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Critical Reviews in Oncogenesis 2015Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor... (Review)
Review
Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor susceptibility gene (RB1). Whole-genome sequencing has made it possible to identify secondary genetic lesions following RB1 inactivation. One of the major discoveries from retinoblastoma sequencing studies is that some retinoblastoma tumors have stable genomes. Subsequent epigenetic studies showed that changes in the epigenome contribute to the rapid progression of retinoblastoma following RB1 gene inactivation. In addition, gene amplification and elevated expression of p53 antagonists, MDM2 and MDM4, may also play an important role in retinoblastoma tumorigenesis. The knowledge gained from these recent molecular, cellular, genomic, and epigenomic analyses are now being integrated to identify new therapeutic approaches that can help save lives and vision in children with retinoblastoma, with fewer long-term side effects.
Topics: Animals; Child; Epigenomics; Gene Amplification; Genetic Therapy; Humans; Retinoblastoma; Retinoblastoma Protein
PubMed: 26349417
DOI: 10.1615/critrevoncog.2015013711 -
Indian Journal of Ophthalmology Jun 2017Orbital extension is a major cause of death in children with retinoblastoma in the developing countries. Delayed detection and inappropriate management contribute to... (Review)
Review
Orbital extension is a major cause of death in children with retinoblastoma in the developing countries. Delayed detection and inappropriate management contribute to poor outcome. Conventional treatment including primary orbital exenteration or chemotherapy or radiotherapy alone result in mortality as high as 70%. The recent understanding on the role of sequential multimodal therapy with a combination of high-dose chemotherapy, followed by appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has helped dramatically improve life salvage.
Topics: Combined Modality Therapy; Developing Countries; Humans; Morbidity; Retinal Neoplasms; Retinoblastoma; Survival Rate
PubMed: 28643706
DOI: 10.4103/ijo.IJO_352_15 -
Radiology Jun 2023Background -amplified wild-type () retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance...
Background -amplified wild-type () retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with retinoblastoma and age-matched children with subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing ( status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with retinoblastoma and 88 control children with retinoblastoma. Children in the group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; = .011) with irregular margins (in 16 of 22 children; specificity, 70%; = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; < .001). retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; = .008). Conclusion retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 See also the editorial by Rollins in this issue.
Topics: Humans; Retinoblastoma; N-Myc Proto-Oncogene Protein; Retrospective Studies; Case-Control Studies; Retinal Neoplasms; Ubiquitin-Protein Ligases; Retinoblastoma Binding Proteins
PubMed: 37191489
DOI: 10.1148/radiol.222264 -
Nature Communications Sep 2021Retinoblastoma is the most frequent intraocular malignancy in children, originating from a maturing cone precursor in the developing retina. Little is known on the...
Retinoblastoma is the most frequent intraocular malignancy in children, originating from a maturing cone precursor in the developing retina. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using multi-omics data, we demonstrate the existence of two retinoblastoma subtypes. Subtype 1, of earlier onset, includes most of the heritable forms. It harbors few genetic alterations other than the initiating RB1 inactivation and corresponds to differentiated tumors expressing mature cone markers. By contrast, subtype 2 tumors harbor frequent recurrent genetic alterations including MYCN-amplification. They express markers of less differentiated cone together with neuronal/ganglion cell markers with marked inter- and intra-tumor heterogeneity. The cone dedifferentiation in subtype 2 is associated with stemness features including low immune and interferon response, E2F and MYC/MYCN activation and a higher propensity for metastasis. The recognition of these two subtypes, one maintaining a cone-differentiated state, and the other, more aggressive, associated with cone dedifferentiation and expression of neuronal markers, opens up important biological and clinical perspectives for retinoblastomas.
Topics: Biomarkers, Tumor; Cell Dedifferentiation; Child, Preschool; DNA Methylation; Female; Gene Expression; Genetic Heterogeneity; Humans; Infant; Male; Mutation; N-Myc Proto-Oncogene Protein; Neoplasm Metastasis; Retinal Cone Photoreceptor Cells; Retinal Ganglion Cells; Retinal Neoplasms; Retinoblastoma
PubMed: 34552068
DOI: 10.1038/s41467-021-25792-0 -
Indian Journal of Ophthalmology Jun 2019Intra-arterial chemotherapy (IAC), also known as superselective ophthalmic artery chemotherapy or chemosurgery, is currently widely accepted as one of the primary... (Review)
Review
Intra-arterial chemotherapy (IAC), also known as superselective ophthalmic artery chemotherapy or chemosurgery, is currently widely accepted as one of the primary treatment modalities for intraocular retinoblastoma worldwide. Following the introduction of the technique in 1998, IAC has evolved over the past decades to be safer and more effective. Accumulated evidence shows that IAC is more effective in providing eye salvage in group D and E retinoblastoma as compared to conventional systemic intravenous chemotherapy (IVC). In contrast to IVC, IAC has the added benefits of reduced overall treatment duration and minimal systemic toxicity. This review provides a comprehensive update on the history, technique, indications, contraindications, and outcome of IAC. We have also identified the strengths, weaknesses, opportunities and threats (SWOT analysis) of the technique in this review.
Topics: Antineoplastic Agents; Humans; Injections, Intra-Arterial; Ophthalmic Artery; Retinal Neoplasms; Retinoblastoma
PubMed: 31124482
DOI: 10.4103/ijo.IJO_866_19 -
The Kaohsiung Journal of Medical... Mar 2022Retinoblastoma, also known as ocular cancer, usually affects children under the age of five. The standard of care for managing early-stage retinoblastoma is a...
Retinoblastoma, also known as ocular cancer, usually affects children under the age of five. The standard of care for managing early-stage retinoblastoma is a combination of vincristine, carboplatin, and etoposide. However, this combination-based modality has limited applications owing to its side and late effects. Moreover, in advanced tumor stages, nearly 50% of patients would suffer a partial or full loss of vision. Therefore, therapies that preserve vision and reduce side effects are urgently required. Here, we focused mainly on the common loss-of-function (LOF) mutation of retinoblastoma gene 1 (RB1) in advanced retinoblastoma and investigated the synthetic lethality between RB1-LOF and Aurora kinase inhibition. We showed that Aurora kinase A inhibition could lead to cell mitotic abnormality and apoptosis, and demonstrated in vivo efficacy in a mouse model xenografted with RB1-deficient retinoblastoma. Our findings provide a promising druggable molecular target and potential clinical strategy for tackling retinoblastoma disease.
Topics: Animals; Antineoplastic Agents; Apoptosis; Aurora Kinase A; Cell Line, Tumor; Disease Models, Animal; Female; Genes, Retinoblastoma; Humans; Loss of Function Mutation; Mice, Inbred BALB C; Mice, Nude; Mitosis; Retinal Neoplasms; Retinoblastoma; Mice
PubMed: 34741392
DOI: 10.1002/kjm2.12469 -
Trends in Molecular Medicine Oct 2016Retinoblastoma is a rare childhood cancer of the developing retina, and studies on this orphan disease have led to fundamental discoveries in cancer biology.... (Review)
Review
Retinoblastoma is a rare childhood cancer of the developing retina, and studies on this orphan disease have led to fundamental discoveries in cancer biology. Retinoblastoma has also emerged as a model for translational research for pediatric solid tumors, which is particularly important as personalized medicine expands in oncology. Research on retinoblastomas has been combined with the exploration of retinal development and retinal degeneration to advance a new model of cell type-specific disease susceptibility termed 'cellular pliancy'. The concept can even be extended to species-specific regeneration. This review discusses the remarkable path of retinoblastoma research and how it has shaped the most current efforts in basic, translational, and clinical research in oncology and beyond.
Topics: Animals; Child; Humans; Precision Medicine; Regenerative Medicine; Retina; Retinal Neoplasms; Retinoblastoma; Translational Research, Biomedical
PubMed: 27567287
DOI: 10.1016/j.molmed.2016.07.010 -
International Journal of Public Health 2023To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB. Following the PRIMSA... (Meta-Analysis)
Meta-Analysis Review
To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB. Following the PRIMSA guideline, 14 studies reporting HPV infection in RB acquired from six databases were included. The prevalence of HPV from 941 RB samples was 15.6% [95% confidence interval (CI): 7.3-30]. Mexico followed by India and Brazil had the highest HPV prevalence in RB samples, 61.7% (95% CI: 17-93), 22.5% (95% CI: 9-47), and 12.1% (95% CI: 2-52), in order. HPV 16 was the most common genotype presented in RB samples 23% (95% CI: 9-47), followed by HPV 18 10% (95% CI: 3-30) and the combined HPV 16-18 6% (95% CI: 0-50). We did not find a significant association between HPV and RB [odds ratio (OR): 12.2; 95% CI: 0.65-232; = 0.09]. However, after removing the largest-weighted study, a significant association between HPV and RB was observed (OR: 45.9; 95% CI; 8.6-245; < 0.001). HPV prevalence in RB samples was 15% and HPV 16 was the most presented genotype in RB samples. There may be an association between HPV and RB that is needed to be confirmed by high quality future studies. Preventive and treatment measures against HPV infection are essential for the prevention of any possible consequences, in particular, RB.
Topics: Humans; Retinoblastoma; Papillomavirus Infections; Human Papillomavirus Viruses; Cross-Sectional Studies; Human papillomavirus 16; Prevalence; Retinal Neoplasms
PubMed: 37497122
DOI: 10.3389/ijph.2023.1605284 -
Molecules and Cells Oct 2022Carboplatin-based chemotherapy is the primary treatment option for the management of retinoblastoma, an intraocular malignant tumor observed in children. The aim of the...
Carboplatin-based chemotherapy is the primary treatment option for the management of retinoblastoma, an intraocular malignant tumor observed in children. The aim of the present study was to establish carboplatin-resistant retinoblastoma cell lines to facilitate future research into the treatment of chemoresistant retinoblastoma. In total, two retinoblastoma cell lines, Y79 and SNUOT-Rb1, were treated with increasing concentrations of carboplatin to develop the carboplatin-resistant retinoblastoma cell lines (termed Y79/CBP and SNUOT-Rb1/CBP, respectively). To verify resistance to carboplatin, the degree of DNA fragmentation and the expression level of cleaved caspase-3 were evaluated in the cells, following carboplatin treatment. In addition, the newly developed carboplatin-resistant retinoblastoma cells formed intraocular tumors more effectively than their parental cells, even after the intravitreal injection of carboplatin. Interestingly, the proportion of cells in the G0/G1 phase was higher in Y79/CBP and SNUOT-Rb1/CBP cells than in their respective parental cells. In line with these data, the expression levels of cyclin D1 and cyclin D3 were decreased, whereas p18 and p27 expression was increased in the carboplatin-resistant cells. In addition, the expression levels of genes associated with multidrug resistance were increased. Thus, these carboplatin-resistant cell lines may serve as a useful tool in the study of chemoresistance in retinoblastoma and for the development potential therapeutics.
Topics: Antineoplastic Agents; Carboplatin; Caspase 3; Cell Line, Tumor; Child; Cyclin D1; Cyclin D3; Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 36047446
DOI: 10.14348/molcells.2022.2014 -
Eye (London, England) Apr 2020A retrospective case series describing the clinical features and treatment outcomes in eye with cavitary retinoblastoma.
AIM
A retrospective case series describing the clinical features and treatment outcomes in eye with cavitary retinoblastoma.
METHODS
Case records of patients diagnosed with cavitary retinoblastoma from 2013 to 2017 were reviewed and their demographic details, clinical presentation, and treatment outcomes were analysed.
RESULTS
Thirteen tumours from ten eyes of ten patients were included. Mean age at diagnosis was 36 months (median = 30, range = 2-60 months). Mean number of cavities per tumour were two (median 1, range 1-5). Sixty-two percent of tumours had primary cavities, 23% had secondary cavities, while 15% had both types. Mean basal tumour diameter at presentation was 10.9 mm, and at final follow-up was 10.4 mm. Mean tumour thickness at presentation was 7.7 mm, and at final follow-up was 6.5 mm. Majority of tumours (46%) showed type 2 regression pattern. Tumour recurrence was noted in 1(8%) eye. Cavity rupture with release of vitreous seeds was observed in one eye. Two (20%) eyes with vitreous seeds were treated with intravitreal chemotherapy. Two eyes were advised enucleation, one due to tumour recurrence and the other due to persistent vitreous seeds. No patients had metastasis or death. Mean follow-up was 54 months (median 20, SD 66.82, range 3-183).
CONCLUSION
Cavitary tumours have variable presentations, are often associated with vitreous seeds, and in some cases the latter emanates from them as well. Cavitary tumours tend to maintain stable tumour dimensions.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Humans; Infant; Neoplasm Recurrence, Local; Retinal Neoplasms; Retinoblastoma; Retrospective Studies
PubMed: 31534184
DOI: 10.1038/s41433-019-0581-1