PMID- 18492014
OWN - NLM
STAT- MEDLINE
DCOM- 20090601
LR  - 20131121
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Linking)
VI  - 29
IP  - 3
DP  - 2009 Mar
TI  - Phosphorylation of p70S6 kinase predicts overall survival in patients with clear 
      margin-resected hepatocellular carcinoma.
PG  - 399-405
LID - 10.1111/j.1478-3231.2008.01798.x [doi]
AB  - BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitors play a key 
      role in regulating signal transduction by blocking the mTOR pathway and combining 
      anticancer and immunosuppressive properties. This study was undertaken to 
      determine the prevalence and clinicopathological relevance of phospho-p70S6 
      (p-p70S6) kinase in hepatocellular carcinoma (HCC) and to investigate the effects 
      of rapamycin on HCC in vitro. METHODS: A total of 196 patients with HCCs were 
      treated either with surgical resection (n=106) or liver transplantation (n=90). 
      Tumour tissue was investigated for p-p70S6, phospho-AKT, Ki-67, Cyclin-D1 and 
      apoptosis, and staining results were correlated with clinicopathologically 
      relevant parameters. RESULTS: Overall, p-p70S6 was detected in 24.5% (48/196) of 
      HCCs. In the resection group, 26.4% (28/106) of HCC were positive and 22.2% 
      (20/90) in the transplant group. p-p70S6 was significantly associated with 
      elevated Cyclin-D1 immunoexpression and was correlated with decreased overall 
      survival (P=0.011) in patients resected with a clear margin. In multivariate COX 
      regression analysis, p-p70S6 was identified as an independent prognostic 
      parameter in patients resected with a clear margin. Rapamycin induced apoptosis 
      and growth inhibition by G0/G1 cell cycle arrest in vitro. However, in HCC 
      patients p-p70S6 kinase was not associated with proliferation or apoptosis. 
      CONCLUSIONS: Activation of p70S6 kinase indicates aggressive tumour behaviour in 
      patients with clear margin-resected HCC. Identification of p-p70S6 kinase in HCC 
      selects high-risk patients who may benefit from drugs targeting the mTOR pathway.
FAU - Baba, Hideo A
AU  - Baba HA
AD  - Institute of Pathology and Neuropathology, University Hospital of Essen, 
      University of Duisburg-Essen, Essen, Germany. hideo.baba@uk-essen.de
FAU - Wohlschlaeger, Jeremias
AU  - Wohlschlaeger J
FAU - Cicinnati, Vito R
AU  - Cicinnati VR
FAU - Hilgard, Philip
AU  - Hilgard P
FAU - Lang, Hauke
AU  - Lang H
FAU - Sotiropoulos, Georgios C
AU  - Sotiropoulos GC
FAU - Takeda, Atsushi
AU  - Takeda A
FAU - Beckebaum, Susanne
AU  - Beckebaum S
FAU - Schmitz, Klaus J
AU  - Schmitz KJ
LA  - eng
PT  - Journal Article
DEP - 20080519
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Immunosuppressive Agents)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Carcinoma, Hepatocellular/*metabolism/pathology/surgery
MH  - Cyclin D1/metabolism
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/*pharmacology
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Microarray Analysis
MH  - Phosphorylation/drug effects
MH  - Prognosis
MH  - Regression Analysis
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/*pharmacology
MH  - Survival Analysis
EDAT- 2008/05/22 09:00
MHDA- 2009/06/02 09:00
CRDT- 2008/05/22 09:00
PHST- 2008/05/22 09:00 [pubmed]
PHST- 2009/06/02 09:00 [medline]
PHST- 2008/05/22 09:00 [entrez]
AID - LIV1798 [pii]
AID - 10.1111/j.1478-3231.2008.01798.x [doi]
PST - ppublish
SO  - Liver Int. 2009 Mar;29(3):399-405. doi: 10.1111/j.1478-3231.2008.01798.x. Epub 
      2008 May 19.