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following treatment with 2-fluorodeoxy-D-glucose at 1 day (86%)
and 3 weeks (63%) post-treatment (p≤0.05). There was no reduction
of tumor burden observed when mice were treated with 1 injection
and eyes harvested at 1 week post-treament (2%, p=0.0640). There
was a significant reduction of hypoxia areas following treatment with
2-fluorodeoxy-D-glucose at 1 day (100%) and 3 weeks (75%) posttreatment
(p≤0.05). There was an increase in hypoxia of 12% following
treatment at 1 week post-injection, but this increase was not statistically
significant.
Conclusions. 2-FDG significantly reduces tumor burden and tumor
hypoxia following a single injection, with continued efficacy following
repeated injections for 3 weeks. 2-FDG treatment is efficacious in
murine retinoblastoma tumors and may enhance tumor control when
combined with other therapies. 2-FDG appears to target hypoxic cells,
a population that has been resistant to chemotherapy and radiation.
Additionally, 2-FDG is commonly used in medical imaging and does not
pose significant toxicities.
Financial disclosure
This work was supported by the American Cancer Society and the
University of Miami Sylvester Comprehensive Cancer Center. NIH center
grant P30EY014801 and by an unrestricted grant to the University of
Miami from Research to Prevent Blindness.
2140 Res 27
MTOR TARGETING IN COMBINATION WITH CHEMO-
THERAPY: UPSTREAM REGULATION OF ANAEROBIC
GLYCOLYSIS TO TARGET THE CHEMORESISTANT CELL
POPULATION IN RB
Timothy G. Murray, Yolanda Piña, Christina L. Decatur, Samuel Houston,
Ludimila Cavalcante, and Theodore Lampidis (tmurray@med.miami.edu)
Bascom Palmer Eye Institute, University of Miami Miller School of
Medicine, Miami, Florida, USA.
Purpose. To assess the efficacy of the combination therapy utilizing
carboplatin chemotherapy and rapamycin mammalian target of
RESEARCH DAY
Abstracts
27
rapamycin (mTOR) inhibitor on tumor burden, hypoxia, and blood
vessels in the LHBETATAG transgenic mouse model of retinoblastoma.
Methods. The study protocol was approved by the University of
Miami Institutional Animal Care and Use Review Board Committee. 12week-old
(n=62) LHBETATAG transgenic mice were treated with the
chemotherapeutic agent carboplatin, the mTOR inhibitor rapamycin, or
both. Animals were treated with subconjunctival injections twice a week
and received treatment for either 1 week or 3 weeks. All animals were
sacrificed at 1 day post-last injection and eyes were enucleated. At the
time of enucleation, all eye samples were snap frozen and analyzed for
tumor burden, hypoxia, new blood vessels, and mature blood vessels
using histopathology and immunohistochemistry. Data were statistically
analyzed using ANOVA.
Results. Mice that received treatment for 1 week had a tumor reduction
of 23.8%, 49.3%, and 60.6% when treated with carboplatin, rapamycin,
and carboplatin + rapamycin, respectively (p