PMID- 21480204
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20240321
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 117
IP  - 21
DP  - 2011 Nov 1
TI  - Investigation of the insulin-like growth factor-1 signaling pathway in localized 
      Ewing sarcoma: a report from the Children's Oncology Group.
PG  - 4966-76
LID - 10.1002/cncr.26112 [doi]
AB  - BACKGROUND: The insulin-like growth factor-1 (IGF-1) signaling pathway plays an 
      important role in the pathology of Ewing sarcoma (ES). Retrospective studies have 
      suggested that levels of IGF-1 and IGF binding protein 3 (IGFBP-3) are correlated 
      with the outcome of patients with ES. METHODS: The IGF-1 signaling pathway was 
      investigated prospectively in 269 patients who had localized, previously 
      untreated ES. Serum samples were obtained at diagnosis, and concentrations of 
      IGF-1 and IGFBP-3 were determined by enzyme-linked immunosorbent assays. In 
      addition, immunohistochemistry (IHC) was performed to assay for phosphorylated 
      p70S6 kinase, protein kinase B (Akt), and forkhead box protein O1 (FOXO1) and to 
      determine the presence of protein tyrosine phosphatase-L1 (PTPL1). IHC findings 
      along with IGF-1 and IGFBP-3 concentrations were correlated with age, tumor 
      location, sex, event-free survival, and overall survival. RESULTS: Patients aged 
      >18 years tended to have higher levels of IGF-1 (P = .10), lower levels of 
      IGFBP-3 (P = .16), and decreased IGFBP-3:IGF-1 ratios (P = .01). No correlations 
      were observed between sex, tumor location, or outcomes and concentrations of 
      IGF-1 or IGFBP-3. Phosphorylation of p70S6 kinase, Akt, and FOXO1 was detected in 
      the majority of patient tissues but was not associated with age, sex, or tumor 
      location. PTPL1 was present in >80% of tumors and also was not correlated with 
      age, sex, or tumor location. There was no difference in survival with respect to 
      the presence of phosphorylated p70S6 kinase, phosphorylated FOXO1, phosphorylated 
      Akt, or PTPL1. CONCLUSIONS: The baseline IGFBP-3:IGF-1 ratio was correlated with 
      age but did not affect the outcomes of patients with ES. The authors concluded 
      that additional investigation of the IGF-1 pathway is warranted in patients with 
      ES, and especially in those who have received treatment with IGF-1 receptor 
      antibody inhibitors.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Borinstein, Scott C
AU  - Borinstein SC
AD  - Department of Pediatrics, Division of Pediatric Hematology/Oncology, Vanderbilt 
      University, Nashville, Tennessee 20057-1469, USA.
FAU - Barkauskas, Donald A
AU  - Barkauskas DA
FAU - Krailo, Mark
AU  - Krailo M
FAU - Scher, Daniel
AU  - Scher D
FAU - Scher, Lauren
AU  - Scher L
FAU - Schlottmann, Silke
AU  - Schlottmann S
FAU - Kallakury, Bhaskar
AU  - Kallakury B
FAU - Dickman, Paul S
AU  - Dickman PS
FAU - Pawel, Bruce R
AU  - Pawel BR
FAU - West, Daniel C
AU  - West DC
FAU - Womer, Richard B
AU  - Womer RB
FAU - Toretsky, Jeffrey A
AU  - Toretsky JA
LA  - eng
GR  - R01CA138212/CA/NCI NIH HHS/United States
GR  - R01CA133662/CA/NCI NIH HHS/United States
GR  - R01 CA133662/CA/NCI NIH HHS/United States
GR  - U24 CA114766/CA/NCI NIH HHS/United States
GR  - P30 CA051008/CA/NCI NIH HHS/United States
GR  - R01 CA088004/CA/NCI NIH HHS/United States
GR  - R01CA88004/CA/NCI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - RC4CA156509/CA/NCI NIH HHS/United States
GR  - U10 CA98543/CA/NCI NIH HHS/United States
GR  - RC4 CA156509/CA/NCI NIH HHS/United States
GR  - R01 CA138212/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110408
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Child
MH  - Female
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/blood
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Male
MH  - Sarcoma, Ewing/*blood/mortality
MH  - Signal Transduction
PMC - PMC4008340
MID - NIHMS425029
COIS- CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.
EDAT- 2011/04/12 06:00
MHDA- 2011/12/13 00:00
PMCR- 2014/05/02
CRDT- 2011/04/12 06:00
PHST- 2010/12/10 00:00 [received]
PHST- 2011/01/26 00:00 [revised]
PHST- 2011/02/14 00:00 [accepted]
PHST- 2011/04/12 06:00 [entrez]
PHST- 2011/04/12 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2014/05/02 00:00 [pmc-release]
AID - 10.1002/cncr.26112 [doi]
PST - ppublish
SO  - Cancer. 2011 Nov 1;117(21):4966-76. doi: 10.1002/cncr.26112. Epub 2011 Apr 8.