The RB1 Story: Characterization and Cloning of the First Tumor Suppressor Gene.

The RB1 gene is the first described human tumor suppressor gene and plays an integral role in the development of retinoblastoma, a pediatric malignancy of the eye. Since its discovery, the stepwise characterization and cloning of RB1 have laid the foundation for numerous advances in the understanding of tumor suppressor genes, retinoblastoma tumorigenesis, and inheritance. Knowledge of RB1 led to a paradigm shift in the field of cancer genetics, including widespread acceptance of the concept of tumor suppressor genes, and has provided crucial diagnostic and prognostic information through genetic testing for patients affected by retinoblastoma. This article reviews the long history of RB1 gene research, characterization, and cloning, and also discusses recent advances in retinoblastoma genetics that have grown out of this foundational work

Long-Term Outcomes of Group B Eyes in Patients with Retinoblastoma Treated with Short-Course Chemoreduction: Experience from Children's Hospital Los Angeles/University of Southern California

BACKGROUND/AIMS: Chemoreduction protocols for retinoblastoma vary widely across institutions. Herein, we compare a 3- versus 6-cycle chemotherapy approach for group B retinoblastoma. METHODS: A nonrandomized, retrospective review of patients diagnosed with group B retinoblastoma from 1991-2011 at Children's Hospital Los Angeles was performed. A total of 72 eyes of 63 patients were analyzed. Mean follow-up time was 82 months (range 6-272 months). Main outcome measures were globe salvage and need for external beam radiation. RESULTS: Forty-six patients (55 eyes) were treated upfront with 3 cycles of carboplatin, etoposide, and vincristine; 17 patients (17 eyes) received 6 cycles. Thirty-seven eyes (67%) in the 3-cycle group were cured with initial chemoreduction alone. An additional 10 eyes with persistent or recurrent tumors were rescued with 3 more cycles for a total salvage rate of 85% (47/55 eyes). In the 6-cycle group, 16 of 17 eyes (94%) avoided radiation and enucleation. CONCLUSION: The initial recurrence rate was higher for the 3-cycle group (p = 0.03). However, eyes failing short-course chemoreduction were rescued with 3 additional cycles and achieved a similar overall event-free survival rate (p = 0.16). In our cohort, this short-course approach spared 63% (29/46) of patients with group B retinoblastoma the extra 3 cycles of systemic chemotherapy

Sonoporation Enhances Chemotherapeutic Efficacy in Retinoblastoma Cells In Vitro

Sonoporation, a technique by which ultrasound is combined with diagnostic microbubbles to enhance the intracellular uptake of drugs, is shown to enhance the delivery, and thus the efficacy, of chemotherapy against retinoblastoma cells in vitro