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"Abstract<\/jats:title>Prostacyclin (PGI2<\/jats:sub><\/jats:styled-content>) plays a role in cancer progression but the mechanism is currently poorly understood. Additionally, no data are available about the prognostic value of the PGI2<\/jats:sub><\/jats:styled-content> pathway in head and neck squamous cell carcinoma (HNSCC<\/jats:styled-content>) therapy. We evaluated the expression of the PGI2<\/jats:sub><\/jats:styled-content> pathway in HNSCC<\/jats:styled-content> patients. PGI2<\/jats:sub><\/jats:styled-content> production and PGI<\/jats:styled-content> synthase (PGIS<\/jats:styled-content>) expression, in terms of mRNA<\/jats:styled-content> (RT\u2010PCR<\/jats:styled-content>) and protein (immunoblotting), were lower in tumour samples than in non\u2010tumoural mucosa, whereas, as expected, COX<\/jats:styled-content>\u20102 expression was increased in HNSCC<\/jats:styled-content> tumour samples. Using local control of the tumour after radiotherapy or chemoradiotherapy as a dependent variable, patients were classified into two categories of PGIS<\/jats:styled-content> transcript levels. The high\u2010PGIS<\/jats:styled-content> group had a significantly lower frequency of local and distant failure than the low\u2010PGIS<\/jats:styled-content> group, and the 5\u2010year cancer\u2010specific survival was higher [90.2% (95% CI<\/jats:styled-content> 81.0\u201399.4%) versus 60.5% (95% CI<\/jats:styled-content> 44.4\u201376.6%)]. None of the four HNSCC<\/jats:styled-content> cell lines analysed expressed PGIS<\/jats:styled-content> and therefore they did not produce PGI2<\/jats:sub><\/jats:styled-content>. However, HNSCC<\/jats:styled-content>\u2010conditioned media enhanced PGI2<\/jats:sub><\/jats:styled-content> production in endothelial cells (ECs<\/jats:styled-content>). The stable analogue of PGI2<\/jats:sub><\/jats:styled-content>, carbaprostacyclin (cPGI2<\/jats:sub><\/jats:styled-content>), exerted little effect on HNSCC<\/jats:styled-content> cell line migration, and no effect on cell cycle distribution or proliferation rate after radiation injury was observed. Nevertheless, cPGI2<\/jats:sub><\/jats:styled-content> promoted EP<\/jats:styled-content>\u20104\u2010dependent in vitro<\/jats:italic> angiogenesis. Von Willebrand factor expression (EC<\/jats:styled-content> marker) and capillary density were significantly higher in the group of patients with high expression of PGIS<\/jats:styled-content>. Our results indicate that PGIS<\/jats:styled-content> expression was associated with radiotherapy efficiency. Although we do not provide direct evidence of a relationship between tumour vascularization and radiotherapy efficiency, our results suggest that the effect of PGI2<\/jats:sub><\/jats:styled-content> is related to its ability to promote vascularization. These results also support the concept that co\u2010adjuvant therapy with PGIS<\/jats:styled-content> enhancers, such as retinoids, could have therapeutic value for HNSCC<\/jats:styled-content> treatment. Copyright \u00a9 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4453","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T09:51:49Z","timestamp":1411638709000},"page":"125-135","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Prostacyclin\u2010synthase expression in head and neck carcinoma patients and its prognostic value in the response to radiotherapy"],"prefix":"10.1002","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-3294","authenticated-orcid":false,"given":"Mercedes","family":"Camacho","sequence":"first","affiliation":[{"name":"Laboratory of Angiology, Vascular Biology and Inflammation Institute of Biomedical Research (IIB Sant Pau) and Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenaida","family":"Pi\u00f1eiro","sequence":"additional","affiliation":[{"name":"Laboratory 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