Program Book

30 RBp127
TREATMENT MODULATION IN RETINOBLASTOMA TUM-
ORIGENESIS AND ITS IMPACT ON TUMOR BURDEN
Timothy G. Murray, Samuel Houston, Christina L. Decatur, Nikesh Shah,
Ludimila Cavalcante, and Yolanda Piña (tmurray@med.miami.edu)
Bascom Palmer Eye Institute, University of Miami Miller School of
Medicine, Miami, Florida, USA.
Purpose. The Purpose of the current study is to examine vessel targeting,
chemotherapy, and mammalian target of rapamycin (mTOR) inhibitor
agents in LHBETATAG retinal tumors and their impact on tumor burden.
Methods. Group A: Ten-week-old, LHBETATAG mice (n=30) received a
single subconjunctival injection of anecortave acetate (AA; 1200, 600,
300, and 150 µg) delivered to right eyes only. Group B: Ten-week-old,
LHBETATAG mice (n=30) received a single subconjunctival injection of
AA (600, 300, and 150 µg) delivered to right eyes only, either during
a cycle of carboplatin (six subconjunctival deliveries) or after the
completed cycle. Carboplatin was delivered at the subtherapeutic
concentration of 62.5 µg. All animals were euthanatized at 16 weeks of
age, and the eyes were examined histopathologically. Group C: Eighteenweek-old,
LHBETATAG mice received (n=30) subconjunctival injections
of rapamycin once weekly for two consecutive weeks (0.00333, 0.167,
3.33, and 6.67 mg/kg). Tumor sections were analyzed for tumor burden
with immunohistochemistry techniques.
Results. A statistically significant reduction in tumor burden was
detected after a single periocular injection of AA. The reduction of
tumor burden followed a U-shaped dose-response curve. Tumor burden
was significantly decreased when AA and carboplatin were combined.
However, varying doses and delivery schedule of these agents had
significant impact on the effectiveness of the combined treatment.
The most effective scheme was delivering a low dose (150-300 µg) of
AA after a complete cycle of carboplatin. Reduction in tumor burden
were significantly different between rapamycin doses and control
(pA, at the (-23) position of the
intron 9 of the coding sequence of the retinoblastoma gene, RB1. This