{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:34:41Z","timestamp":1789695281449,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST105\u20102320\u2010B\u2010038\u2010022\u2010MY3"],"award-info":[{"award-number":["MOST105\u20102320\u2010B\u2010038\u2010022\u2010MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST105\u20102628\u2010B\u2010038\u2010001\u2010MY4"],"award-info":[{"award-number":["MOST105\u20102628\u2010B\u2010038\u2010001\u2010MY4"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["12310\u2010022"],"award-info":[{"award-number":["12310\u2010022"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The phthalate plasticizer, di(2\u2010ethyl\u2010hexyl) phthalate (DEHP), and its derived metabolites are common anthropogenic environmental toxins, which are known to act as endocrine disruptors. Numerous studies have associated DEHP with disruption of sex hormones, abnormal development of reproductive organs, allergies, and inflammation. Its role in promoting inflammation has been reported by both human epidemiological and animal studies. In stomach tissue, chronic inflammation is known to accompany mucosal damage, and pave the way to gastritis, stomach ulcers, and ultimately gastric cancer. Eastern Asian populations possess the highest gastric cancer incidences in the world. Coincidentally, East Asia is one of the world's major sites for plastics manufacture and export. Thus, possible correlations between DEHP, a common plasticizer, and gastric cancer are of great interest. Our study revealed several critical findings. First, even at very low dosage, mimicking the residual plasticizer exposure, detrimental effects of DEHP on gastric cells can be detected. Second, gastric cells treated with DEHP increased cyclooxygenase\u20102 (COX\u20102) in a time\u2010dependent manner. Third, promoter deletion studies revealed a critical role of nuclear factor\u2010kappa B (NF\u2010\u03baB) for\n                    <jats:italic>COX\u20102<\/jats:italic>\n                    gene responses. Finally, our results indicated that a low concentration of DEHP is able to trigger COX\u20102 activation via the extracellular signal\u2013regulated kinase (ERK1\/2) and NF\u2010\u03baB signaling pathway. Taken together, we demonstrate that very low doses of DEHP enhance the expression of the prototypical inflammatory gene,\n                    <jats:italic>COX\u20102<\/jats:italic>\n                    , in gastric cancer cells via ERK1\/2 and NF\u2010\u03baB activation. This study provides important insights into the inflammatory process and damages associated with phthalate plasticizers exposure.\n                  <\/jats:p>","DOI":"10.1002\/tox.22820","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T02:40:32Z","timestamp":1563331232000},"page":"1191-1198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Phthalate plasticizer di(2\u2010ethyl\u2010hexyl) phthalate induces cyclooxygenase\u20102 expression in gastric adenocarcinoma cells"],"prefix":"10.1002","volume":"34","author":[{"given":"Jhen\u2010Hong","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy School of Pharmacy, Taipei Medical University  Taipei Taiwan"},{"name":"Department of Medical Genetics College of Medicine, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Shiuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy School of Pharmacy, Taipei Medical University  Taipei Taiwan"},{"name":"PhD Program in Clinical Drug Development of Chinese Herbal Medicine College of Pharmacy, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy School of Pharmacy, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo\u2010Hao","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy School of Pharmacy, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che\u2010Mai","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy School of Pharmacy, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ku\u2010Chung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology School of Medicine, College of Medicine, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0793-8769","authenticated-orcid":false,"given":"Yi\u2010Fan","family":"Chen","sequence":"additional","affiliation":[{"name":"Master Program for Clinical Pharmacogenomics and Pharmacoproteomics Taipei Medical University  Taipei Taiwan"},{"name":"The PhD Program for Translational Medicine College of Medical Science and Technology, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Chiao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy School of Pharmacy, Taipei Medical University  Taipei Taiwan"},{"name":"Master Program for Clinical Pharmacogenomics and Pharmacoproteomics Taipei Medical University  Taipei Taiwan"},{"name":"Department of Pharmacy; Integrative Research Center in Critical Care Wan Fang Hospital, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197211302872203"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/238411a0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.170.3956.460"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.413194"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600610107"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.8245129"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/074823378700300208"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.824565"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-53-14167"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.95103582"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.97105802"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.89.2.188"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.00108895"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/58.2.350"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/58.2.339"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.01109229"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(01)00419-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.03.010"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.7187"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.11474"},{"key":"e_1_2_7_22_1","first-page":"1941s","article-title":"Phenotypic and genotypic events in gastric carcinogenesis","volume":"54","author":"Correa P","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-011-0041-5"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027452"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21847"},{"key":"e_1_2_7_27_1","unstructured":"US Environmental Protection Agency. 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