{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:53:18Z","timestamp":1787014398307,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T00:00:00Z","timestamp":1143504000000},"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":["Int J Experimental Path"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Mlh1<\/jats:italic>\n                    \u2010knockout mice have been developed as a useful model of hereditary non\u2010polyposis colorectal cancer (HNPCC). In this study, we analyzed the pathology of gastrointestinal tumours (GIT) in these mice in detail and examined the possible effects of ionizing radiation on the induction of intestinal tumours to evaluate the late response to radiotherapy in HNPCC.\n                    <jats:italic>Mlh1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2013<\/jats:italic>\n                      \/\n                      <jats:italic>\u2013<\/jats:italic>\n                    <\/jats:sup>\n                    mice spontaneously developed GIT and thymic lymphomas by 48 weeks. GIT included not only well differentiated adenocarcinomas but also poorly differentiated and mucinous adenocarcinomas, suggesting that this mouse is a good model for HNPCC. In contrast to colon cancers from HNPCC patients, however, carcinomas of\n                    <jats:italic>Mlh1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice expressed p53 and showed a lack of transforming growth factor (\n                    <jats:italic>TGF<\/jats:italic>\n                    )\n                    <jats:italic>\u2010\u03b2RII<\/jats:italic>\n                    mutation, which resulted in the expression of TGF\u2010\u03b2RII protein. Irradiation of 10\u2010week\u2010old\n                    <jats:italic>Mlh1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice accelerated GIT development but had little effect at 2 weeks.\n                    <jats:italic>Mlh1<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    and\n                    <jats:italic>Mlh1<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice were not susceptible to spontaneous or radiation\u2010induced thymic lymphomas and GIT until 72 weeks after birth. The development and pathology of GIT in\n                    <jats:italic>Mlh1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice suggest that this mouse is a good model for HNPCC, although tumour\u2010related responsible genes might be different from HNPCC. As X\u2010ray exposure promoted carcinogenesis of GIT in adult\n                    <jats:italic>Mlh1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice, an increased risk of secondary cancers after radiotherapy for HNPCC patients should be taken into consideration.\n                  <\/jats:p>","DOI":"10.1111\/j.0959-9673.2006.00464.x","type":"journal-article","created":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T10:02:08Z","timestamp":1143540128000},"page":"89-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Accelerated growth of intestinal tumours after radiation exposure in Mlh1\u2010knockout mice: evaluation of the late effect of radiation on a mouse model of HNPCC"],"prefix":"10.1111","volume":"87","author":[{"given":"Yutaka","family":"Tokairin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuko","family":"Kakinuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieko","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisaku","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Akashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Miki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuyuki","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehisa","family":"Iwai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,3,28]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"3087","article-title":"Loss 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