{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:20:34Z","timestamp":1791220834063,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6118,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Swiss National Funds","award":["SNF 32-049494"],"award-info":[{"award-number":["SNF 32-049494"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Down\u2013regulation of KAI1 expression has been shown to be associated with formation of metastases or disease progression in prostate and pancreatic cancer. In the present study we analyzed the expression pattern of KAI1 in metastatic and nonmetastatic hepatocellular carcinomas (HCCs) in comparison with normal livers to evaluate whether alteration of KAI1 also facilitates the metastatic ability in this malignancy. Thirty\u2013nine primary HCCs and 10 normal liver tissue samples were studied for KAI1 messenger RNA (mRNA) expression with use of Northern blot analysis and <jats:italic toggle=\"yes\">in situ<\/jats:italic> hybridization. By Northern blot analysis, moderate to strong KAI1 mRNA expression was present in normal liver samples. In contrast, KAI1 mRNA expression in tissue samples of primary HCCs was markedly decreased compared with normal controls. The normal\/tumor ratio of KAI1 mRNA expression was 2.6:1 (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt; .01). Primary HCCs that gave rise to metastasis showed significantly lower KAI1 mRNA levels than nonmetastasized HCCs (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .05). As seen by <jats:italic toggle=\"yes\">in situ<\/jats:italic> hybridization, moderate to strong cytoplasmic KAI1 mRNA staining was present in almost all normal hepatocytes. Bile ducts, blood vessels, and connective tissue showed no or only faint KAI1 mRNA expression in the normal liver samples. In nonmetastatic HCCs, the cancer cells exhibited <jats:italic toggle=\"yes\">in situ<\/jats:italic> hybridization signals that were similar to the normal controls. In contrast, most of the primary HCC cells in samples with metastases showed only faint or moderate KAI1 mRNA expression predominantly in the perinuclear regions. When KAI1 mRNA expression of primary hepatocellular cancer cells was compared with metastasized cancer cells in lymph nodes, with intrahepatic satellite metastasis, or with peritoneal metastasis in the same patients, significantly lower (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .01) KAI1 mRNA levels were present in the metastasized HCC cells. Reduced KAI1 mRNA in HCC cells seems to influence their metastatic ability and thereby enhances the malignant potential of HCC<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510280606","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:33:46Z","timestamp":1090971226000},"page":"1481-1488","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":71,"title":["Kai1, A New Metastasis Suppressor Gene, Is Reduced in Metastatic Hepatocellular Carcinoma"],"prefix":"10.1097","volume":"28","author":[{"given":"Xiao-Zhong","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Friess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio F.","family":"Di 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