{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:16Z","timestamp":1787013976404,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T00:00:00Z","timestamp":1386115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:p>\n                    The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a\n                    <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content>\n                    assay and the mean IC\n                    <jats:sub>50<\/jats:sub>\n                    values determined to be 1.6\u00a0\u00b1\u00a01.2 (range, 0.6\u20134.0) and 1.2\u00a0\u00b1\u00a01.1 (range, 0.4\u20133.4)\u00a0nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean\n                    <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>\n                    <jats:sub>50<\/jats:sub>\n                    value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9\u00a0\u00b1\u00a04.7\u00a0nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2\u00a0weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    were detected and apoptotic cells were observed. When the expressions of cell\u2010cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low\u2010\n                    <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>\n                    <jats:sub>50<\/jats:sub>\n                    group compared with the high\u2010\n                    <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>\n                    <jats:sub>50<\/jats:sub>\n                    group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction.\n                  <\/jats:p>","DOI":"10.1111\/cas.12317","type":"journal-article","created":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T04:38:41Z","timestamp":1383280721000},"page":"110-116","source":"Crossref","is-referenced-by-count":51,"title":["High antitumor activity of pladienolide B and its derivative in gastric cancer"],"prefix":"10.1111","volume":"105","author":[{"given":"Momoko","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Muguruma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadahiko","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutaka","family":"Sannomiya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Goji","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Okahisa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Mikasa","sequence":"additional","affiliation":[{"name":"Medical Education Sapport Center Faculty of Medicine Tokushima University Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Oe Kyodo Hospital Yoshinogawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Iwata","sequence":"additional","affiliation":[{"name":"Tsukuba Research Laboratories Eisai Co., Ltd Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Institutes of Health Biosciences University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i11.1262"},{"key":"e_1_2_7_4_1","unstructured":"Cancer Statistics zrin Japan\u20102012. 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