{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:16:43Z","timestamp":1783325803751,"version":"3.54.6"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Record Open"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>On gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd\u2010EOB\u2010DTPA) magnetic resonance imaging, canine hepatocellular carcinoma (HCC) and hepatocellular adenoma (HCA) typically exhibit low and high signal intensities in the hepatobiliary phase, respectively. Reduced transporter protein expression is associated with decreased Gd\u2010EOB\u2010DTPA uptake. However, the specific transporters involved in Gd\u2010EOB\u2010DTPA uptake in canine HCC remain unknown. This exploratory study aimed to assess the mRNA expression of transporters that are downregulated in canine HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      For the bioinformatics analysis, an RNA sequencing dataset comprising 14 canine HCC samples and four normal liver samples was obtained from the DDBJ BioProject repository. Differentially expressed genes (DEGs) were evaluated for members of the organic anion transporting polypeptides (OATP1\u20106) family, multidrug resistance\u2010associated protein 2 (MRP2), bile salt export pump (BSEP), breast cancer resistance protein (BCRP), organic cation transporter 1 (OCT1) and multidrug resistance\u2010associated protein 3 (MRP3) in comparison between HCC and normal liver tissues. Genes with an absolute log\u2010fold change greater than 1 and a nominal\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value less than 0.05 were considered candidate DEGs. For clinical samples, surgically resected samples from eight canine HCCs and four canine HCAs were evaluated. RNA was extracted from the samples, and the expression levels of OATP1A2 were compared between HCCs and HCAs using real\u2010time quantitative polymerase chain reaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In bioinformatics analysis, upregulated DEGs in HCC included OATP3A1\/\n                      <jats:italic>SLCO3A1<\/jats:italic>\n                      and OATP5A1\/\n                      <jats:italic>SLCO5A1<\/jats:italic>\n                      , whereas downregulated DEGs included OATP1A2\/\n                      <jats:italic>SLCO1A2<\/jats:italic>\n                      . In clinical samples, OATP1A2 mRNA expression was significantly lower in HCC than in HCA (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Downregulation of OATP1A2 is associated with canine HCC and may contribute to reduced Gd\u2010EOB\u2010DTPA uptake.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/vro2.70038","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:37:28Z","timestamp":1783323448000},"source":"Crossref","is-referenced-by-count":0,"title":["OATP1A2 mRNA downregulation in canine hepatocellular carcinoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Shohei","family":"Kurokawa","sequence":"first","affiliation":[{"name":"Senri Momoyamadai Animal Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Motegi","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Molecular Pathophysiology Treatment Cooperative Department of Veterinary Medicine Faculty of Agriculture Tokyo University of Agriculture and Technology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Akiyoshi","sequence":"additional","affiliation":[{"name":"Neovets Veterinary Referral Center  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-913X","authenticated-orcid":false,"given":"Toshiyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Advanced Diagnosis and Treatment School of Veterinary Science Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/vetr.1083","article-title":"Comparing the CT and MRI findings for canine primary hepatocellular lesions","volume":"190","author":"Kurokawa S","year":"2022","journal-title":"Vet Rec"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1136\/vetreco-2019-000371","article-title":"Assessment of hepatitis and fibrosis using Gd\u2010EOB\u2010DTPA MRI in dogs","volume":"7","author":"Tanaka T","year":"2020","journal-title":"Vet Rec Open"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/vru.12419","article-title":"Gadoxetate disodium (GD\u2010EOB\u2010DTPA) contrast enhanced magnetic resonance imaging characteristics of hepatocellular carcinoma in dogs","volume":"57","author":"Constant C","year":"2016","journal-title":"Vet Radiol Ultrasound"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1124\/dmd.123.001492","article-title":"Association between gadoxetic acid\u2010enhanced magnetic resonance imaging, organic anion transporters, and farnesoid X receptor in benign focal liver lesions","volume":"52","author":"Rosmalen BV","year":"2024","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1007\/s00330-011-2165-8","article-title":"The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging","volume":"21","author":"Kitao A","year":"2011","journal-title":"Eur Radiol"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.4161\/cbt.11.9.15176","article-title":"The analysis of organic anion transporting polypeptide (OATP) mRNA and protein patterns in primary and metastatic liver cancer","volume":"11","author":"Wlcek K","year":"2011","journal-title":"Cancer Biol Ther"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1124\/dmd.114.061580","article-title":"Interspecies variability in expression of hepatobiliary transporters across human, dog, monkey, and rat as determined by quantitative proteomics","volume":"43","author":"Wang L","year":"2015","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1186\/s12917-025-05103-1","article-title":"PRC1, CDCA3, and CDC20 are upregulated and Treg numbers are decreased in canine massive hepatocellular carcinoma","volume":"21","author":"Tanaka T","year":"2025","journal-title":"BMC Vet Res"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1124\/dmd.111.041814","article-title":"Hepatic uptake in the dog: comparison of uptake in hepatocytes and human embryonic kidney cells expressing dog organic anion\u2010transporting polypeptide 1B4","volume":"39","author":"Wilby AJ","year":"2011","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.7150\/jca.17778","article-title":"Diagnostic value of Gd\u2010EOB\u2010DTPA\u2010MRI for hepatocellular adenoma: a meta\u2010analysis","volume":"8","author":"Guo Y","year":"2017","journal-title":"J Cancer"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"E32","DOI":"10.1111\/hepr.12453","article-title":"Preserved or enhanced OATP1B3 expression in hepatocellular adenoma subtypes with nuclear accumulation of \u03b2\u2010catenin","volume":"45","author":"Fukusato T","year":"2015","journal-title":"Hepatol Res"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1007\/s00330-020-07434-z","article-title":"Hepatospecific MR contrast agent uptake on hepatobiliary phase can be used as a biomarker of marked \u03b2\u2010catenin activation in hepatocellular adenoma","volume":"31","author":"Reizine E","year":"2021","journal-title":"Eur Radiol"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1477-2574.2010.00222.x","article-title":"Malignant transformation of hepatocellular adenomas into hepatocellular carcinomas: a systematic review including more than 1600 adenoma cases","volume":"12","author":"Stoot JHMB","year":"2010","journal-title":"HPB (Oxford)"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1186\/s12917-019-2038-y","article-title":"Magnetic resonance imaging of liver tumors using gadoxetic acid (Gd\u2010EOB\u2010DTPA)\u2014pilot study","volume":"15","author":"Borusewicz P","year":"2019","journal-title":"BMC Vet Res"}],"container-title":["Veterinary Record 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