{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:26:52Z","timestamp":1767166012184,"version":"build-2238731810"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,5,25]],"date-time":"2013-05-25T00:00:00Z","timestamp":1369440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:p>\n                    The incidence of colorectal cancer has been increasing and is associated with obesity and diabetes. We have found that type 2 diabetes model KK\u2010\n                    <jats:italic>A<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>y<\/jats:italic>\n                    <\/jats:sup>\n                    \/TaJcl (KK\u2010\n                    <jats:italic>A<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>y<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice develop tumors within a short period after treatment with azoxymethane (AOM). However, factors that contribute to the promotion of carcinogenesis have not been clarified. Therefore, we looked at the genetic background of\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    , including two genetic characteristics of\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    \/TaJcl (\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    ) mice and C57BL\/6J\u2010Ham\u2010\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    \/+ (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    ) mice, compared with other non\u2010obese and non\u2010diabetic mouse strains C57BL\/6J and\n                    <jats:styled-content style=\"fixed-case\">ICR<\/jats:styled-content>\n                    , and induced colorectal premalignant lesions, aberrant crypt foci (\n                    <jats:styled-content style=\"fixed-case\">ACF<\/jats:styled-content>\n                    ), and tumors using AOM (150\u00a0\u03bcg\/mouse\/week for 4\u00a0weeks and 200\u00a0\u03bcg\/mouse\/week for 6\u00a0weeks, respectively). The mice with a diabetes feature,\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    , developed significantly more\n                    <jats:styled-content style=\"fixed-case\">ACF<\/jats:styled-content>\n                    , 67 and 61 per mouse, respectively, whereas\n                    <jats:styled-content style=\"fixed-case\">ICR<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    , and C57BL\/6J mice developed 42, 24, and 18\n                    <jats:styled-content style=\"fixed-case\">ACF<\/jats:styled-content>\n                    \/mouse, respectively, at 17\u00a0weeks of age. Serum insulin and triglyceride levels in\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    <jats:italic>\u2010<\/jats:italic>\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    mice were quite high compared with other non\u2010diabetic mouse strains. Interestingly,\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    mice developed more colorectal tumors (2.7\u00a0\u00b1\u00a02.3 tumor\/mouse) than\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    mice (1.2\u00a0\u00b1\u00a01.1 tumor\/mouse) at 25\u00a0weeks of age, in spite of similar diabetic conditions. The colon cancers that developed in both\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    mice showed similar activation of \u03b2\u2010catenin signaling. However,\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    levels of inflammatory factors related to the activation of macrophages were significantly higher in colorectal cancer of\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>\n                        A\n                        <jats:sup>y<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:styled-content>\n                    mice than in\n                    <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\n                    . These data indicate that factors such as insulin resistance and dyslipidemia observed in obese and diabetic patients could be involved in susceptibility to colorectal carcinogenesis. In addition, increase of tumor\u2010associated macrophages may play important roles in the stages of promotion of colorectal cancer.\n                  <\/jats:p>","DOI":"10.1111\/cas.12162","type":"journal-article","created":{"date-parts":[[2013,4,2]],"date-time":"2013-04-02T02:35:08Z","timestamp":1364870108000},"page":"835-843","source":"Crossref","is-referenced-by-count":9,"title":["<scp>\n                      <i>\n                        A\n                        <sup>y<\/sup>\n                      <\/i>\n                    <\/scp>\n                    allele promotes azoxymethane\u2010induced colorectal carcinogenesis by macrophage migration in hyperlipidemic\/diabetic\n                    <scp>KK<\/scp>\n                    mice"],"prefix":"10.1111","volume":"104","author":[{"given":"Kumiko","family":"Ito","sequence":"first","affiliation":[{"name":"Division of Cancer Prevention Research National Cancer Center Research Institute Tokyo Japan"},{"name":"School of Life Sciences, 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