PMID- 23331792
OWN - NLM
STAT- MEDLINE
DCOM- 20130705
LR  - 20211021
IS  - 1531-5037 (Electronic)
IS  - 0022-3468 (Print)
IS  - 0022-3468 (Linking)
VI  - 48
IP  - 1
DP  - 2013 Jan
TI  - Rapamycin increases neuroblastoma xenograft and host stromal derived 
      osteoprotegerin inhibiting osteolytic bone disease in a bone metastasis model.
PG  - 47-55
LID - S0022-3468(12)00871-8 [pii]
LID - 10.1016/j.jpedsurg.2012.10.043 [doi]
AB  - PURPOSE: Osteoprotegerin (OPG) is a decoy receptor for the Receptor of NF-kappaB 
      (RANK) ligand that can inhibit osteoclastogenesis. Previous studies have 
      suggested that Mammalian Target of Rapamycin (mTOR) inhibition upregulates OPG 
      production. We tested the hypothesis that the mTOR inhibitor rapamycin could 
      inhibit neuroblastoma bone metastases through its action on OPG. EXPERIMENTAL 
      DESIGN: An orthotopic model of bone metastasis was established. Mice with 
      established disease were subsequently treated with rapamycin (5mg/kg IP daily) or 
      vehicle control (DMSO 1:1000). X-rays were obtained twice a week to detect 
      pathologic fractures. Serum OPG levels were measured by ELISA after two weeks of 
      treatment. RESULTS: Mice with bone disease receiving rapamycin had increased 
      serum levels of OPG in the CHLA-20 mice compared to controls (36.89 pg/mL +/- 3.90 
      vs 18.4 pg/mL +/- 1.67, p=0.004) and NB1691 tumor-bearing groups (46.03 +/- 2.67 
      pg/mL vs 17.96 +/- 1.84pg/mL, p=0.001), and a significantly longer median time to 
      pathologic fractures with CHLA-20 (103 days vs 74.5 days, p=0.014) and NB1691 
      xenografts. CONCLUSION: In a xenograft model, increased OPG expression correlated 
      with a delay to pathologic fracture suggesting a potential role for mTOR 
      inhibitors in the treatment of neuroblastoma bone metastases.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Hartwich, Joseph E
AU  - Hartwich JE
AD  - Department of Surgery, Virginia Commonwealth University, Richmond, VA 23284, USA.
FAU - Orr, W Shannon
AU  - Orr WS
FAU - Ng, Catherine Y
AU  - Ng CY
FAU - Spence, Yunyu
AU  - Spence Y
FAU - McLaughlin, Jillian M
AU  - McLaughlin JM
FAU - Furman, Wayne L
AU  - Furman WL
FAU - McGregor, Lisa M
AU  - McGregor LM
FAU - Davidoff, Andrew M
AU  - Davidoff AM
LA  - eng
GR  - P01 CA023099/CA/NCI NIH HHS/United States
GR  - P30 CA021765/CA/NCI NIH HHS/United States
GR  - R25 CA023944/CA/NCI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PL  - United States
TA  - J Pediatr Surg
JT  - Journal of pediatric surgery
JID - 0052631
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Biomarkers)
RN  - 0 (Osteoprotegerin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biomarkers/blood
MH  - Bone Neoplasms/blood/complications/*drug therapy/*secondary
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fractures, Spontaneous/etiology/prevention & control
MH  - Humans
MH  - Injections, Intraperitoneal
MH  - Mice
MH  - Mice, SCID
MH  - Neuroblastoma/blood/complications/*drug therapy/*secondary
MH  - Osteoprotegerin/*blood
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sirolimus/*therapeutic use
MH  - Treatment Outcome
PMC - PMC3584337
MID - NIHMS417712
EDAT- 2013/01/22 06:00
MHDA- 2013/07/06 06:00
PMCR- 2014/01/01
CRDT- 2013/01/22 06:00
PHST- 2012/09/19 00:00 [received]
PHST- 2012/10/13 00:00 [accepted]
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/07/06 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - S0022-3468(12)00871-8 [pii]
AID - 10.1016/j.jpedsurg.2012.10.043 [doi]
PST - ppublish
SO  - J Pediatr Surg. 2013 Jan;48(1):47-55. doi: 10.1016/j.jpedsurg.2012.10.043.