PMID- 20929525
OWN - NLM
STAT- MEDLINE
DCOM- 20110321
LR  - 20220309
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 10
DP  - 2010 Oct 7
TI  - Activated mammalian target of rapamycin is a potential therapeutic target in 
      gastric cancer.
PG  - 536
LID - 10.1186/1471-2407-10-536 [doi]
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) plays a key role in cellular 
      growth and homeostasis. The purpose of our present study is to investigate the 
      expression of activated mTOR (p-mTOR) in gastric cancer patients, their 
      prognostic significance and the inhibition effect of RAD001 on tumor growth and 
      to determine whether targeted inhibition of mTOR could be a potential therapeutic 
      strategy for gastric cancer. METHODS: The expression of p-mTOR was detected in 
      specimens of 181 gastric cancers who underwent radical resection (R0) by 
      immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic 
      features and survival of gastric cancer was studied. We also determined the 
      inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric 
      cancer cell lines. RESULTS: Immunostaining for p-mTOR was positive in 93 of 181 
      (51.4%) gastric cancers, closely correlated with lymph node status and pTNM 
      stage. Patients with p-mTOR positive showed significantly shorter disease-free 
      survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative 
      tumors in univariable analyses, and there was a trend toward a correlation 
      between p-mTOR expression and survival in multivariable analyses. RAD001 markedly 
      inhibited dose-dependently proliferation of human gastric carcinoma cells by 
      down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, 
      up-regulating expression of P53. CONCLUSIONS: In gastric cancer, p-mTOR is a 
      potential therapeutic target and RAD001 was a promising treatment agent with 
      inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, 
      CyclinD1 and Bcl-2, up-regulating expression of P53.
FAU - Xu, Da-zhi
AU  - Xu DZ
AD  - State Key Laboratory of Oncology in South China, Guangzhou 510060, China.
FAU - Geng, Qi-rong
AU  - Geng QR
FAU - Tian, Ying
AU  - Tian Y
FAU - Cai, Mu-yan
AU  - Cai MY
FAU - Fang, Xin-juan
AU  - Fang XJ
FAU - Zhan, You-qing
AU  - Zhan YQ
FAU - Zhou, Zhi-wei
AU  - Zhou ZW
FAU - Li, Wei
AU  - Li W
FAU - Chen, Ying-bo
AU  - Chen YB
FAU - Sun, Xiao-wei
AU  - Sun XW
FAU - Guan, Yuan-xiang
AU  - Guan YX
FAU - Li, Yuan-fang
AU  - Li YF
FAU - Lin, Tong-yu
AU  - Lin TY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101007
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
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  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Disease-Free Survival
MH  - Everolimus
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Sirolimus/analogs & derivatives/pharmacology
MH  - Stomach Neoplasms/*metabolism/*surgery
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Treatment Outcome
PMC - PMC2958947
EDAT- 2010/10/12 06:00
MHDA- 2011/03/22 06:00
PMCR- 2010/10/07
CRDT- 2010/10/09 06:00
PHST- 2009/09/20 00:00 [received]
PHST- 2010/10/07 00:00 [accepted]
PHST- 2010/10/09 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2011/03/22 06:00 [medline]
PHST- 2010/10/07 00:00 [pmc-release]
AID - 1471-2407-10-536 [pii]
AID - 10.1186/1471-2407-10-536 [doi]
PST - epublish
SO  - BMC Cancer. 2010 Oct 7;10:536. doi: 10.1186/1471-2407-10-536.