| Interrelated overexpression of endothelial and inducible nitric oxide synthases, endothelin-1 and angiogenic factors in human papillary thyroid carcinoma. | |
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MedLine Citation:
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PMID: 16712675 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Nitric oxide (NO) and endothelin-1 (ET-1) are involved in carcinogenesis. Overexpression of the ET-1 axis has been demonstrated in papillary thyroid carcinoma (PTC). This study investigated the expression of NO synthases (NOS) and their relationship with expression of ET-1 and angiogenic markers in PTC. DESIGN AND PATIENTS: Expression of NOS, angiogenic markers [vascular endothelial growth factor (VEGF), angiopoietin-1 and angiopoietin-2] and their receptors was studied in surgical thyroid samples obtained from 22 patients aged 15-68 years. Three groups were constituted: normal thyroid (n = 5), Hashimoto's thyroiditis (n = 9) and PTC (n = 8). RESULTS: Immunohistochemistry disclosed NOS2 and NOS3 immunoreactivity in PTC cells, the percentage of positive cells being greater than normal (P < 0.02). Real-time quantitative polymerase chain reaction (RTQ-PCR) showed that NOS2 and NOS3 mRNA levels were, respectively, increased (P < 0.02) by 2.6 +/- 0.6 and 4.2 +/- 1.1 times in PTC. RTQ-PCR demonstrated that VEGF, its receptors VEGFR-1 and VEGFR-2, and angiopoietin-2 and its receptor (Tie2) were also overexpressed (P < 0.05) in PTC. Correlations were found between ET-1 expression and that of NOS2, angiopoietin-1 and -2 (P < 0.05). NOS2 mRNA levels also correlated with those of NOS3 and angiopoietin-2 (P < 0.05). In thyroiditis, NOS2 immunoreactivity was observed in inflammatory cells whereas NOS2 mRNA levels were 12.1 +/- 1.6 times higher than normal (P < 0.005). CONCLUSIONS: This study revealed an activation of the NO pathway in thyroid carcinoma, which is interrelated to the ET-1 axis, both systems being overexpressed in concert with angiogenic factors. This global system might play a role in carcinogenesis and constitutes a potential target for anticancer therapy. |
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Authors:
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Julian E Donckier; Luc Michel; Monique Delos; Xavier Havaux; Ronald Van Beneden |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Clinical endocrinology Volume: 64 ISSN: 0300-0664 ISO Abbreviation: Clin. Endocrinol. (Oxf) Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-22 Completed Date: 2006-09-15 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0346653 Medline TA: Clin Endocrinol (Oxf) Country: England |
Other Details:
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Languages: eng Pagination: 703-10 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Surgery and Pathology, University Hospital of Mont-Godinne, Université Catholique de Louvain, Yvoir, Belgium. julian.donckier@mint.ucl.ac.be |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Angiopoietin-1 / analysis, genetics Angiopoietin-2 / analysis, genetics Carcinoma, Papillary / chemistry* Case-Control Studies Endothelin-1 / analysis* Female Hashimoto Disease / metabolism Humans Immunohistochemistry / methods Male Middle Aged Nitric Oxide Synthase / analysis*, genetics Nitric Oxide Synthase Type II / analysis, genetics Nitric Oxide Synthase Type III / analysis, genetics RNA, Messenger / analysis Receptor, TIE-2 / analysis, genetics Thyroid Neoplasms / chemistry* Vascular Endothelial Growth Factor A / analysis*, genetics Vascular Endothelial Growth Factor Receptor-1 / analysis, genetics Vascular Endothelial Growth Factor Receptor-2 / analysis, genetics |
| Chemical | |
Reg. No./Substance:
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0/Angiopoietin-1; 0/Angiopoietin-2; 0/Endothelin-1; 0/RNA, Messenger; 0/Vascular Endothelial Growth Factor A; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.10.1/Receptor, TIE-2; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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