{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:35:55Z","timestamp":1792787755420,"version":"4.5.0"},"reference-count":59,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University","award":["RA66\/021"],"award-info":[{"award-number":["RA66\/021"]}],"id":[{"id":"https:\/\/ror.org\/028wp3y58","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Integr Cancer Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, particularly in patients with cirrhosis. Genistein (GEN), a tyrosine kinase inhibitor with a favorable safety profile, has potential as a chemoprotective agent in high-risk populations. This study evaluated the effects of GEN in a rat model of diethylnitrosamine (DEN)-induced cirrhosis and HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-three male Sprague Dawley rats were randomized into three groups (n=11\/group): Control, HCC, and HCC+GEN. HCC was induced by weekly intraperitoneal DEN injections (70 mg\/kg) for 16 weeks. From weeks 8\u201316, the GEN group received oral genistein (50 mg\/kg\/day), while other groups received vehicle. Liver tissues were examined histopathologically and immunohistochemically for HCC, caspase-9, ERK-1, \u03b1-SMA, and MMP-2. Tumor burden was calculated to reflect tumor size and number. Serum AFP, p53, and biochemical parameters were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tumor burden was significantly increased in the HCC group compared with controls and was significantly reduced by GEN treatment (p=0.002). Elevated serum AFP and p53 levels in the HCC group were significantly decreased with GEN. Although cirrhosis developed in both HCC groups, collagen deposition was significantly lower in the GEN-treated rats. GEN treatment was associated with reduced expression of ERK-1, \u03b1-SMA, and MMP-2, and increased caspase-9 expression, indicating anti-proliferative, anti-fibrotic, and pro-apoptotic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genistein reduced tumor burden, serum tumor markers, and liver fibrosis in a rat model of HCC, supporting its potential as a chemoprotective agent in cirrhotic livers. Further dose-optimization and clinical studies are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15347354261492310","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:11:26Z","timestamp":1790082686000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The Protective and Anti-fibrotic Properties of Genistein in a Rat Model of Cirrhosis and Liver Cancer"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1649-5373","authenticated-orcid":false,"given":"Maneerat","family":"Chayanupatkul","sequence":"first","affiliation":[{"name":"Chulalongkorn University, Bangkok, Thailand"},{"name":"Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanjana","family":"Somanawat","sequence":"additional","affiliation":[{"name":"Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natcha","family":"Wanpiyarat","sequence":"additional","affiliation":[{"name":"Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duangporn","family":"Werawatganon","sequence":"additional","affiliation":[{"name":"Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.4823955"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.2217\/hep-2020-0012"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.019"},{"issue":"2","key":"e_1_3_6_6_2","first-page":"135","article-title":"Biological properties of genistein. A review of in vitro and in vivo data","volume":"57","author":"Polkowski K","year":"2000","unstructured":"Polkowski K, Mazurek AP. Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol Pharm. 2000;57(2):135-155.","journal-title":"Acta Pol Pharm"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-020-02962-z"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2005.05.021"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-960171"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","unstructured":"Dhanasekaran R Bandoh S Roberts LR. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances. F1000Res. 2016;5:F1000 Faculty Rev-879. doi:10.12688\/f1000research.6946.1.","DOI":"10.12688\/f1000research.6946.1"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2537"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900662"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/0023677215570086"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194981"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.52586\/5050"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)31952-0"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.11.027"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2012.0141"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.4103\/ijpvm.IJPVM_249_16"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-5222-8"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.4952"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.323"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2022.2031515"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100353"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20538"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15593"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.S488927"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415587978"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/app10020447"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.18006\/2023.11(5).822.833"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2008.04.010"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i8.1175"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.24506"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.S460922"},{"issue":"4","key":"e_1_3_6_35_2","first-page":"237","article-title":"Clinical associations and prognostic significance of serum anti-p53 antibodies in Thai patients with hepatocellular carcinoma","volume":"18","author":"Tangkijvanich P","year":"2000","unstructured":"Tangkijvanich P, Janchai A, Charuruks N, et al. Clinical associations and prognostic significance of serum anti-p53 antibodies in Thai patients with hepatocellular carcinoma. Asian Pac J Allergy Immunol. 2000;18(4):237-243.","journal-title":"Asian Pac J Allergy Immunol"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i24.3559"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099255"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.451"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1515\/cclm.2006.091"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5411.156"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2018.4369"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1367364"},{"issue":"4","key":"e_1_3_6_43_2","first-page":"1093","article-title":"beta-catenin siRNA regulation of apoptosis- and angiogenesis-related gene expression in hepatocellular carcinoma cells: potential uses for gene therapy","volume":"24","author":"Wang XH","year":"2010","unstructured":"Wang XH, Sun X, Meng XW, et al. beta-catenin siRNA regulation of apoptosis- and angiogenesis-related gene expression in hepatocellular carcinoma cells: potential uses for gene therapy. Oncol Rep. 2010;24(4):1093-1099.","journal-title":"Oncol Rep"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13123026"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8454"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.8027"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-14-26"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1023002216413"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280111"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/5338212"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2019.07.007"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-010-9770-2"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2022.0449"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2021.105961"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/bf01308606"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v8.i4.739"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/36381"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114472"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i12.1753"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.09.014"}],"container-title":["Integrative Cancer Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15347354261492310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15347354261492310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15347354261492310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:19:05Z","timestamp":1790389145000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15347354261492310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":59,"alternative-id":["10.1177\/15347354261492310"],"URL":"https:\/\/doi.org\/10.1177\/15347354261492310","relation":{},"ISSN":["1534-7354","1552-695X"],"issn-type":[{"value":"1534-7354","type":"print"},{"value":"1552-695X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"article-number":"15347354261492310"}}