PMID- 22333597
OWN - NLM
STAT- MEDLINE
DCOM- 20120418
LR  - 20211203
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 106
IP  - 5
DP  - 2012 Feb 28
TI  - Aberrant activation of the mTOR pathway and anti-tumour effect of everolimus on 
      oesophageal squamous cell carcinoma.
PG  - 876-82
LID - 10.1038/bjc.2012.36 [doi]
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) protein is important for 
      cellular growth and homeostasis. The presence and prognostic significance of 
      inappropriate mTOR activation have been reported for several cancers. Mammalian 
      target of rapamycin inhibitors, such as everolimus (RAD001), are in development 
      and show promise as anti-cancer drugs; however, the therapeutic effect of 
      everolimus on oesophageal squamous cell carcinoma (OSCC) remains unknown. 
      METHODS: Phosphorylation of mTOR (p-mTOR) was evaluated in 167 resected OSCC 
      tumours and 5 OSCC cell lines. The effects of everolimus on the OSCC cell lines 
      TE4 and TE11 in vitro and alone or in combination with cisplatin on tumour growth 
      in vivo were evaluated. RESULTS: Mammalian target of rapamycin phosphorylation 
      was detected in 116 tumours (69.5%) and all the 5 OSCC cell lines. Everolimus 
      suppressed p-mTOR downstream pathways, inhibited proliferation and invasion, and 
      induced apoptosis in both TE4 and TE11 cells. In a mouse xenograft model 
      established with TE4 and TE11 cells, everolimus alone or in combination with 
      cisplatin inhibited tumour growth. CONCLUSION: The mTOR pathway was aberrantly 
      activated in most OSCC tumours. Everolimus had a therapeutic effect both as a 
      single agent and in combination with cisplatin. Everolimus could be a useful 
      anti-cancer drug for patients with OSCC.
FAU - Hirashima, K
AU  - Hirashima K
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
FAU - Baba, Y
AU  - Baba Y
FAU - Watanabe, M
AU  - Watanabe M
FAU - Karashima, R-I
AU  - Karashima RI
FAU - Sato, N
AU  - Sato N
FAU - Imamura, Y
AU  - Imamura Y
FAU - Nagai, Y
AU  - Nagai Y
FAU - Hayashi, N
AU  - Hayashi N
FAU - Iyama, K-I
AU  - Iyama KI
FAU - Baba, H
AU  - Baba H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120214
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antineoplastic Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Q20Q21Q62J (Cisplatin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Squamous Cell/*drug therapy/metabolism/pathology
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cisplatin/*pharmacology
MH  - Esophageal Neoplasms/*drug therapy/metabolism/pathology
MH  - Everolimus
MH  - Humans
MH  - Mice
MH  - Phosphorylation
MH  - Sirolimus/*analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC3305959
COIS- The authors declare no conflict of interest.
EDAT- 2012/02/16 06:00
MHDA- 2012/04/19 06:00
PMCR- 2013/02/28
CRDT- 2012/02/16 06:00
PHST- 2012/02/16 06:00 [entrez]
PHST- 2012/02/16 06:00 [pubmed]
PHST- 2012/04/19 06:00 [medline]
PHST- 2013/02/28 00:00 [pmc-release]
AID - bjc201236 [pii]
AID - 10.1038/bjc.2012.36 [doi]
PST - ppublish
SO  - Br J Cancer. 2012 Feb 28;106(5):876-82. doi: 10.1038/bjc.2012.36. Epub 2012 Feb 
      14.