{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:07:45Z","timestamp":1782205665100,"version":"3.54.5"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Transforming growth factor \u03b21 (TGF\u03b21) signaling pathway is crucial for both human fibrogenesis and tumorigenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to investigate the usefulness of TGF\u03b21 and matrix metalloproteinase 2 (MMP2) as potential circulating markers for fibrotic valvular heart disease (FVHD) and invasiveness as well as of Fetuin A as a marker for calcification in patients with prolactinomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>The study population consisted of 147 subjects divided into four groups: 30 dopamine agonist (DA)-treated prolactinoma patients with proven FVHD and three control groups with normal echocardiograms: 43 DA-treated patients, 26 na\u00efve patients, and 48 healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed significantly higher serum TGF\u03b21 levels in all three patient groups than in the healthy subjects (21.4\u00b18.86 vs 19.1\u00b19.03 vs 20.7\u00b111.5 vs 15.8\u00b17.2\u200ang\/ml; <jats:italic>P<\/jats:italic>=0.032). Moreover, TGF\u03b21 levels were significantly higher in patients with macroprolactinomas and invasive prolactinomas than in those with microprolactinomas and noninvasive tumors respectively. In addition, a strong positive linear relationship between TGF\u03b21 levels and invasiveness score (<jats:italic>\u03c1<\/jats:italic>=0.924; <jats:italic>P<\/jats:italic>&lt;0.001) and a moderate correlation between TGF\u03b21 levels and tumor volume (<jats:italic>r<\/jats:italic>=0.546; <jats:italic>P<\/jats:italic>&lt;0.002) were observed in patients with invasive prolactinomas. By contrast, prolactin (PRL) levels exhibited a better correlation with tumor volume (<jats:italic>r<\/jats:italic>=0.721; <jats:italic>P<\/jats:italic>&lt;0.001) than with invasiveness score (<jats:italic>\u03c1<\/jats:italic>=0.436; <jats:italic>P<\/jats:italic>&lt;0.020). No significant difference was observed in Fetuin A levels between patients with FVHD and healthy controls. Results concerning MMP2 were unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TGF\u03b21, MMP2, and Fetuin A are not reliable biomarkers for valvular fibrosis and calcification in DA-treated patients with prolactinomas, but TGF\u03b21 may represent a useful serum marker for tumor invasiveness. The simultaneous determination of TGF\u03b21 and PRL levels could improve the noninvasive assessment of prolactinoma behavior.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-13-0081","type":"journal-article","created":{"date-parts":[[2013,6,26]],"date-time":"2013-06-26T03:14:02Z","timestamp":1372216442000},"page":"299-306","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":6,"title":["Transforming growth factor \u03b21 is not a reliable biomarker for valvular fibrosis but could be a potential serum marker for invasiveness of prolactinomas (pilot study)"],"prefix":"10.1093","volume":"169","author":[{"given":"Atanaska","family":"Elenkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliana","family":"Atanassova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgi","family":"Kirilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Vasilev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krassimir","family":"Kalinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Zacharieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"12","key":"1_17370940","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.4065\/77.12.1280","volume":"77","author":"Pritchett","year":"2002","journal-title":"Mayo Clinic Proceedings","ISSN":"https:\/\/id.crossref.org\/issn\/0025-6196","issn-type":"print"},{"key":"2_46238720","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1212\/01.WNL.0000083985.00343.F2","volume":"61","year":"2003","journal-title":"OGPL Neurology"},{"key":"3_46238721","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1212\/01.wnl.0000238508.68593.1d","volume":"67","year":"2006","journal-title":"OGPL Neurology"},{"issue":"1","key":"4_23452460","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1056\/NEJMoa054830","volume":"356","author":"Zanettini","year":"2007","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"23","key":"5_10574533","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1161\/01.CIR.102.23.2836","volume":"102","author":"Rothman","year":"2000","journal-title":"Circulation","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7322","issn-type":"print"},{"key":"6_42896045","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.pharmthera.2005.12.004","volume":"111","year":"2006","journal-title":"PHARMACOLOGY THERAPEUTICS"},{"issue":"1","key":"7_23452459","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1056\/NEJMoa062222","volume":"356","author":"Schade","year":"2007","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"12","key":"8_33422283","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1111\/j.1742-1241.2008.01779.x","volume":"62","author":"Bogazzi","year":"2008","journal-title":"International journal of clinical practice","ISSN":"https:\/\/id.crossref.org\/issn\/1368-5031","issn-type":"print"},{"issue":"1","key":"9_33486996","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1111\/j.1365-2265.2008.03458.x","volume":"70","author":"Herring","year":"2009","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"key":"10_46238722","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s11102-008-0134-2","volume":"12","year":"2009","journal-title":"Pituitary","ISSN":"https:\/\/id.crossref.org\/issn\/1386-341X","issn-type":"print"},{"issue":"3","key":"11_37472866","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/j.1365-2265.2010.03827.x","volume":"73","author":"Tan","year":"2010","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"issue":"4","key":"12_36382759","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1530\/EJE-09-0989","volume":"162","year":"2010","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"9","key":"13_31307171","doi-asserted-by":"publisher","first-page":"3348","DOI":"10.1210\/jc.2007-2658","volume":"93","year":"2008","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"1","key":"14_31006741","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1530\/EJE-08-0213","volume":"159","year":"2008","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"4","key":"15_31465256","doi-asserted-by":"publisher","first-page":"R11","DOI":"10.1530\/EJE-08-0365","volume":"159","year":"2008","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"1","key":"16_35041766","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/j.1365-2265.2009.03608.x","volume":"72","author":"Nachtigall","year":"2010","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"issue":"1","key":"17_42382682","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1530\/EJE-12-0121","volume":"167","year":"2012","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"10","key":"18_31646714","doi-asserted-by":"publisher","first-page":"3777","DOI":"10.1210\/jc.2007-1403","volume":"93","year":"2008","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"3","key":"19_18907749","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.ejphar.2005.03.010","volume":"513","author":"J\u00a0\u00a0hnichen","year":"2005","journal-title":"European journal of pharmacology","ISSN":"https:\/\/id.crossref.org\/issn\/0014-2999","issn-type":"print"},{"issue":"3","key":"20_32568249","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1002\/mds.22228","volume":"24","author":"Tan","year":"2009","journal-title":"Movement disorders : official journal of the Movement Disorder Society","ISSN":"https:\/\/id.crossref.org\/issn\/0885-3185","issn-type":"print"},{"key":"21_46238723","first-page":"44","volume":"15","year":"2011","journal-title":"Pituitary","ISSN":"https:\/\/id.crossref.org\/issn\/1386-341X","issn-type":"print"},{"issue":"6","key":"22_17678293","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","volume":"113","author":"Shi","year":"2003","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"issue":"2","key":"23_31618020","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","volume":"134","author":"Massague","year":"2008","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"issue":"10","key":"24_43709847","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/nrm3434","volume":"13","author":"Massague","year":"2012","journal-title":"Nature reviews. Molecular cell biology","ISSN":"https:\/\/id.crossref.org\/issn\/1471-0072","issn-type":"print"},{"issue":"9","key":"25_16493122","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1006\/jmcc.1996.0185","volume":"28","author":"Sigel","year":"1996","journal-title":"Journal of molecular and cellular cardiology","ISSN":"https:\/\/id.crossref.org\/issn\/0022-2828","issn-type":"print"},{"issue":"12","key":"26_36044314","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1161\/CIRCRESAHA.109.209809","volume":"105","author":"Souders","year":"2009","journal-title":"Circulation Research","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7330","issn-type":"print"},{"issue":"1","key":"27_22039019","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1365-2567.2006.02336.x","volume":"118","author":"Khan","year":"2006","journal-title":"Immunology","ISSN":"https:\/\/id.crossref.org\/issn\/0019-2805","issn-type":"print"},{"issue":"21","key":"28_11406422","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1161\/hc4601.099489","volume":"104","author":"Rabkin","year":"2001","journal-title":"Circulation","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7322","issn-type":"print"},{"issue":"24","key":"29_19561588","doi-asserted-by":"publisher","first-page":"22144","DOI":"10.1074\/jbc.M300744200","volume":"278","year":"2003","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"19","key":"30_28529567","doi-asserted-by":"publisher","first-page":"2533","DOI":"10.1161\/CIRCULATIONAHA.106.682450","volume":"115","year":"2007","journal-title":"Circulation","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7322","issn-type":"print"},{"issue":"5","key":"31_38528472","first-page":"636","volume":"19","author":"Cagli","year":"2010","journal-title":"The Journal of heart valve disease","ISSN":"https:\/\/id.crossref.org\/issn\/0966-8519","issn-type":"print"},{"key":"32_46238727","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.cyto.2012.11.011","volume":"61","year":"2013","journal-title":"Cytokine","ISSN":"https:\/\/id.crossref.org\/issn\/1043-4666","issn-type":"print"},{"key":"33_46238729","first-page":"61","volume":"1","year":"2006","journal-title":"Journal of neuro-oncology","ISSN":"https:\/\/id.crossref.org\/issn\/0167-594X","issn-type":"print"},{"issue":"1","key":"34_41080618","doi-asserted-by":"crossref","first-page":"53","DOI":"10.5301\/JBM.2011.8736","volume":"27","author":"Dave","year":"2012","journal-title":"The International journal of biological markers","ISSN":"https:\/\/id.crossref.org\/issn\/0393-6155","issn-type":"print"},{"issue":"4","key":"35_11483952","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1002\/ijc.1631","volume":"97","author":"Narai","year":"2002","journal-title":"International journal of cancer. Journal international du cancer","ISSN":"https:\/\/id.crossref.org\/issn\/0020-7136","issn-type":"print"},{"key":"36_36696225","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-4419-1664-8_7","volume":"668","author":"Lebrun","year":"2009","journal-title":"Advances in experimental medicine and biology","ISSN":"https:\/\/id.crossref.org\/issn\/0065-2598","issn-type":"print"},{"issue":"7","key":"37_19672555","doi-asserted-by":"publisher","first-page":"3837","DOI":"10.1073\/pnas.061358098","volume":"98","year":"2001","journal-title":"PNAS","ISSN":"https:\/\/id.crossref.org\/issn\/0027-8424","issn-type":"print"},{"issue":"2","key":"38_17732672","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2214\/ajr.181.2.1810577","volume":"181","author":"Sarlis","year":"2003","journal-title":"American Journal of Roentgenology","ISSN":"https:\/\/id.crossref.org\/issn\/0361-803X","issn-type":"print"},{"issue":"1","key":"39_23452436","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1056\/NEJMp068265","volume":"356","author":"Roth","year":"2007","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"6","key":"40_17360213","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/S0002-9440(10)64489-6","volume":"161","author":"Jian","year":"2002","journal-title":"American Journal Of Pathology","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9440","issn-type":"print"},{"issue":"2","key":"41_17820189","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1002\/jcp.10355","volume":"197","author":"Greene","year":"2003","journal-title":"Journal of cellular physiology","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9541","issn-type":"print"},{"issue":"1-2","key":"42_10487636","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1006\/mgme.2000.3059","volume":"71","author":"Moussad","year":"2000","journal-title":"Molecular genetics and metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/1096-7192","issn-type":"print"},{"issue":"1","key":"43_30633960","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.cardiores.2004.03.010","volume":"63","year":"2004","journal-title":"Cardiovascular Research","ISSN":"https:\/\/id.crossref.org\/issn\/0008-6363","issn-type":"print"},{"issue":"6","key":"44_40967285","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1510\/icvts.2010.244384","volume":"11","year":"2010","journal-title":"Interactive CardioVascular and Thoracic Surgery","ISSN":"https:\/\/id.crossref.org\/issn\/1569-9293","issn-type":"print"},{"issue":"1","key":"45_16082766","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/nm0195-74","volume":"1","author":"Grainger","year":"1995","journal-title":"Nature medicine","ISSN":"https:\/\/id.crossref.org\/issn\/1078-8956","issn-type":"print"},{"issue":"3-4","key":"46_16858697","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/00019501-199703000-00004","volume":"8","author":"Tashiro","year":"1997","journal-title":"Coronary artery disease","ISSN":"https:\/\/id.crossref.org\/issn\/0954-6928","issn-type":"print"},{"key":"47_46238733","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1465-9921-13-116","volume":"13","year":"2012","journal-title":"Respiratory research","ISSN":"https:\/\/id.crossref.org\/issn\/1465-9921","issn-type":"print"},{"key":"49_46238734","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/S1081-1206(10)61516-5","volume":"91","year":"2003","journal-title":"ANNALS OF ALLERGY ASTHMA IMMUNOLOGY"},{"key":"50_46238735","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s11033-012-2100-3","volume":"40","year":"2013","journal-title":"Molecular biology reports","ISSN":"https:\/\/id.crossref.org\/issn\/0301-4851","issn-type":"print"},{"issue":"10","key":"51_19408833","doi-asserted-by":"publisher","first-page":"4179","DOI":"10.1210\/en.2005-0430","volume":"146","year":"2005","journal-title":"Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0013-7227","issn-type":"print"},{"issue":"5","key":"52_10826430","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1046\/j.1365-2826.1999.00336.x","volume":"11","author":"Coya","year":"1999","journal-title":"Journal of neuroendocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0953-8194","issn-type":"print"},{"issue":"4","key":"53_44260068","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1177\/147323001204000407","volume":"40","author":"Jiang","year":"2012","journal-title":"Journal of International Medical Research","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0605","issn-type":"print"},{"issue":"2","key":"54_43244796","doi-asserted-by":"publisher","first-page":"R69","DOI":"10.1530\/JME-12-0113","volume":"49","year":"2012","journal-title":"Journal of Molecular Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0952-5041","issn-type":"print"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/169\/3\/299.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/169\/3\/299.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:29:14Z","timestamp":1676392154000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/169\/3\/299\/6661671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9]]},"references-count":53,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/eje-13-0081","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9]]}}}