PMID- 18466352
OWN - NLM
STAT- MEDLINE
DCOM- 20091104
LR  - 20211203
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 13
IP  - 7
DP  - 2009 Jul
TI  - RAD001 (everolimus) inhibits tumour growth in xenograft models of human 
      hepatocellular carcinoma.
PG  - 1371-80
LID - 10.1111/j.1582-4934.2008.00364.x [doi]
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and 
      highly resistant to available chemotherapies. Mammalian target of rapamycin 
      (mTOR) functions to regulate protein translation, angiogenesis and cell cycle 
      progression in many cancers including HCC. In the present study, subcutaneous 
      patient-derived HCC xenografts were used to study the effects of an mTOR 
      inhibitor, RAD001 (everolimus), on tumour growth, apoptosis and angiogenesis. We 
      report that oral administration of RAD001 to mice bearing patient-derived HCC 
      xenografts resulted in a dose-dependent inhibition of tumour growth. 
      RAD001-induced growth suppression was associated with inactivation of downstream 
      targets of mTOR, reduction in VEGF expression and microvessel density, inhibition 
      of cell proliferation, up-regulation of p27(Kip1) and down-regulation of 
      p21(Cip1/Waf1), Cdk-6, Cdk-2, Cdk-4, cdc-25C, cyclin B1 and c-Myc. Our data 
      indicate that the mTOR pathway plays an important role in angiogenesis, cell 
      cycle progression and proliferation of liver cancer cells. Our study provides a 
      strong rationale for clinical investigation of mTOR inhibitor RAD001 in patients 
      with HCC.
FAU - Huynh, Hung
AU  - Huynh H
AD  - Laboratory of Molecular Endocrinology, Division of Cellular and Molecular 
      Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 
      Singapore. cmrhth@nccs.com.sg
FAU - Chow, K H Pierce
AU  - Chow KH
FAU - Soo, Khee Chee
AU  - Soo KC
FAU - Toh, Han Chong
AU  - Toh HC
FAU - Choo, Su Pin
AU  - Choo SP
FAU - Foo, Kian Fong
AU  - Foo KF
FAU - Poon, Donald
AU  - Poon D
FAU - Ngo, Van Chanh
AU  - Ngo VC
FAU - Tran, Evelyn
AU  - Tran E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080507
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Body Weight
MH  - Carcinoma, Hepatocellular/blood/*drug therapy
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Proliferation
MH  - Everolimus
MH  - Humans
MH  - Liver Neoplasms/blood/*drug therapy
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Microvessels/pathology
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - Sirolimus/*analogs & derivatives/therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - Vascular Endothelial Growth Factor A/blood
MH  - *Xenograft Model Antitumor Assays
PMC - PMC4496150
EDAT- 2008/05/10 09:00
MHDA- 2009/11/05 06:00
PMCR- 2009/07/01
CRDT- 2008/05/10 09:00
PHST- 2008/05/10 09:00 [pubmed]
PHST- 2009/11/05 06:00 [medline]
PHST- 2008/05/10 09:00 [entrez]
PHST- 2009/07/01 00:00 [pmc-release]
AID - JCMM364 [pii]
AID - 10.1111/j.1582-4934.2008.00364.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2009 Jul;13(7):1371-80. doi: 10.1111/j.1582-4934.2008.00364.x. 
      Epub 2008 May 7.