المؤلفون: Jia, Shichong, Wen, Xuyang, Yu, Jie, Zhou, Min, Yang, Ludi, Feng, Yiyi, He, Xiaoyu, Jia, Renbing, Fan, Jiayan, Fan, Xianqun

مصطلحات موضوعية: Ocular oncology

الوصف: Aims To investigate the risk factors for cataract following eye-preserving therapies for retinoblastoma. Methods This retrospective, single-centre cohort study included patients diagnosed with retinoblastoma receiving eye-preserving therapies between January 2017 and June 2021. Cataract by the end of the follow-up was the main outcome. Results Cataract was found in 31 of 184 (16.8%) included eyes during a mean follow-up of 27.6 months. The cataract and control groups were similar regarding patients’ laterality, sex and disease stage. Eyes in the cataract group were more likely to present with endophytic retinoblastoma (p=0.02) and greater intraocular pressure (p=0.001). Competing risk regression analysis (univariate Fine-Gray model) showed that the growth pattern (p=0.01), intraocular pressure (p=0.01), number of intra-arterial chemotherapy (IAC) cycles (p=0.001), melphalan dose per IAC cycle (p=0.001) and number of intravitreous chemotherapy (IvitC) cycles (p=0.001) were associated with cataract occurrence. Multivariate analysis included higher intraocular pressure (p=0.003), a higher melphalan dose per IAC cycle (p=0.001) and an increasing number of IvitC cycles (p=0.04) as independent risk factors for cataract. Conclusions Repeated IAC and/or IvitC with melphalan were the most common eye-preserving therapies that induced cataract formation. The toxic effect of melphalan was an essential factor in cataract development, as indicated by the association of cataract occurrence with the melphalan dose.

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العلاقة: http://bjo.bmj.com/cgi/content/short/108/4/571Test; http://dx.doi.org/10.1136/bjo-2022-321723Test

الإتاحة: https://doi.org/10.1136/bjo-2022-321723Test
http://bjo.bmj.com/cgi/content/short/108/4/571Test

المؤلفون: Luo, Yingxiu, Xu, Mingpeng, Yang, Ludi, Yao, Yiran, Berry, Jesse L, Xu, Liya, Wen, Xuyang, He, Xiaoyu, Han, Minglei, Fan, Xianqun, Fan, Jiayan, Jia, Renbing

مصطلحات موضوعية: Ocular oncology

الوصف: Background This study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history. Methods Single-centre retrospective cohort study from including 58 AH samples collected from 58 patients diagnosed. Among them, 41 samples were collected after enucleation and 17 samples were collected before intravitreal chemotherapy. SCNAs were accessed by conducting shallow whole-genome sequencing in cell-free (cf) DNA of AH. HRs and ORs were applied to measure risk factors. Results Canonical RB SCNAs including 1q gain (87%), 2p gain (50%), 6p gain (76%), 16q loss (69%) were frequently detected. Non-classical RB SCNAs in AH including 17q gain (53%), 19q loss (43%), 7q gain (35%) were also commonly observed. 19q loss was significantly more common in patients with cT3c or worse stage than others (p=0.034). 2p gain(p=0.001) and 7q gain(p=0.001) were both more common in patients with primary enucleation than those with previous chemotherapy. Interestingly, both 2p gain (HR=1.933, p=0.027) and 7q gain (HR=2.394, p=0.005) might predict enucleation. Correlation analysis with pathological features among enucleated eyes showed that 19q loss can predict a higher risk for both massive choroid invasion (OR=4.909, p=0.038) and postlaminar optic nerve invasion (OR=4.250, p=0.043). Discussion Sequencing of AH cfDNA in RB can provide sufficient in vivo information. 19q loss was a potential signature of advanced cases clinically and pathologically. Repeated sampling from eyes receiving sequential chemotherapy should be conducted to evaluate fluctuation of SCNA in future study.

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العلاقة: http://bjo.bmj.com/cgi/content/short/108/3/449Test; http://dx.doi.org/10.1136/bjo-2022-322866Test

الإتاحة: https://doi.org/10.1136/bjo-2022-322866Test
http://bjo.bmj.com/cgi/content/short/108/3/449Test

المؤلفون: Zhou, Min, Tang, Jieling, Fan, Jiayan, Wen, Xuyang, Shen, Jianfeng, Jia, Renbing, Chai, Peiwei, Fan, Xianqun

المساهمون: NSFC

المصدر: Asia-Pacific Journal of Ophthalmology ; page 100058 ; ISSN 2162-0989

مصطلحات موضوعية: Ophthalmology, General Medicine

الإتاحة: https://doi.org/10.1016/j.apjo.2024.100058Test
https://api.elsevier.com/content/article/PII:S2162098924000537?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2162098924000537?httpAccept=text/plainTest

المؤلفون: Zuo, Sipeng, Li, Lin, Wen, Xuyang, Gu, Xiang, Zhuang, Ai, Li, Rui, Ye, Fuxiang, Ge, Shengfang, Fan, Xianqun, Fan, Jiayan, Chai, Peiwei, Lu, Linna

المساهمون: National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality

المصدر: Clinical and Translational Medicine ; volume 13, issue 5 ; ISSN 2001-1326 2001-1326

الوصف: Background The precise temporal and spatial regulation of N 5 ‐methylcytosine (m 5 C) RNA modification plays essential roles in RNA metabolism, and is necessary for the maintenance of epigenome homeostasis. Howbeit, the mechanism underlying the m 5 C modification in carcinogenesis remains to be fully addressed. Methods Global and mRNA m 5 C levels were determined by mRNA isolation and anti‐m 5 C dot blot in both retinoblastoma (RB) cells and clinical samples. Orthotopic intraocular xenografts were established to examine the oncogenic behaviours of RB. Genome‐wide multiomics analyses were performed to identify the functional target of NSUN2, including proteomic analysis, transcriptome screening and m 5 C‐methylated RNA immunoprecipitation sequencing (m 5 C‐meRIP‐seq). Organoid‐based single‐cell analysis and gene‐correlation analysis were performed to verify the NSUN2/ALYREF/m 5 C‐PFAS oncogenic cascade. Results Herein, we report that NSUN2‐mediated m 5 C RNA methylation fuels purine biosynthesis during the oncogenic progression of RB. First, we discovered that global and mRNA m 5 C levels were significantly enriched in RBs compared to normal retinas. In addition, tumour‐specific NSUN2 expression was noted in RB samples and cell lines. Therapeutically, targeted correction of NSUN2 exhibited efficient therapeutic efficacy in RB both in vitro and in vivo. Through multiomics analyses, we subsequently identified phosphoribosylformylglycinamidine synthase (PFAS), a vital enzyme in purine biosynthesis, as a downstream candidate target of NSUN2. The reintroduction of PFAS largely reversed the inhibitory phenotypes in NSUN2‐deficient RB cells, indicating that PFAS was a functional downstream target of NSUN2. Mechanistically, we found that the m 5 C reader protein ALYREF was responsible for the recognition of the m 5 C modification of PFAS, increasing its expression by enhancing its RNA stability. Conclusions Conclusively, we initially demonstrated that NSUN2 is necessary for oncogenic gene activation in RB, ...

الإتاحة: https://doi.org/10.1002/ctm2.1273Test

المؤلفون: Jia, Shichong, Wen, Xuyang, Yu, Jie, Zhou, Min, Yang, Ludi, Feng, Yiyi, He, Xiaoyu, Jia, Renbing, Fan, Jiayan, Fan, Xianqun

المساهمون: Shanghai Ninth People’s Hospital Excellent Youth Fund Program, Shanghai Key Clinical Specialty, Shanghai Youth Top-notch Talent Support Program, National Natural Science Foundation of China, Science and Technology Development Fund, Science and Technology Commission of Shanghai, Shanghai Eye Disease Research Center

المصدر: British Journal of Ophthalmology ; page bjophthalmol-2022-321723 ; ISSN 0007-1161 1468-2079

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Sensory Systems, Ophthalmology

الوصف: Aims To investigate the risk factors for cataract following eye-preserving therapies for retinoblastoma. Methods This retrospective, single-centre cohort study included patients diagnosed with retinoblastoma receiving eye-preserving therapies between January 2017 and June 2021. Cataract by the end of the follow-up was the main outcome. Results Cataract was found in 31 of 184 (16.8%) included eyes during a mean follow-up of 27.6 months. The cataract and control groups were similar regarding patients’ laterality, sex and disease stage. Eyes in the cataract group were more likely to present with endophytic retinoblastoma (p=0.02) and greater intraocular pressure (p=0.001). Competing risk regression analysis (univariate Fine-Gray model) showed that the growth pattern (p=0.01), intraocular pressure (p=0.01), number of intra-arterial chemotherapy (IAC) cycles (p=0.001), melphalan dose per IAC cycle (p=0.001) and number of intravitreous chemotherapy (IvitC) cycles (p=0.001) were associated with cataract occurrence. Multivariate analysis included higher intraocular pressure (p=0.003), a higher melphalan dose per IAC cycle (p=0.001) and an increasing number of IvitC cycles (p=0.04) as independent risk factors for cataract. Conclusions Repeated IAC and/or IvitC with melphalan were the most common eye-preserving therapies that induced cataract formation. The toxic effect of melphalan was an essential factor in cataract development, as indicated by the association of cataract occurrence with the melphalan dose.

الإتاحة: https://doi.org/10.1136/bjo-2022-321723Test

المؤلفون: He, Mengjia, Yang, Ludi, Jia, Shichong, Yang, Jie, Wen, Xuyang, Fan, Jiayan, Jia, Renbing, Fan, Xianqun

المصدر: Acta Ophthalmologica (1755375X); May2024, Vol. 102 Issue 3, pe296-e301, 6p

مصطلحات موضوعية: CALCIFICATION, GLAUCOMA, RETINOBLASTOMA, HEMORRHAGE, COMPUTED tomography

مصطلحات جغرافية: PHILADELPHIA (Pa.)

مستخلص: Purpose: To explore whether varying degrees of vitreous haemorrhage (VH) and calcification act as risk factors for enucleation in patients with advanced retinoblastoma (RB). Methods: Advanced RB was defined by the international classification of RB (Philadelphia version). Basic information for retinoblastoma patients diagnosed as groups D and E in our hospital between January 2017 and June 2022 was reviewed by logistics regression models. Additionally, a correlation analysis was performed, excluding variables with a VIF (variance inflation factor) >10 from the multivariate analysis. Results: A total of 223 eyes diagnosed with RB were included in assessing VH and calcification; of these, 101 (45.3%) eyes experienced VH, and 182 (76.2%) eyes were found to have calcification within the tumour through computed tomography (CT) or B‐scan ultrasonography. Ninety‐two eyes (41.3%) were enucleated, of which 67 (72.8%) had VH and 68 (73.9%) calcification, both of which were significantly relevant to enucleation (p < 0.001*). Other clinical risk factors, such as corneal edema, anterior chamber haemorrhage, high intraocular pressure during treatment and iris neovascularization, correlated significantly with enucleation (p < 0.001*). Multivariate analysis included IIRC (intraocular international retinoblastoma classification), VH, calcification and high intraocular pressure during treatment as independent risk factors for enucleation. Conclusions: Despite identifying different potential risk factors for RB, there remains significant controversy concerning which patients require enucleation, and the degree of VH varies. Such eyes need to be evaluated carefully, and management with appropriate adjuvant therapy may improve the outcome of these patients. [ABSTRACT FROM AUTHOR]

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المؤلفون: Wen, Xuyang, Ding, Tianyi, Li, Fang, Fan, Jiayan, Fan, Xianqun, Jia, Renbing, Zhang, He

المصدر: Communications Biology ; volume 5, issue 1 ; ISSN 2399-3642

مصطلحات موضوعية: General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous)

الوصف: RB transcriptional corepressor 1 ( RB1 ) is a critical regulatory gene in physiological and pathological processes. Genetic mutation is considered to be the main cause of RB1 inactivation. However, accumulating evidence has shown that not all RB1 dysfunction is triggered by gene mutations, and the additional mechanism underlying RB1 dysfunction remains unclear. Here, we firstly reveal that a CCCTC binding factor (CTCF) mediated intrachromosomal looping served as a regulatory inducer to inactivate RB1 . Once the core genomic fragment was deleted by Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9), this intrachromosomal looping was disrupted. After the open of chromatin, Enhancer of Zeste Homolog 2 (EZH2) was released and decreased the level of Tri-Methyl-Histone H3 Lys27 (H3K27me3) at the RB1 promoter, which substantially restored the expression of RB protein (pRB) and inhibited tumorigenesis. In addition, targeted correction of abnormal RB1 looping using the small-molecule compound GSK503 efficiently restored RB1 transcription and suppressed tumorigenesis. Our study reveals an alternative transcriptional mechanism underlying RB1 dysfunction independent of gene mutation, and advancing the discovery of potential therapeutic chemicals based on aberrant chromatin looping.

الإتاحة: https://doi.org/10.1038/s42003-022-04007-2Test
https://www.nature.com/articles/s42003-022-04007-2.pdfTest
https://www.nature.com/articles/s42003-022-04007-2Test

المؤلفون: Zeng, Changjuan, Han, Minglei, Fan, Jiayan, He, Xiaoyu, Jia, Renbing, Li, Li, Wen, Xuyang, Song, Xuefei, Hou, Lili

المصدر: Frontiers in Oncology ; volume 12 ; ISSN 2234-943X

الوصف: Background Retinoblastoma (Rb) is a common ocular malignant tumor in children. Intra-arterial chemotherapy (IAC) has been widely used in children with Rb and has achieved an ideal therapeutic effect. However, IAC has side effects, including anemia and bone marrow suppression, for which explicit evidence on the risk factors is lacking. This study aimed to evaluate the covariates that may affect the occurrence of anemia and bone marrow suppression in children with Rb after IAC. Methods Children with Rb admitted between May 2019 and January 2021 were included into the study. The differences in the number of children with anemia and bone marrow suppression before and after IAC according to different covariates were recorded. All potential impact factors were included into the univariate and multivariate regression models to identify the related covariates of post-IAC anemia and bone marrow suppression. Results Data of 282 children with Rb were retrospectively collected. After IAC, children with Rb had increased severities of anemia (p <0.0001, chi-square test) and bone marrow suppression (p = 0.001, chi-square test). Moreover, the number of children with Rb who had an increased cross-level change in the severity of anemia and degree of bone marrow suppression was 80 (41.24%) and 64 (32.49%), respectively. The univariate regression analysis showed that numerous factors (such as pre-IAC intravenous chemotherapy, results of pre-IAC routine blood tests, and some serological indicators for liver and kidney function) affected the anemia severity and degree of bone marrow suppression in children with Rb after IAC. Additionally, the predictive model of the multivariate regression could predict anemia and bone marrow suppression. Conclusion Children with Rb may have an increased risk of anemia and bone marrow suppression after IAC, but this is temporary and can be influenced by several factors. Therefore, IAC should be maintained as the standard of care. We generated predictive equations for predicting anemia severity ...

الإتاحة: https://doi.org/10.3389/fonc.2022.848877Test

المؤلفون: Jia, Shichong, Zhu, Tianyu, Shi, Hanhan, Zong, Chunyan, Bao, Yongyang, Wen, Xuyang, Ge, Shengfang, Ruan, Jing, Xu, Shiqiong, Jia, Renbing, Fan, Xianqun

المصدر: Ophthalmology ; volume 129, issue 7, page 771-780 ; ISSN 0161-6420

مصطلحات موضوعية: Ophthalmology

الإتاحة: https://doi.org/10.1016/j.ophtha.2022.02.029Test
https://api.elsevier.com/content/article/PII:S0161642022001683?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0161642022001683?httpAccept=text/plainTest

المؤلفون: Zhou, Min, Wen, Xuyang, Jia, Shichong, Han, Yanping, He, Xiaoyu, Han, Minglei, Xu, Wei, Fan, Jiayan, Jia, Renbing, Fan, Xianqun

المصدر: British Journal of Ophthalmology ; volume 106, issue 11, page 1581-1586 ; ISSN 0007-1161 1468-2079

الوصف: Purpose To explore the risk factors for ophthalmic artery (OA) stenosis and occlusion after intra-arterial chemotherapy (IAC) with selective ophthalmic artery catheterisation (OAC) in the treatment of retinoblastoma. Design Retrospective, single centre case-control study. Methods The study was conducted including consecutive patients with unilateral or bilateral intraocular retinoblastoma undergoing IAC between June 2016 and June 2019 with a follow-up time of 4 years. Main outcomes are rate of IAC-induced OA occlusion and OA diameter. Results 346 attempted OAC infusions were successful. The total incidence of OA occlusion was 15.89%. The occlusion and control groups were similar in patients’ age, sex and disease stage. Median OA diameter was 0.49 mm in those with OA occlusion, and 0.66 mm in those without occlusion. In the occlusion group, the OA diameter difference was significantly larger between the first IAC and the final IAC (0.22mm vs 0.12mm, p=0.001). In both groups, the median number of IAC treatments was 3. Multivariate Cox regression models included initial OA diameter (OR: 0.005, p=0.001), ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter (OR: 4.661, p=0.003), and number of IAC (OR: 1.538, p=0.042) as clinical features significantly associated with OA occlusion. Conclusions The OA diameter at first IAC treatment, the ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter and total number of IAC treatments may be three main clinical predictors for OA occlusion after IAC for retinoblastoma.

الإتاحة: https://doi.org/10.1136/bjophthalmol-2021-319118Test