{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:24:11Z","timestamp":1765545851769},"reference-count":43,"publisher":"Wiley","issue":"S4","license":[{"start":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T00:00:00Z","timestamp":1384819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Colorectal cancer is the third leading cause of cancer death in <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>apan and the <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>nited <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>tates and is strongly associated with obesity, especially visceral obesity. Several metabolic mediators, such as adiponectin, have been suspected to play a role in obesity\u2010related carcinogenesis. In a previous human study, the existence of a significant correlation between the number of human dysplastic aberrant crypt foci (<jats:styled-content style=\"fixed-case\">ACF<\/jats:styled-content>) and the visceral fat area was demonstrated, and also that of a significant inverse correlation between the number of dysplastic <jats:styled-content style=\"fixed-case\">ACF<\/jats:styled-content> and the plasma adiponectin level. Other studies have investigated the effect of adiponectin under the normal and high\u2010fat diet conditions in a mouse model of azoxymethane\u2010induced colon cancer. Enhanced formation of both <jats:styled-content style=\"fixed-case\">ACF<\/jats:styled-content> and tumors was observed in the adiponectin\u2010deficient mice, as compared with that in the wild\u2010type, under the high\u2010fat diet condition but not under the normal diet condition. Furthermore, that the 5\u2032\u2010<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010activated kinase\/mammalian target of rapamycin pathway is involved in the promotion of colorectal carcinogenesis in adiponectin\u2010deficient mice under the high\u2010fat diet condition was shown. Therefore, that the 5\u2032\u2010<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010activated kinase\/mammalian target of rapamycin signaling pathway may play an important role in colorectal carcinogenesis was speculated. Metformin, a biguanide derivative widely used in the treatment of diabetes mellitus, has been shown to exert a suppressive effect on <jats:styled-content style=\"fixed-case\">ACF<\/jats:styled-content> formation in both mouse models and humans. Therefore, metformin might be a promising candidate as a safe drug for chemoprevention of colorectal carcinogenesis. Further studies with high evidence levels, such as randomized, controlled studies, are needed to clarify these relationships.<\/jats:p>","DOI":"10.1111\/jgh.12240","type":"journal-article","created":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T05:21:47Z","timestamp":1384924907000},"page":"41-47","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Colon epithelial proliferation and carcinogenesis in diet\u2010induced obesity"],"prefix":"10.1111","volume":"28","author":[{"given":"Hirokazu","family":"Takahashi","sequence":"first","affiliation":[{"name":"Gastroenterology Division Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Hosono","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Endo","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.48.1562"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1158\/1055-9965.133.14.1","article-title":"Diabetes mellitus and subsite\u2010specific colorectal cancer risks in the Iowa Women's Health Study","volume":"14","author":"Limburg PJ","year":"2005","journal-title":"Cancer Epidemiol. 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