-
Scientific Reports Mar 2022The purpose of this study is to characterize demographically and genetically the Portuguese population with retinoblastoma; to report the clinical stage at presentation... (Observational Study)
Observational Study
The purpose of this study is to characterize demographically and genetically the Portuguese population with retinoblastoma; to report the clinical stage at presentation and its impact on survival and ocular preservation rate and, finally, to assess the incidence of retinoblastoma in Portugal. Retrospective observational study including children consecutively diagnosed with retinoblastoma at the Portuguese National Referral Center of Intraocular Tumors, between October 2015 and October 2020. Twenty-eight children were diagnosed with retinoblastoma at our center, 15 hereditary from which 12 presented with bilateral retinoblastoma and 3 were unilateral. The overall mean age at diagnosis was 13.6 ± 11.1 months with hereditary retinoblastomas diagnosed slightly earlier at 9.6 ± 6.3 months. A familial history of retinoblastoma was found in only 4 (14.3%) of the cases. A pathogenic mutation in the RB1 gene was found in 13 (46.4%) of the children. The most frequent sign at referral was leukocoria in 71.4% of patients. Considering the ICRB classification of the tumors, 84.6% of non-hereditable hereditary retinoblastomas were referred to our center in advanced stages. In the group of hereditable retinoblastomas 86.7% presented with one of the eyes with advanced intraocular retinoblastoma. Fourteen children had one eye enucleated due to retinoblastoma. No deaths were registered during the study period. Considering the incidence analysis, we registered a year-of-birth controlled incidence analysis of 4.04 per 100.000 living births (IC 95% 1.59-6.49). This is the first characterization of the Portuguese Population diagnosed with Retinoblastoma in the National Reference Center.
Topics: Child, Preschool; Genes, Retinoblastoma; Humans; Infant; Portugal; Retinal Neoplasms; Retinoblastoma; Retrospective Studies
PubMed: 35288594
DOI: 10.1038/s41598-022-08326-6 -
Indian Journal of Ophthalmology Aug 2021
Topics: Eye Neoplasms; Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 34304162
DOI: 10.4103/ijo.IJO_1801_21 -
Journal of Occupational and... Mar 2021Retinoblastoma is the most common primary intraocular tumor affecting children. We examine the role of parental occupational exposures and risk of retinoblastoma among...
OBJECTIVE
Retinoblastoma is the most common primary intraocular tumor affecting children. We examine the role of parental occupational exposures and risk of retinoblastoma among offspring.
METHODS
Our population-based case-control study linked data from four nationwide Danish registries and included all cases of retinoblastoma diagnosed in Danish children (<5 y, n = 144) between 1975 and 2014. We focused on two biologically relevant time periods: 90 days preconception to conception for fathers; conception to birth for mothers. Parents were grouped into major industry headings created from Danish industry codes.
RESULTS
We observed increased risk of all retinoblastoma for children of fathers in the food and drink industry and iron and metal industry. Bilateral disease was associated with paternal work in manufacturing and land transportation.
CONCLUSION
Our results suggest that some occupational exposures may increase the risk of childhood sporadic retinoblastoma.
Topics: Case-Control Studies; Denmark; Fathers; Female; Humans; Male; Occupations; Retinal Neoplasms; Retinoblastoma; Risk Factors
PubMed: 33395168
DOI: 10.1097/JOM.0000000000002120 -
Journal of Cellular Physiology Mar 2021Retinoblastoma is the most common intraocular cancer with metastatic potential affecting infants and children. Although chemotherapy is available for retinoblastoma,...
Retinoblastoma is the most common intraocular cancer with metastatic potential affecting infants and children. Although chemotherapy is available for retinoblastoma, side effects and drug resistance are frequent. Rpl41, encoding ribosomal protein L41 (RPL41), has been identified as a tumor suppressor gene, and its targeted degradation of activating transcription factor 4 (ATF4) produces an antitumor effect. The goal of the present study is to provide experimental evidence for the clinical application of a small peptide regimen in combination with chemotherapy for the treatment of retinoblastoma and to investigate the mechanism of their combined cytotoxicity. It was observed that treatment with the RPL41 peptide alone decreased the viability, migration, and invasion of retinoblastoma Y79 and Weri-Rb1 cells, in addition to promoting cell apoptosis and cell cycle arrest. Furthermore, RPL41 protein levels showed a significantly decreased trend in retinoblastoma specimens, whereas ATF4 protein levels tended to be increased. Mechanistically, ATF4 degradation as a result of RPL41 peptide treatment was observed in retinoblastoma Y79 and Weri-Rb1 cells. Most important, low-dose administration of the RPL41 peptide significantly enhanced the antitumor effect of carboplatin, and further analysis confirmed their synergistic effect as anti-retinoblastoma therapy, indicating that RPL41 sensitized Y79 and Weri-Rb1 retinoblastoma cells to carboplatin. Thus, our data provide a preclinical rationale for the exploration of the RPL41 peptide as a potential adjuvant to carboplatin treatment in retinoblastoma.
Topics: Activating Transcription Factor 4; Antineoplastic Agents; Apoptosis; Carboplatin; Cell Line, Tumor; Cell Movement; G1 Phase Cell Cycle Checkpoints; Humans; Neoplasm Invasiveness; Peptides; Proteolysis; Retinoblastoma; Ribosomal Proteins
PubMed: 32783256
DOI: 10.1002/jcp.30010 -
Investigative Ophthalmology & Visual... Dec 2023Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple short- and...
PURPOSE
Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple short- and long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation.
METHODS
Orbital tumor, bone marrow, cerebrospinal fluid, and lymph node tumor infiltration specimens were obtained from seven patients with metastatic retinoblastoma at diagnosis, disease progression, or relapse. Tumor specimens were engrafted in immunodeficient animals, and primary cell lines were established. Genomic, immunohistochemical/immunocytochemical, and pharmacological analysis were performed.
RESULTS
We successfully established five primary cell lines: two derived from leptomeningeal, two from orbital, and one from lymph node tumor dissemination. After the intravitreal or intraventricular inoculation of these cells, we established cell-derived xenograft models. Both primary cell lines and xenografts accurately retained the histological and genomic features of the tumors from which they were derived and faithfully recapitulated the dissemination patterns and pharmacological sensitivity observed in the matched patients.
CONCLUSIONS
Ours is an innovative and thoroughly characterized preclinical platform of metastatic retinoblastoma developed for the understanding of tumor biology of this highly aggressive tumor and has the potential to identify drug candidates to treat patients who currently lack effective treatment options.
Topics: Animals; Humans; Retinoblastoma; Neoplasm Recurrence, Local; Cell Line; Disease Models, Animal; Retinal Neoplasms
PubMed: 38117242
DOI: 10.1167/iovs.64.15.27 -
Journal of Cancer Research and... 2022Retinoblastoma is the most common primary intraocular malignancy of childhood. The present study was undertaken to overcome the scarcity of data regarding the... (Review)
Review
BACKGROUND
Retinoblastoma is the most common primary intraocular malignancy of childhood. The present study was undertaken to overcome the scarcity of data regarding the epidemiology, demographic and clinical profile, and nature of the first health-care professional consulted.
MATERIALS AND METHODS
A retrospective analysis of medical records was performed for all cases of retinoblastoma who presented to the department of ophthalmology and oncology between 2010 and 2017. A total of 54 cases were reviewed.
RESULTS
Unilateral disease was seen in 85.2% while 14.8% presented with bilateral disease with a median age of 3 years and 2 years, respectively, at diagnosis. The male: female ratio was 2:1. The most common presenting symptom was leukocoria which was noticed in 42 patients (77.7%), followed by red eye (33.3%) and proptosis (20.3%). The most common stage of presentation was Stage I (44.4%), followed by Stage IV (20.4%), Stage III (9.3%), and Stage II (5.6%). The median time to diagnosis was 8.7 months (range, 0.5-98.7 months), and the median time to treatment was 37.4 days (range, 0-645 days). Majority of the patients were referred by local ophthalmologists (48%), followed by general practitioners (20%), nurses (19%), and quacks (13%). Enucleation was the most preferred treatment modality (48.1%), followed by chemotherapy (33.3%), radiotherapy (13%), photocoagulation (3.7%), and exenteration (1.9%). The overall remission rate was 79.6%, while 12.3% had relapse and 7.4% died.
CONCLUSION
The study showed a dire need for timely detection and treatment of retinoblastoma which is possible with improved awareness and better accessibility to health-care facilities. It also revealed a decrease in histopathological risk factors with chemoreduction.
Topics: Child, Preschool; Female; Humans; Male; India; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Retinal Neoplasms; Retinoblastoma; Retrospective Studies
PubMed: 36412421
DOI: 10.4103/jcrt.JCRT_1263_20 -
Acta Ophthalmologica Feb 2022To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening.
METHODS
We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis.
RESULTS
Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs.
CONCLUSIONS
An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.
Topics: Brain Neoplasms; Early Diagnosis; Humans; Infant; Magnetic Resonance Imaging; Pineal Gland; Pinealoma; Retinal Neoplasms; Retinoblastoma
PubMed: 33939299
DOI: 10.1111/aos.14855 -
Ophthalmology Jun 2022
Topics: Humans; Retina; Retinal Neoplasms; Retinoblastoma; Tomography, Optical Coherence
PubMed: 35598905
DOI: 10.1016/j.ophtha.2021.11.012 -
European Journal of Ophthalmology Nov 2021Most cases of retinoblastoma are diagnosed before the age of 5 years. The cases in older age groups can have variable presentations leading to misdiagnosis and...
Most cases of retinoblastoma are diagnosed before the age of 5 years. The cases in older age groups can have variable presentations leading to misdiagnosis and management challenges. We report a case of retinoblastoma in an 8-year-old female who was primarily referred as a case of sympathetic ophthalmia due to a co-incidental misleading history of penetrating eye injury to other eye 3 weeks prior. The patient complained of decreased vision in the left eye after 3 weeks of repair of the corneo-scleral laceration in the right eye. Visual acuity in the right and left eye was 3/60 and light perception respectively. The anterior segment examination showed moderate sized keratic precipitates, intense inflammatory cellular reaction with large fluffy cells, hypopyon and dense vitreous exudates. Ultrasonography showed abundant hyperechoic contents within the vitreous cavity in the left globe. The retino-choroid was thickened. The possibility of endophthalmitis and sympathetic ophthalmia was considered. Diagnostic vitrectomy was planned. Intraoperatively, after clearing the exudates, a yellowish white mass lesion was seen superiorly. Post- operatively contrast-enhanced MRI scan confirmed the presence of an enhancing mass lesion in the globe consistent with the diagnosis of intraocular retinoblastoma. Enucleation of left globe was done after chemotherapy. Thus, a high risk of suspicion has to be kept for this malignant tumour in children with unexplained visual loss.
Topics: Child; Eye Injuries, Penetrating; Female; Humans; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitrectomy
PubMed: 32613860
DOI: 10.1177/1120672120939388 -
Anti-cancer Drugs Jun 2022Retinoblastoma is a familial inherited embryonic neuroretinal malignancy with a low survival rate and poor prognosis. Our study aimed to evaluate the potential...
Retinoblastoma is a familial inherited embryonic neuroretinal malignancy with a low survival rate and poor prognosis. Our study aimed to evaluate the potential interaction between microRNA miR-657 and the peroxisome proliferator-activated receptor alpha (PPARA) in retinoblastoma. Expression of miR-657 and PPARA was analyzed in retinoblastoma tissues and cells using RT-qPCR. Cell proliferation, apoptosis, and migration were measured in retinoblastoma cell lines, and xenografting experiments were performed using nude mice. Our study showed that miR-657 expression was markedly increased, whereas that of PPARA was markedly decreased in retinoblastoma. Additionally, PPARA knockdown enhanced the development of retinoblastoma. miR-657 enhanced the retinoblastoma tumorigenesis by directly inhibiting PPARA expression, suggesting that PPARA targeting by miR-657 facilitates retinoblastoma development by enhancing cell growth. This study provides novel insights into the miR-657- and PPARA-mediated mechanisms underlying retinoblastoma progression and suggests that the interaction between miR-657 and PPARA may serve as an effective target for therapeutic intervention.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Mice; Mice, Nude; MicroRNAs; PPAR alpha; Retinal Neoplasms; Retinoblastoma
PubMed: 35324527
DOI: 10.1097/CAD.0000000000001308