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ID 51441
フルテキストURL
著者
Nishikawa, Toshio Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Takaoka, Munenori Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Ohara, Toshiaki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Tomono, Yasuko Shigei Med Res Inst
Hao, Huifang Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Bao, Xiaohong Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Fukazawa, Takuya Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Wang, Zhigang Inner Mongolia Univ, Coll Life Sci, Dept Biol
Sakurama, Kazufumi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Fujiwara, Yasuhiro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Motoki, Takayuki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Shirakawa, Yasuhiro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Yamatsuji, Tomoki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Tanaka, Noriaki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Fujiwara, Toshiyoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
Naomoto, Yoshio Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
抄録
Esophageal squamous cell carcinoma (ESCC) remains one of the most aggressive cancers with poor prognosis regardless of a several reports that indicate a better therapeutic efficacy using some new chemotherapeutic agents. Recent drug development has contributed to an improved specificity to suppress mTOR activity by which many types of malignancies can be explosively progressed. Temsirolimus (CCI-779, TricelTM) is one of recently synthesized analogs of rapamycin and has provided better outcomes for patients with renal cell carcinoma. In this study, we experimentally evaluated an efficacy of targeting mTOR by temsirolimus for ESCC treatment, with an assessment of its survival advantage using an advanced ESCC animal model. First, we confirmed that the expression of phosphorylated mTOR was increased in 46 of 58 clinical ESCC tumor tissues (79.3%) and appeared to get strengthened with tumor progression. All of ESCC cell lines used in this study revealed an increase of mTOR phosphorylation, accompanied with the upregulation of hypoxia inducible factor-I alpha (HIF-1 alpha), one of the critical effectors regulated by mTOR. Temsirolimus treatment apparently suppressed the activation of mTOR and its downstream effectors, resulting in the reduced ability of ESCC cell proliferation. Finally, the weekly administration of temsirolimus significantly diminished the size of subcutaneous tumors (vehicle, 3261.6 +/- 722.0; temsirolimus, 599.2 +/- 122.9; p = 0.007) in nude mice and effectively prolonged orthotopic esophageal cancer-bearing mice (median survival periods: control, 31 d; temsirolimus, 43 d; p = 0.0024). These data suggests that targeting mTOR by temsirolimus may become a therapeutic alternative for esophageal cancer, with a contribution to a better outcome.
キーワード
temsirolimus
esophageal cancer
mTOR
prolonged survival
molecular-targeted therapy
発行日
2013-03
出版物タイトル
Cancer Biology & Therapy
14巻
3号
出版者
Landes Bioscience
開始ページ
230
終了ページ
236
ISSN
1538-4047
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.4161/cbt.23294
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/51446
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT