PMID- 21468343
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1177-5483 (Electronic)
IS  - 1177-5467 (Print)
IS  - 1177-5467 (Linking)
VI  - 5
DP  - 2011
TI  - Advanced retinoblastoma treatment: targeting hypoxia by inhibition of the 
      mammalian target of rapamycin (mTOR) in LH(BETA)T(AG) retinal tumors.
PG  - 337-43
LID - 10.2147/OPTH.S16172 [doi]
AB  - PURPOSE: The purpose of this study is to analyze the dose response of the 
      mammalian target of rapamycin (mTOR) inhibitor, rapamycin, on tumor burden and 
      hypoxia, and study the treatment effect on vasculature in LH(BETA)T(AG) retinal 
      tumors. METHODS: This study was approved by the Institutional Animal Care and Use 
      Committee and follows Association for Research in Vision and Ophthalmology 
      guidelines. Eighteen-week-old LH(BETA)T(AG) retinal tumor eyes (n = 30) were 
      evaluated. Mice were divided into five groups and received periocular injections 
      once weekly for two consecutive weeks of: a) 80% DMSO (dimethyl sulfoxide, 
      vehicle control), b) 0.00333 mg/kg, c) 0.167 mg/kg, d) 3.33 mg/kg, and e) 6.67 
      mg/kg of rapamycin. Tumor sections were analyzed for hypoxia, tumor burden, and 
      vasculature with immunohistochemistry techniques. RESULTS: Reduction in tumor 
      burden and hypoxia was significantly different between rapamycin doses and 
      control (P < 0.002). Eyes treated with rapamycin at 0.167, 3.33, and 6.67 mg/kg 
      showed a significant decrease in tumor burden in comparison with the vehicle 
      control group (P = 0.019, P = 0.001, P = 0.009, respectively) and the 0.00333 
      mg/kg dose response (P = 0.023, P = 0.001, P = 0.010, respectively). Eyes treated 
      with rapamycin at 3.33 mg/kg showed a significant reduction in the amount of 
      hypoxia in comparison with the lower concentration groups (0.00333 and 0.167 
      mg/kg) of rapamycin (P = 0.024 and P = 0.052, respectively). The number of mature 
      vessels was significantly lower in the 3.33 mg/kg treated versus vehicle control 
      (P = 0.015; equal variances assumed, t-test for equality of means). The number of 
      neovessels was not significantly different between both groups (P = 0.092). 
      CONCLUSION: Inhibition of mTOR was shown to reduce tumor burden, hypoxia, and 
      vasculature in the LH(BETA)T(AG) retinoblastoma tumor model. Rapamycin may have a 
      role in combination with chemotherapy or other adjuvant therapies to enhance 
      retinoblastoma tumor control.
FAU - Pina, Y
AU  - Pina Y
AD  - Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 
      Miami, FL, USA;
FAU - Decatur, C
AU  - Decatur C
FAU - Murray, Tg
AU  - Murray T
FAU - Houston, Sk
AU  - Houston S
FAU - Gologorsky, D
AU  - Gologorsky D
FAU - Cavalcante, M
AU  - Cavalcante M
FAU - Cavalcante, L
AU  - Cavalcante L
FAU - Hernandez, E
AU  - Hernandez E
FAU - Celdran, M
AU  - Celdran M
FAU - Feuer, W
AU  - Feuer W
FAU - Lampidis, T
AU  - Lampidis T
LA  - eng
GR  - P30 EY014801/EY/NEI NIH HHS/United States
GR  - R01 CA037109/CA/NCI NIH HHS/United States
GR  - R01 EY012651/EY/NEI NIH HHS/United States
GR  - R01 EY013629/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20110307
PL  - New Zealand
TA  - Clin Ophthalmol
JT  - Clinical ophthalmology (Auckland, N.Z.)
JID - 101321512
PMC - PMC3065577
OTO - NOTNLM
OT  - anaerobic glycolysis
OT  - hypoxia
OT  - mTOR
OT  - rapamycin
OT  - retinoblastoma
EDAT- 2011/04/07 06:00
MHDA- 2011/04/07 06:01
PMCR- 2011/03/07
CRDT- 2011/04/07 06:00
PHST- 2011/03/04 00:00 [received]
PHST- 2011/04/07 06:00 [entrez]
PHST- 2011/04/07 06:00 [pubmed]
PHST- 2011/04/07 06:01 [medline]
PHST- 2011/03/07 00:00 [pmc-release]
AID - opth-5-337 [pii]
AID - 10.2147/OPTH.S16172 [doi]
PST - ppublish
SO  - Clin Ophthalmol. 2011;5:337-43. doi: 10.2147/OPTH.S16172. Epub 2011 Mar 7.