Combination of Carboplatin and Bevacizumab Is an Efficient Therapeutic Approach in Retinoblastoma Patient-Derived Xenografts

Assayag, Franck; André, Nathalie; Vacher, Sophie; Dehainault, Catherine; Bièche, Ivan; Meseure, Didier; Aerts, Isabelle; Cassoux, Nathalie; Houdayer, Claude; Doz, François; Decaudin, Didier

doi:10.1167/iovs.15-18725

Cited by 11 publications

(9 citation statements)

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“…Additionally, molecular suppression or silencing of these targets has the advantage of superior selectivity and lower systemic toxicities compared to chemotherapeutic agents. The use of an anti-VEGF antibody in combination with chemotherapy may enhance the efficacy of chemotherapy toward retinoblastoma [64, 65], despite a distinct toxicity profile in use for clinical trials. Whether a VEGF inhibitor will work effectively in humans and not only in nonhuman or human tumor sample trials needs to be validated as well.…”

Section: Discussionmentioning

confidence: 99%

Clinicohistopathological implications of MMP/VEGF expression in retinoblastoma: a combined meta-analysis and bioinformatics analysis

Zhu

Zhang

et al. 2019

J Transl Med

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Background No in-depth systematic evidence is available for assessing retinoblastoma malignancy and eligibility for subsequent treatment. Methods The Cochrane Library, EMBASE, PubMed, Web of Science, and China Biology Medicine databases were searched, and 16 studies comprising 718 retinoblastoma patients were included. Pooled odds ratios (ORs) and summary correlation coefficients (r) with 95% confidence intervals (CIs) in random-effects, fixed-effects or quality-effects models were calculated using Review Manager 5.3 and MetaXL. GO functional annotation and KEGG pathway analysis were performed using the GO and STRING databases. Results We observed significant associations between high levels of MMP-1 (OR, 4.21; 95% CI 1.86–9.54), MMP-2 (OR, 11.18; 95% CI 4.26–29.30), MMP-9 (OR, 10.41, 95% CI 4.26–25.47), and VEGF (OR, 8.09; 95% CI 4.03–16.20) with tumor invasion; high levels of MMP-1 (OR, 3.58; 95% CI 1.48–8.71), MMP-2 (OR, 2.96; 95% CI 1.32–6.64), MMP-9 (OR, 5.49; 95% CI 3.55–8.48) and VEGF (OR, 5.30; 95% CI 2.93–9.60) with poor differentiation; and overexpression of MMP-9 (OR, 5.17; 95% CI 2.85–9.38) with advanced clinical stages. Moreover, MMP-9 and VEGF expression were positively correlated (r, 0.61; 95% CI 0.38–0.77). Multiple GO terms were enriched associated with MMP-1, MMP-2, MMP-9 and VEGF, and they are closely associated with pathways, proteoglycans and microRNAs related to cancer. Conclusions MMP-1, MMP-2, MMP-9 and VEGF play important roles in the development and progression of retinoblastoma. High levels of MMP-1, MMP-2, MMP-9 and VEGF are credible implications for increased malignancy, thus the need for more aggressive treatments. Electronic supplementary material The online version of this article (10.1186/s12967-019-1975-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Clinicohistopathological implications of MMP/VEGF expression in retinoblastoma: a combined meta-analysis and bioinformatics analysis

Zhu

Zhang

et al. 2019

J Transl Med

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“…Retinoblastoma is a rare pediatric tumor of the Retina that affects around 6,000–8,000 children every year (11, 12). There is currently no targeted therapy for Retinoblastoma (13–16) and many patients suffer secondary tumors (17, 18), or developmental defects, due to treatment. In over 95% of cases, the development of this tumor is driven the homozygous deletion of the Retinoblastoma 1 (RB1) tumor suppressor gene, on chromosome 13p14 (1).…”

Section: Introductionmentioning

confidence: 99%

Non-coding and Coding Transcriptional Profiles Are Significantly Altered in Pediatric Retinoblastoma Tumors

et al. 2019

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Retinoblastoma is a rare pediatric tumor of the retina, caused by the homozygous loss of the Retinoblastoma 1 (RB1) tumor suppressor gene. Previous microarray studies have identified changes in the expression profiles of coding genes; however, our understanding of how non-coding genes change in this tumor is absent. This is an important area of research, as in many adult malignancies, non-coding genes including LNC-RNAs are used as biomarkers to predict outcome and/or relapse. To establish a complete and in-depth RNA profile, of both coding and non-coding genes, in Retinoblastoma tumors, we conducted RNA-seq from a cohort of tumors and normal retina controls. This analysis identified widespread transcriptional changes in the levels of both coding and non-coding genes. Unexpectedly, we also found rare RNA fusion products resulting from genomic alterations, specific to Retinoblastoma tumor samples. We then determined whether these gene expression changes, of both coding and non-coding genes, were also found in a completely independent Retinoblastoma cohort. Using our dataset, we then profiled the potential effects of deregulated LNC-RNAs on the expression of neighboring genes, the entire genome, and on mRNAs that contain a putative area of homology. This analysis showed that most deregulated LNC-RNAs do not act locally to change the transcriptional environment, but potentially function to modulate genes at distant sites. From this analysis, we selected a strongly down-regulated LNC-RNA in Retinoblastoma, DRAIC, and found that restoring DRAIC RNA levels significantly slowed the growth of the Y79 Retinoblastoma cell line. Collectively, our work has generated the first non-coding RNA profile of Retinoblastoma tumors and has found that these tumors show widespread transcriptional deregulation.

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“…In recent years, enucleation has been excluded from the treatment options for RB, and different treatments are adopted according to the different stages of the tumor, aiming to retain the eyes and their functions ( 5 ). Chemoreduction, mainly systemic chemotherapy, has become the first-line approach for the clinical treatment of RB ( 6 , 7 ). It greatly improved the survival rate of the patients without affecting the structure and function of eyeballs.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑106b promotes the proliferation, migration and invasion of retinoblastoma cells by inhibiting the expression of ZBTB4 protein

Wang

Xiangrong

2018

Exp Ther Med

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The present study investigated the function of microRNA (miR)-106b in the proliferation, migration and invasion of retinoblastoma (RB) cells, and aimed to elucidate the underlying mechanism. A total of 56 patients with RB were enrolled in the present study. The expression of miR-106b in RB tissues was measured by reverse transcription quantitative polymerase chain reaction. After transfection with miR-106b mimics or miR-106b inhibitor, a Cell-Counting kit-8 assay was used to determine the proliferation of WERI-Rb-1 cells and a Transwell assay was employed to measure the migration and invasion of the cells. Western blot analysis was performed to determine the expression of zinc finger and BTB domain containing 4 (ZBTB4) protein. By silencing or overexpression of ZBTB4 protein, the biological functions of ZBTB4 in WERI-Rb-1 cells were studied. A dual luciferase reporter assay was performed to test whether ZBTB4 was a target gene of miR-106b. The expression of miR-106b in RB tissues was elevated and closely associated with the severity of the disease. Overexpression of miR-106b increased but inhibition of miR-106b expression decreased the proliferation, migration and invasion abilities of WERI-Rb-1 cells. In addition, overexpression of miR-106b decreased but inhibition of miR-106b expression increased ZBTB4 protein expression in WERI-Rb-1 cells. Similarly, overexpression of ZBTB4 reduced but inhibition of ZBTB4 expression promoted the proliferation, migration and invasion of WERI-Rb-1 cells. Finally, miR-106b regulated the expression of ZBTB4 by binding to the 3′-untranslated region of the ZBTB4 gene. The present study demonstrated that increased expression of miR-106b in RB tissues is positively associated with the metastasis and differentiation of RB cells. As an oncogene, miR-106b promotes the proliferation, migration and invasion of WERI-Rb-1 cells by inhibiting the expression of ZBTB4 protein.

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Combination of Carboplatin and Bevacizumab Is an Efficient Therapeutic Approach in Retinoblastoma Patient-Derived Xenografts

Abstract: Overall, our in vivo results confirm the interest in antiangiogenic therapy for the treatment of Rb in combination with carboplatin and provide a robust rationale for testing this combination in the clinical setting for Rb patients.

Cited by 11 publications

References 55 publications

Clinicohistopathological implications of MMP/VEGF expression in retinoblastoma: a combined meta-analysis and bioinformatics analysis

Clinicohistopathological implications of MMP/VEGF expression in retinoblastoma: a combined meta-analysis and bioinformatics analysis

Non-coding and Coding Transcriptional Profiles Are Significantly Altered in Pediatric Retinoblastoma Tumors

MicroRNA‑106b promotes the proliferation, migration and invasion of retinoblastoma cells by inhibiting the expression of ZBTB4 protein

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