Objective To investigate the possible mechanism of arsenic trioxide (As2O3) inducing P16 gene demethylation and transcription regulation in the retinoblastoma (RB) Cell Line Y79． Methods The induced growth inhibition of Y79 cell was assayed by MTT; The DNA content of Y79 cell was analyzed by flow cytometry after being exposed to As2O3; the methylation status of the P16 gene in Y79 cell line before and after treatment with As2O3 was detected by the nestedmethylation specific PCR and DNA sequencing; the mRNA of P16,DNA methyltransferases (DNMT3A and 3B)gene were determined by RT-PCR． Results As2O3 was able to inhibit the growth of Y79 cell and increase the cell number in G0-G1 phase；P16 gene was not expressed in Y79 cell line and As2O3 can induce itrsquo;s mRNA expression；after 48 hour disposal of As2O3，the methylation levelof P16 gene was apparently attenuated in Y79 cell line,the expression of DNMT3A and DNMT3B was obviously down-regulated． Conclusions P16 gene is the hypermethylation in the retinoblastoma cell line Y79, and As2O3 can inhibite the methylation of P16 gene and upregulate the expression of p16 gene mRNA which inhibits the proliferation of Y79 cell by inducing the G0-G1 arrest, by inhibiting the expression of DNA methyltransferases.
We have studied the radiosenstivity of retinoblastoma cell [inc: HXO Rb~4,and found that the ceil growth reduced markedly after being treated by 3GyT-ray. From both clone for mation method and MTT assay,we identify that HXO-Rb44 cell is radiosensitive to T-ray.Oxygen can increase the radiosensitivity of HXO-Rb44 cell, but decrease the repair of sublethal damage.Oxygen enchaneement ratio(OER)is 2.77~3.01. （Chin J Ocul Fundus Dis,1994,10:217-219）
Objective To investigate the correlation of expression of Fas/Fas ligand (FasL) and apoptosis in retinoblastoma (RB)． Methods The expression and distribution of Fas/FasL were detected by using immunohistochemical staining in 32 cases of RB． Light microsc opy (32 cases), electron microscopy (4 cases) and TdT mediated biotin-d UTP nick-end labeling (TUNEL) (12 cases) were used to study apoptosis in RB． Results Apoptotic RB cells mostly located at RB regress area． Chromatin margination and apoptotic bodies were found in RB． TUNEL posi tive labeling cells especially located in tumor regress area． Positive immunola beling for Fas and FasL was found in all RB specimens． There was a highly signi ficant and positive correlation between the expression of Fas/FasL and apoptotic indices (AI) (Plt;0.01 or 0.001)． Conclusion The results suggest that apoptotic cell death is prevalent in RB and it may be one type of the most dominant cell death． Fas system may play an important role in oncogenesis and progression of RB, and the up-regulation of Fas system expression might induce RB cell apoptosis． (Chin J Ocul Fundus Dis, 2001,17:21-23)
Objective A short-term observation study of ocular surgery with or without systemic chemotherapy to treat retinoblastoma (RB). Method The clinical data of 66 RB cases treated at Beijing Tongren Hospital from August 2006 to September 2007 were retrospective reviewed.All patients received ultrasound (B scan/CDI), radiology examination (CT scan/MRI) and RetCam retina examination, and classified according to the International Intraocular Retinoblastoma Classification (IIRC) method. Focal therapies (include laser and cryotherapy) were applied to Group A, systemic chemotherapy (CCTV protocol, Cyclosporine, Carboplatin, Teneposide and Vincrinstine) plus ocular surgery (include focal therapy, enucleation and orbital exenteration) to Group B, C, D and E. Patients were followedup for more than 6 months. Result Of 66 cases (36 male/30 female), 16/66 cases were bilateral RB and 50/66 were unilateral. Follow up period was from 6 to 13 months (mean time 8.6 month). According to IIRC, there were 5 eyes in Group A, 6 eyes in Group B, 5 eyes in Group C, 15 eyes in Group D and 51 eyes in Group E( include extraocular disease). 22/82 eyes were conserved at the end of follow up, including 5/5(100%) of group A, 6/6(100%) of group B, 5/5(100%) of Group C, 4/15(26.7%) of Group D and 2/51(3.9%) of Group E. 5/66 (7.6%) patients died during this period, they all were in Group E. Conclusion Ocular surgery combined with systemic chemotherapy is an effective method to treat retinoblastoma. The consequences depends on the classification with higher conservative rate of eyeballs in early and middle stage (Group A, B, C), and lower rate in late stage (Group D and E).
Objective To observe the expression of matrix metalloproteinase（MMP-2, MMP-9 and vascular endothelial growth factor (VEGF) in retinoblastoma (RB) and its relationship with the differentiation and optic nerve infiltration of RB.Methods Forty paraffin specimens of pathological confirmed RB were studied. They were divided into differentiated group (15 cases) and undifferentiated group (25 cases) , optic nerve infiltration group（13 cases） and without optic nerve infiltration group（27 cases）. The expression of MMP-2, MMP-9 and VEGF were detected by immunohistochemistry, their relationships with the differentiation and optic nerve infiltration were also analyzed.Results The positive rate of MMP-2, MMP-9 and VEGF expression in 40 RB cases were 52.5％，57.5％ and 72.5% respectively．The expression of MMP-2, MMP-9 and VEGF in the undifferentiated group were significantly higher than those in the differentiated group (chi;2=9.037, 9.253, 8.095; P＜0.05). The expression of MMP-2, MMP-9 and VEGF in RB with optic nerve infiltration group were significantly higher than those in RB without optic nerve infiltration group (chi;2=11.045,10.243, 8.956；P＜0.05). The expression of MMP-2，MMP-9 had a positive correlation with the expression of VEGF in RB (r=0.126,0.314；P＜0.05). Conclusions MMP-2, MMP-9 and VEGF expressed in RB tumor tissues. The expression of MMP-2, MMP-9 has a positive correlation with the expression of VEGF. The levels of MMP-2, MMP-9 and VEGF expression are related to optic nerve infiltration of RB cells.
ObjectiveTo evaluate the efficacy of intra-arterial chemotherapy (IAC) for advanced retinoblastoma (RB) after failure of intravenous chemotherapy (IVC). MethodsFifteen eyes of 13 patients with advanced RB were treated with IAC (1-5 cycles) after failure of IVC (2-8 cycles). The patients included 10 boys and 3 girls, with the mean age of (15.67±8.16) months. Six patients had bilateral RB and 7 patients had unilateral RB. There were 14 eyes (93.33%) in stage D, 1 eye (6.67%) in stage E according to the International Classification of intraocular retinoblastoma. The main reasons for failure of IVC were recurrent primary tumor in 3 eyes (20.00%), subretinal seeds recurrence in 9 eyes (60.00%), viable vitreous seeds in 2 eyes (13.33%) and poor response of primary tumor in 1 eye (6.67%). The mean interval between IVC completion and IAC start was 3 months. The mean follow-up was 19 months (ranged from 3 to 52 months). ResultsAfter IVC and secondary IAC, the retinoblastoma and seeds were regressed in 12 eyes (80.00%). Three eyes required enucleation for severe vitreous seeds, subretinal seeds recurrence and primary tumor recurrence. There was no evidence of metastasis in any case. ConclusionIAC can achieve high global salvage rate (80.00%) for patients with advanced retinoblastoma after failure of IVC.
Nowadays, one of the most challenging aspects of retinoblastoma (RB) therapy is how to control the resistant or recurrent viable vitreous seeds, for which intravenous chemotherapy appears to be ineffective. Recently, intravitreal chemotherapy offers another option to control advanced stage and vitreous seeds of RB, and may be a promising new approach to RB therapy. However, intravitreal injection for RB patients raises considerable controversy due to concerns of possible extraocular extension along the injection route, and should not replace the primary standard of care for bilateral RB or group E eyes of RB. Close follow-up and further studies are needed to determine appropriate indications, to determine the effective drugs and concentrations, to optimize RB therapy protocols and to investigate the relationship between long-term efficacy and toxicities.
ObjectiveTo understand the current status, research hotspots, and future trends in the field of retinoblastoma (RB). MethodsUsing the Web of Science Core Collection SSCI and SCI-Expanded as data sources, relevant RB literature from January 2015 to November 2024 was retrieved. The bibliometric analysis software CiteSpace 6.2.R6 was employed to perform visual analyses of countries/regions, institutions, journals, authors, co-cited references, and keywords. ResultsA total of 5 042 relevant publications were identified. Annual publication numbers in this field consistently exceeded 400, peaking at 565 in 2021. The United States contributed the highest number of publications, with 1 600 articles (31.73%). Among institutions, Harvard University ranked first with 167 publications (3.31%). Abramson DH of Memorial Sloan Kettering Cancer Center published the most papers (75). Nature (United Kingdom) received the highest citation count (2 349). The highest betweenness centrality was observed for the United States (0.14) among countries/regions, Shanghai Jiao Tong University (0.21) among institutions, and Berry JL of Children’s Hospital Los Angeles (0.21) at the author level. Co-citation and keyword analyses revealed that RB research hotspots are shifting from a focus on basic molecular mechanisms, such as the cell cycle and RB protein, toward advanced therapeutic strategies, such as intra-arterial chemotherapy and nanoparticle-based drug delivery. Emerging keywords such as complexity, chemoresistance and carboplatin indicate that future studies will focus on optimising diagnosis and treatment. ConclusionsFrom 2015 to 2024, RB research displayed a sustained growth trend, with the United States and its institutions and scholars contributing the most publications. The research focus has shifted from the exploration of molecular mechanisms to the optimization of precise treatment strategies, among which the application of nanotechnology and the resolution of drug resistance mechanisms will become key breakthrough directions.
Objective To observe the expression and relationship of high-mobility group A(HMGA)1, HMGA2, MIB-1 labeling index (LI) and let-7 in retinoblastoma (RB). Methods Forty-four RB samples were studied, including 11 poorly-differentiated samples, 33 well-differentiated samples; eight invasive and 36 non-invasive samples. The expression of HMGA1, HMGA2 and MIB-1 LI in RB were analyzed by immunohistochemitry. The HMGA1, HMGA2 were scored on a scale of 0 to high expression. 0: no expression; low: 1%-10%; medium: 11%-50%; high: ＞50%. The MIB LI were scored on a scale of 0 to high expression. 0: no expression; low: 1%-40%; high: ＞40%. Semiquantitative reverse transcription-polymerase chain reaction was used to assay the let-7 expression level: ge;80% showed no significantly decreased expression; 60%-79% showed medium decrease in expression; ＜60% highly decreased in expression. ResultsIn 44 RB samples, there were 14 cases with no HMGA1 expression (32%), 11 cases with low expression (25%), 10 cases with medium expression (23%), and nine cases with high expression (20%). Expression level of HMGA1 was significantly higher in poorly differentiated RB than in well-differentiated RB (chi;2=11.3,P＜0.01); however, no statistically significant difference was found between invasive tumors and noninvasive tumors (chi;2=5.9,P＞0.05). There were 11 cases with no HMGA2 expression (25%), 11 cases with low expression (25%), nine cases with medium expression (20%), and 13 cases with high expression (30%). Expression level of HMGA2 was significantly higher in poorly differentiated and invasive RB than in well-differentiated and noninvasive RB respectively (chi;2=20.9, 8.7;P＜0.05). There were 4 cases with no MIB-1 LI expression (9%), 18 cases with low expression (41%), and 22 cases with high expression (50%). Expression level of MIB-1 LI was significantly higher in poorly differentiated RB than in well-differentiated RB (t=5.2,P＜0.05). Higher expression of MIB-1 LI was found in invasive tumors than in noninvasive tumors, with no significant difference (t=-1.1,P＞0.05). Twenty-seven cases had no significantly decreased expression of let-7 (61%). There were eight cases with medium decreased expression (18%) and nine cases with highly decreased expression (21%). Correlation analyses revealed that MIB-1 LI expression significantly correlated with HMGA1and HMGA2 proteins (r=0.327, 0.602;P＜0.05). A significantly inverse correlation existed between let-7 expression and HMGA1, HMGA2 proteins and MIB-1 LI respectively (r=-0.247,-0.310,-0.392;P＜0.05). Conclusions Overexpression of HMGA1, HMGA2 and MIB-1 LI and down regulation of let-7 were demonstrated in RB. Supplying let-7 to RB cells can possibly inhibit HMGA1 and HMGA2 expression.
PURPOSE: To produce monoclonal antibodies directed against tumor-associated antigens expressed of retinoblastoma-derived tissue culture cell line SO-RBS0. METHODS:Hybridization was performed and the specificity of the antibody was tested by immunofluorescent and immunohistochemical methods. RESULTS:Two hybridomas secreted specific monoclonal antibody against retinoblastoma cells were produced ,and the isotype of the monoclonal antibody was IgG2a CONCLUION:The monoclonal antibodies were specific and highly active against retinoblastoma cells and might be used as immunoconjugate.