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N.A. Laurie, M.A. Dyer; New Chemotherapeutic Treatments for Retinoblastoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3195.
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Retinoblastoma, the third most prevalent childhood cancer in children younger than 1 year, can be treated in its early stages with a combination of chemotherapy, laser therapy, and cryotherapy. In its late stages, however, this approach is not as effective.
We are currently testing new chemotherapeutic drugs and drug combinations for the purpose of discovering more effective treatments for retinoblastoma.
We have developed three new animal models that we are using to target these drugs. We are utilizing an orthotopic xenograft model, in which human retinoblastoma cells are injected into the eyes of newborn rats. We are also using an in vivo retroviral model, in which the replication–incompetent retrovirus (LIA–EE1A) encoding the E1A oncogene is injected into the eyes of newborn mice, which leads to the transformation of retinal progenitor cells into clonal focal tumors. Lastly, we have developed a genetic model, involving a conditional triple knock–out in the retina (Rblox/–, p107–/–, p53–/–, Chx10–cre). In vitro, we have tested the effect of chemotherapeutic drugs on cell viability (live/dead assay), proliferation (BrdU), apoptosis (Tunel) (see picture), and cell cycle arrest (FACS). We have also tested the pharmacokinetics of these drugs in the vitreous, retina, and plasma of rats.
We have identified a novel drug combination that is more effective than the current standard triple therapy of etoposide, carboplatin, and vincristine.
Our animal models combined with cell culture and pharmacokinetics is an effective preclinical screen for new treatments.
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