アクセス数 : ?
ダウンロード数 : ?
ID 115599
著者
Lila, Amr S. Abu Tokushima University|Zagazig University|Hail University
Fukushima, Masakazu Tokushima University
Huang, Cheng-Long Kyoto University
Wada, Hiromi Kyoto University
キーワード
malignant pleural mesothelioma
PEG-coated shRNA-lipoplex
pemetrexed
short hairpin RNA
thymidylate synthase
資料タイプ
学術雑誌論文
抄録
Pemetrexed (PMX) is a key drug for the management of malignant pleural mesothelioma (MPM). However, its therapeutic efficacy is cruelly restricted in many clinical settings by the overexpression of thymidylate synthase (TS) gene. Recently, we emphasized the efficacy of locally administered shRNA designed against TS gene in enhancing the cytotoxic effect of PMX against orthotopically implanted MPM cells in tumor xenograft tumor model. Herein, we explored the efficiency of systemic, rather than local, delivery of TS RNAi molecule in sensitizing MPM cells to the cytotoxic effect of PMX. We here designed a PEG-coated TS shRNA-lipoplex (PEG-coated TS shRNA-lipoplex) for systemic injection. PEG modification efficiently delivered TS shRNA in the lipoplex to tumor tissue following intravenous administration as indicated by a significant suppression of TS expression level in tumor tissue. In addition, the combined treatment of PMX with systemic injection of PEG-coated TS shRNA-lipoplex exerted a potent antitumor activity in a s.c. xenograft tumor model, compared to a single treatment with either PMX or PEG-coated TS shRNA-lipoplex. Metastasis, or the spread, of mesothelioma substantially dedicates the effectiveness of treatment options. The systemic, in addition to local, delivery of tumor targeted anti-TS RNAi system we propose in this study might be an effective option to extend the clinical utility of PMX in treating malignant mesothelioma.
掲載誌名
Molecular Pharmaceutics
ISSN
15438384
15438392
cat書誌ID
AA11854546
AA12442792
出版者
ACS Publications
13
11
開始ページ
3955
終了ページ
3963
発行日
2016-10-14
権利情報
This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
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
出版社版
部局
薬学系