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Background Paediatric neuroblastoma and brain tumours account for a third of all childhood cancer-related mortality. High-risk neuroblastoma is highly aggressive and survival is poor despite intensive multi-modal therapies with significant toxicity. Novel therapies are desperately needed. The Zika virus (ZIKV) can access the nervous system and there is growing interest in employing ZIKV as a potential therapy against paediatric nervous system tumours, including neuroblastoma. Methods Here, we perform extensive data mining, integration and re-analysis of ZIKV infection datasets to highlight molecular mechanisms that may govern the oncolytic response in neuroblastoma cells. We collate infection data of multiple neuroblastoma cell lines by different ZIKV strains from a body of published literature to inform the susceptibility of neuroblastoma to the ZIKV oncolytic response. Integrating published transcriptomics, interaction proteomics, dependency factor and compound datasets we propose the involvement of multiple host systems during ZIKV infection. Results Through data mining of published literature, we observed most paediatric neuroblastoma cell lines to be highly susceptible to ZIKV infection and propose the PRVABC59 ZIKV strain to be the most promising candidate for neuroblastoma oncolytic virotherapy. ZIKV induces TNF signalling, lipid metabolism, the Unfolded Protein Response (UPR), and downregulates cell cycle and DNA replication processes. ZIKV infection is dependent on sterol regulatory element binding protein (SREBP)-regulated lipid metabolism and three protein complexes; V-ATPase, ER Membrane Protein Complex (EMC) and mammalian translocon. We propose ZIKV non-structural protein 4B (NS4B) as a likely mediator of ZIKVs interaction with IRE1-mediated UPR, lipid metabolism and mammalian translocon. Conclusions Our work provides a significant understanding of ZIKV infection in neuroblastoma cells, which will facilitate the progression of ZIKV-based oncolytic virotherapy through pre-clinical research and clinical trials.

Abstract Background Despite complete resection of mature ovarian teratoma, there remains a risk of metachronous contralateral disease with implications for further surgery and fertility. Current estimates of this risk are wide and practice regarding surveillance varies. We aimed to identify the incidence of metachronous contralateral disease in girls presenting with unilateral mature ovarian teratoma and to describe current follow-up. Methods Retrospective case note review was performed for all girls (

Mature ovarian teratoma has the potential to occur metachronously in the contralateral ovary. There are significant implications for fertility as bilateral oophorectomy may be indicated. In prepubertal girls, ovarian tissue cryopreservation (OTC) offers the only possibility of a future biological pregnancy but outcome data are limited. We present a case of prepubertal OTC in a 12-year-old girl undergoing a second oophorectomy for metachronous contralateral mature teratoma. We offer a discussion of the challenges that emerged regarding perioperative decision-making, balancing the need for safe oncological resection with the desire to preserve fertility.