ABSTRACT
Objective To observe the clinical characteristics of rhegmatogenous retinal detachment (RRD) secondary to conservative therapy in retinoblastoma (RB) patients.Methods A retrospective study. From July 2013 to May 2017, 20 RRD patients (20 eyes) of 456 RB patients (573 eyes) treated in Xinhua Hospital of Shanghai Jiao Tong University School of Medicine were included in the study. Eleven patients (11 eyes) were boy and 9 patients (9 eyes) were girls. Thirteen patients demonstrated bilateral RB and 7 patients had unilateral RB. Average age when diagnosed with RB was 25 months. International Classification of Retinoblastoma groups were C in 1 eye, D in 17 eyes, and E in 2 eyes. These patients received intra-arterial chemotherapy (17 eyes), intravenous chemotherapy (11 eyes), intravitreal chemotherapy (8 eyes), laser (14 eyes) and/or cryotherapy (5 eyes). Twelve patients (12 eyes) received vitreoretinal surgery including vitrectomy (6 eyes) and scleral buckling (7 eyes). The mean follow-up was 39 months. Fundus examination was performed under general anesthesia during comprehensive treatment and follow-up. The time interval of fundus examination varied from 1 to 6 months depending on the stability of the tumor.Results RRD was noted in 20 eyes (3.5％) with RB. Retinal hole was found in 15 eyes (75％). The cause of RRD was atrophic hole in calcified tumor (6 eyes, 30％), cryotherapy-related hole (5 eyes, 25％) and laser-related hole (9 eyes, 45％). Multiple atrophic hole in calcified tumor was noted in 3 eyes. Size of hole smaller than 2 DD was noted in 8 eyes (53％), and larger than 2 DD was noted in 7 eyes (47％). Holes were in posterior (3 eyes), equator (2 eyes) and periphery (10 eyes). Severe proliferated was noted in 1 eye. No tear was found. No bulbar retinal detachment and choroidal detachment was noted. Among 12 eyes who underwent vitreoretinal surgery, reattachment was achieved in 9 eyes (75％). No metastasis was noted.Conclusions Calcified regression of tumor, cryotherapy and laser were main reasons of RRD. Most of the holes are small in diameter and located in the periphery.
ABSTRACT
Objective: To investigate the effect of cobalt chloride (CoCl2) on transgene expression and viral particle titers in tumor cells infected by conditionally replicating adenovirus expression vector with hypoxia response elements(HRE)-regulated E1AE1B expression (Ad-5HRE-E1AE1B-RFP) and non-HRE regulated replication-deficient adenovirus expression vector (Ad-EGFP, Ad-Luc) in vitro and in vivo. Methods: Ad-5HRE-E1AE1B-RFP had five duplicated HRE and mini CMV acted as a promoter to drive E1AE1B expression and constitutive expression of RFP as reporter. The hypoxia model was optimized by exposing tumor cells to different concentrations of CoCl2. The hypoxia-inducible factor 1 alpha (HIF-1α) protein expression was determined by Western blotting. Under the optimized hypoxia model, the positive expression of exogenous gene and virus replication of Ad-5HRE-E1AE1B-RFP or Ad-EGFP-infected tumor cells were examined by conversed microscopic observation, FACS analysis and plaques formation test. Furthermore, transgene expression induced by combined application of hypoxia-inducible replicative adenovirus and replication deficient adenovirus (Ad-Luc) was also evaluated by examining the lucifererse activity in xenografted tumor models in nude mice by micro PET. Results: Western blotting results showed that CoCl2 at 0.4 and 0.08 μg/mL could stabilize and acumulate HIF-1α protein in gastric cancer SGC7901 cells, which could better mimic hypoxia condition. The microscopic observation and FACS analysis showed that CoCl2 at 0.4 μg/mL could remarkably increase the transduction efficacy of Ad-5HRE-E1AE1B-RFP, which was verified by significant increase in the percentage of positive expression of exogenous gene RFP and fluorescence intensity. But plaques formation test showed that Ad-5HRE-E1AE1B-RFP had no replication. CoCl2 0.4 μg/mL augmented the tranduction efficacy and expression levels of non-HRE regulated replication deficient adenovirus Ad-EGFP and Ad-Luc. Combined intratumoral injection of Ad-5HRE-E1AE1B-RFP and Ad-Luc significantly increased the expression of Ad-Luc in nude mice.Conclusion: CoCl2 markedly enhances transgene expression of recombinant adenovirus. However, the underlying mechanism is not only related to the CoCl2-induced hypoxia, but also probably related to regulation of gene transcription.