{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:22:49Z","timestamp":1740104569373,"version":"3.37.3"},"reference-count":63,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T00:00:00Z","timestamp":1497225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","award":["#3395"],"award-info":[{"award-number":["#3395"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression <jats:italic>per se<\/jats:italic> on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1\u2010deficient HCT116 cell line and its MLH1\u2010complemented isogenic clone, mlh1\u20103, were implanted onto the caecum of NOD\/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116\u2010derived tumors were more voluminous compared to the mlh1\u20103 ones (<jats:italic>P =<\/jats:italic> .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (<jats:italic>P =<\/jats:italic> .007 and <jats:italic>P =<\/jats:italic> .035, respectively). Mlh1\u20103\u2010grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1\u20103 group (<jats:italic>P =<\/jats:italic> .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1\u2010deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such.<\/jats:p>","DOI":"10.1002\/gcc.22472","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T01:42:41Z","timestamp":1494985361000},"page":"681-690","source":"Crossref","is-referenced-by-count":2,"title":["Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer"],"prefix":"10.1002","volume":"56","author":[{"given":"Katy","family":"Meunier","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Univ Paris 06, INSERM, CNRS, Centre de Recherche Saint\u2010Antoine (CRSA) Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Ferron","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, 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Paris, H\u00f4pital Lariboisi\u00e8re Paris France"},{"name":"Paris Diderot University, USPC, Sorbonne Paris Cit\u00e9 Paris France"},{"name":"INSERM UMR 965, Angiogenesis and Translational Research Department H\u00f4pital Lariboisi\u00e8re Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5353-8889","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Praz","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Univ Paris 06, INSERM, CNRS, Centre de Recherche Saint\u2010Antoine (CRSA) Paris 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