{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:32:12Z","timestamp":1784658732324,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,4,18]],"date-time":"2011-04-18T00:00:00Z","timestamp":1303084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peritoneal dissemination including omental metastasis is the most frequent route of metastasis and an important prognostic factor in advanced ovarian cancer. We analyzed the publicly available microarray dataset (GSE2109) using binary regression and found that the transforming growth factor (TGF)\u2010beta signaling pathway was activated in omental metastases as compared to primary sites of disease. Immunohistochemical analysis of TGF\u2010beta receptor type 2 and phosphorylated SMAD2 indicated that both were upregulated in omental metastases as compared to primary disease sites. Treatment of the mouse ovarian cancer cell line HM\u20101 with recombinant TGF\u2010\u03b21 promoted invasiveness, cell motility and cell attachment while these were suppressed by treatment with A\u201083\u201001, an inhibitor of the TGF\u2010\u03b2 signaling pathway. Microarray analysis of HM\u20101 cells treated with TGF\u2010\u03b21 and\/or A\u201083\u201001 revealed that A\u201083\u201001 efficiently inhibited transcriptional changes that are induced by TGF\u2010\u03b21. Using gene set enrichment analysis, we found that genes upregulated by TGF\u2010\u03b21 in HM\u20101 cells were also significantly upregulated in omental metastases compared to primary sites in the human ovarian cancer dataset, GSE2109 (false discovery rate (FDR) <jats:italic>q<\/jats:italic> = 0.086). Therapeutic effects of A\u201083\u201001 in a mouse model of peritoneal dissemination were examined. Intraperitoneal injection of A\u201083\u201001 (150 \u03bcg given three times weekly) significantly improved survival (<jats:italic>p<\/jats:italic> = 0.015). In summary, these results show that the activated TGF\u2010\u03b2 signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer.<\/jats:p>","DOI":"10.1002\/ijc.25961","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T15:05:48Z","timestamp":1296745548000},"page":"20-28","source":"Crossref","is-referenced-by-count":69,"title":["The activated transforming growth factor\u2010beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer"],"prefix":"10.1002","volume":"130","author":[{"given":"Shogo","family":"Yamamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriomi","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Mandai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Oura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsukasa","family":"Baba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzo","family":"Hamanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Sook","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Abiko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Konishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,18]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"609","article-title":"Ovarian cancer: an overview","volume":"80","author":"Roett MA","year":"2009","journal-title":"Am Fam Physician"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(06)70939-1"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-117"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.316"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/oli.2006.0053"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.256"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e31819d90c8"},{"key":"e_1_2_6_9_2","unstructured":"R Development Core Team. 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