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ID 106055
タイトル別表記
プラジェノライドB及びその誘導体は胃癌に対して高い抗腫瘍活性を有する
Pladienolide is active on gastric cancer
著者
佐藤, 桃子 徳島大学大学院医科学教育部(医学専攻)
矢野, 弘美 University of Tokushima
Sannnomiya, Katsutaka University of Tokushima
Wada, Satoshi Oe Kyodo Hospital
Iwata, Masao Eisai Co., Ltd
キーワード
Apoptosis
ascites
gastric cancer
pladienolide B
RNA splicing
資料タイプ
学位論文
抄録
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 MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6–4.0) and 1.2 ± 1.1 (range, 0.4–3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, 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 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle 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-IC50 group compared with the high-IC50 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.
掲載誌名
Cancer Science
ISSN
13497006
cat書誌ID
AA12100165
出版者
Wiley|Japanese Cancer Association
105
1
開始ページ
110
終了ページ
116
発行日
2013-11-01
備考
内容要旨・審査要旨・論文本文の公開
内容要旨・審査要旨 : LID201403051005.pdf
論文本文 : LID201405271003.pdf
本論文は, 著者Momoko Satoの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.( https://creativecommons.org/licenses/by-nc/3.0/ )
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2660号
学位記番号
甲医第1186号
学位授与年月日
2014-01-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院