Neuroblastoma is unique amongst common pediatric cancers for its expression of the norepinephrine transporter (NET), enabling tumor-selective imaging and therapy with radioactive analogues of norepinephrine. The majority of neuroblastoma tumors are avid for 123I-metaiodobenzaguanidine (mIBG) on imaging, yet the therapeutic response to 131I-mIBG is only 30% in clinical trials, and off-target effects cause short- and long-term morbidity. We review the contemporary understanding of the tumor-selective uptake, retention, and efflux of meta-iodobenzylguanidine (mIBG) and strategies currently in development for improving its efficacy. Combination treatment strategies aimed at enhancing NET are likely necessary to reach the full potential of 131I-mIBG therapy.
Although most high-risk neuroblastomas are responsive to chemotherapy, relapse is common and long-term survival is less than 40%, underscoring the need for more effective treatments. We evaluated the responsiveness of 12 neuroblastoma cell lines to the Δγ134.5 attenuated oncolytic HSV, Seprehvir (HSV1716), which is currently used in pediatric phase I trials. We found that entry of Seprehvir in neuroblastoma cells is independent of the expression of nectin-1 and the sum of all four known major HSV entry receptors. We observed varying levels of sensitivity and permissivity to Seprehvir, suggesting that the cellular anti-viral response, not virus entry, is the key determinant of efficacy with this virus. In vivo, we found significant anti-tumor efficacy following Seprehvir treatment, which ranged from 6/10 complete responses in the CHP-134 model to a mild prolonged median survival in the SK-N-AS model. Taken together, these data suggest that anti-tumor efficacy cannot be solely predicted based on in vitro response. Whether or not this discordance holds true for other viruses or tumor types is unknown. Our results also suggest that profiling the expression of known viral entry receptors on neuroblastoma cells may not be entirely predictive of their susceptibility to Seprehvir therapy.
Purpose: To report photokeratitis caused by the improper use of germicidal lamps purchased during the COVID-19 pandemic. Methods: Case series. Results: Seven patients presented with acute ocular surface pain after exposure to UV-emitting germicidal lamps. Visual acuity was 20/30 or better in 13 of 14 eyes (93%). Anterior segment examination revealed varying degrees of conjunctival injection and diffusely distributed punctate epithelial erosions (PEEs) in every patient. No intraocular inflammation was identified across the cohort and all fundus examinations were normal. Treatment varied by provider and included artificial tears alone or in combination with antibiotic ointments and/or topical steroids. Five patients were followed via telehealth, one patient returned for an in-office visit, and one patient was lost to follow-up. Five of six patients endorsed complete resolution of symptoms within 2-3 days. Conclusions: Patients should follow manufacturer recommendations when using UV-emitting germicidal lamps and avoid direct exposure to the ocular surface.
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