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International Ophthalmology Clinics 2008
Review
Topics: Child, Preschool; Humans; Infant; Retinal Neoplasms; Retinoblastoma
PubMed: 18427266
DOI: 10.1097/IIO.0b013e3181693670 -
Oncology (Williston Park, N.Y.) Apr 1989Retinoblastoma is an uncommon ocular tumor of childhood which accounts for 5% of childhood blindness. It serves as a prototype for understanding the genetics of... (Review)
Review
Retinoblastoma is an uncommon ocular tumor of childhood which accounts for 5% of childhood blindness. It serves as a prototype for understanding the genetics of childhood cancer. The identification of the retinoblastoma gene has provided an explanation for the differing features of hereditary and nonhereditary retinoblastoma, as well as the potential for secondary malignancies in the hereditary cases. Management decisions are based upon the potential for useful vision, and the extent of disease including whether one or both eyes are involved. As nearly all patients present with disease confined to the globe, local control is excellent and survival exceeds 85%. Goals of management are cure of the disease, preservation of vision, and early detection and treatment of secondary malignancies in the genetically susceptible group.
Topics: Biology; Child; Eye Neoplasms; Humans; Retinoblastoma
PubMed: 2701417
DOI: No ID Found -
Critical Reviews in Oncogenesis 1991The retinoblastoma gene (RB) is the prototype of a class of genes, called tumor suppressor genes, for which loss-of-function mutations are oncogenic. Such genes would... (Review)
Review
The retinoblastoma gene (RB) is the prototype of a class of genes, called tumor suppressor genes, for which loss-of-function mutations are oncogenic. Such genes would then normally function to suppress or prevent tumor formation. Classical genetic and cytogenetic studies of retinoblastoma, a rare childhood eye cancer, laid a fundamental groundwork for the molecular cloning of this gene. Surprisingly, mutations of RB are found not only in retinoblastomas but also in some osteosarcomas, soft-tissue sarcomas, and carcinomas of breast, lung, prostate or bladder, suggesting a broad role for RB in human oncogenesis. In support of this hypothesis, a wild-type copy of RB is able to suppress the neoplastic properties of several types of tumor cells with mutated endogenous RB alleles. The RB gene product, pp110RB, is a nuclear phosphoprotein with DNA binding activity. RB protein is cyclically phosphorylated and dephosphorylated during the cell division cycle, and may play a significant role in its regulation.
Topics: Amino Acid Sequence; Genes, Retinoblastoma; Humans; Molecular Sequence Data; Retinoblastoma
PubMed: 1888791
DOI: No ID Found -
European Journal of Ophthalmology Nov 2021Differing techniques have been reported for focal laser therapy for patients with small and medium retinoblastoma. We report the technique used at our center; and report...
PURPOSE
Differing techniques have been reported for focal laser therapy for patients with small and medium retinoblastoma. We report the technique used at our center; and report the functional and anatomical outcomes for small and medium retinoblastomas treated with focal laser therapy with or without systemic chemotherapy.
METHODS
A retrospective case study was conducted including pediatric patients with macular retinoblastoma treated with systemic chemotherapy and laser ablation from July 1990 to July 2015 at Washington University School of Medicine/Saint Louis Children's Hospital.
RESULTS
Fourteen eyes (11 patients) with small and medium retinoblastoma tumors were treated with repetitive indirect laser hyperthermia and seven of those patients were treated with systemic chemotherapy as well. Using the International Retinoblastoma classification, one eye was stage A, 10 eyes were stage B, and three eyes were stage C. The mean follow-up time was 7.7 years. There were no recurrences of tumor in the patients. Final visual acuity outcomes were 20/20 to 20/50 in four eyes, 20/60 to 20/200 in four eyes, and 20/400 or less in six eyes. None of the patients developed metastatic disease.
CONCLUSIONS
The evidence for systemic chemotherapy and diode laser therapy is limited to case series and retrospective reviews, but evidence suggests that it is an effective treatment for small and medium sized retinoblastoma tumors involving the macula with the potential for good visual outcomes.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Humans; Infant; Iris; Lasers, Semiconductor; Retinal Neoplasms; Retinoblastoma; Retrospective Studies
PubMed: 33530736
DOI: 10.1177/1120672121991390 -
Anticancer Research Sep 2020Despite advances in treatment modalities, the visual prognosis of retinoblastoma still remains unsatisfactory, underscoring the need to develop novel therapeutic...
BACKGROUND/AIM
Despite advances in treatment modalities, the visual prognosis of retinoblastoma still remains unsatisfactory, underscoring the need to develop novel therapeutic approaches.
MATERIALS AND METHODS
The effect on the growth of six human retinoblastoma cell lines and a normal human fibroblast cell line of CEP1347, a small-molecule kinase inhibitor originally developed for the treatment of Parkinson's disease and therefore with a known safety profile in humans, was examined. The role of the P53 pathway in CEP1347-induced growth inhibition was also investigated.
RESULTS
CEP1347 selectively inhibited the growth of retinoblastoma cell lines expressing murine double minute 4 (MDM4), a P53 inhibitor. Furthermore, CEP1347 reduced the expression of MDM4 and activated the P53 pathway in MDM4-expressing retinoblastoma cells, which was required for the inhibition of their growth by CEP1347.
CONCLUSION
We propose CEP1347 as a promising candidate for the treatment of retinoblastomas, where functional inactivation of P53 as a result of MDM4 activation is reportedly common.
Topics: Animals; Antineoplastic Agents; Carbazoles; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Repositioning; Gene Expression Regulation, Neoplastic; Humans; Mice; Proto-Oncogene Proteins; Retinoblastoma; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 32878784
DOI: 10.21873/anticanres.14499 -
Journal of the National Cancer Institute Sep 2019Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However,...
BACKGROUND
Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood.
METHODS
Among 2053 retinoblastoma patients diagnosed during 1914-2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population.
RESULTS
Most deaths occurred in 1129 hereditary retinoblastoma patients (n = 518 deaths, cumulative mortality 70 years after retinoblastoma = 75.8%, 95% CI = 69.0% to 82.6%; SMR = 8.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR = 27.4, 95% CI = 24.2 to 30.9; AER = 72.3 deaths/10 000 person-years), for which SMRs were highest 15-29 years after diagnosis (n = 69, SMR = 89.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n = 14, SMR = 6.7, 95% CI = 3.6 to 11.2), whereas AERs increased with time (AER<15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n = 27, SMR = 1.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients.
CONCLUSION
Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past.
Topics: Age Factors; Cancer Survivors; Cause of Death; Child, Preschool; Female; History, 20th Century; History, 21st Century; Humans; Infant; Male; Population Surveillance; Prevalence; Retinoblastoma; United States
PubMed: 30698734
DOI: 10.1093/jnci/djy227 -
Cancer May 1977The occurrence of independent brain tumors in two patients with retinoblastoma is described. One patient with well-differentiated biliteral retinoblastomas developed,...
The occurrence of independent brain tumors in two patients with retinoblastoma is described. One patient with well-differentiated biliteral retinoblastomas developed, over two years later, a pineal tumor but no other metastatic lesions. The pineal tumor was composed of small neuroblastic cells and a second population of larger cells with vesicular nuclei and more abundant cytoplasm. This feature is not characteristic of either primary or metastatic retinoblastoma. In the second patient the symptoms of a brain tumor led to the discovery of a small uniocular, well-differentiated retinoblastoma. The brain tumor was retrochiasmal, highly differentiated (showing areas of photoreceptor differentiation), and interpreted as an ectopic nonmetastatic retinoblastoma. The possible histogenetic origins of the brain tumors are discussed. Patients who develop symptoms of a brain tumor after a prolonged interval since the treatment of their ocular tumors should be suspected of harboring a second intracranial primary.
Topics: Brain Neoplasms; Eye Neoplasms; Female; Humans; Hypothalamus; Infant; Male; Neoplasms, Multiple Primary; Optic Chiasm; Pineal Gland; Retinoblastoma
PubMed: 870165
DOI: 10.1002/1097-0142(197705)39:5<2048::aid-cncr2820390522>3.0.co;2-9 -
Revista de Investigacion Clinica;... 2005In order to define the molecular and cellular bases of the development of retinoblastomas it is necessary to know its etiology, and to apply the advances in genome... (Review)
Review
In order to define the molecular and cellular bases of the development of retinoblastomas it is necessary to know its etiology, and to apply the advances in genome technology to this kind of neoplasia. Retinoblastomas are childhood tumors of the eye with an average incidence of one case in every 15,000-20,000 live births, which occur in sporadic and hereditary forms. The sporadic form appears regularly as a unilateral tumor, while in the familial form of the disease, tumors may be unilateral and bilateral. This neoplasia is characterized by leukocoria, strabism, and heterochromia. The retinoblastoma gene (RB1) is a molecular marker of retinoblastoma tumors. This gene is located in chromosome 13q14.2 and encodes a nuclear phosphoprotein (pRB) of 110 KDa, which plays a major role in cell proliferation control through cell cycle-regulated phosphorylation/dephosphorylation cycles of this protein. The RB1 gene is mainly affected by point mutations, which occur most frequently in exons 3, 8, 18 and 20. At the end of the last century, DNA technology has improved notably, allowing for its application to the study of a vast array of diseases. The aim of this work is to show the molecular aspects involved in retinoblastoma which are currently deciphering; this is possible thanks to new technology platforms that have been developed. This will allow us in a near future, to offer tests for the early diagnoses, prognoses, and the determination of individual predisposition towards this neoplasia.
Topics: Cell Cycle; Cell Division; Chromosomes, Human, Pair 13; DNA Methylation; Exons; Eye Neoplasms; Gene Expression Regulation; Genes, Retinoblastoma; Genetic Techniques; Humans; Incidence; Infant, Newborn; Neoplasms, Multiple Primary; Phosphorylation; Point Mutation; Protein Processing, Post-Translational; Retinoblastoma; Retinoblastoma Protein
PubMed: 16315642
DOI: No ID Found -
Asia-Pacific Journal of Ophthalmology... 2018To investigate hand-held optical coherence tomography (HH-OCT) characteristics of small (<1 mm thickness) retinoblastoma. (Observational Study)
Observational Study
PURPOSE
To investigate hand-held optical coherence tomography (HH-OCT) characteristics of small (<1 mm thickness) retinoblastoma.
DESIGN
Retrospective observational case series.
METHODS
Patient and tumor data were extracted from the medical record and analyzed along with HH-OCT scans. Determination of tumor layer of origin was performed using a layer-by-layer analysis of HH-OCT data and specific HH-OCT-related features were described.
RESULTS
There were 20 sub-millimeter retinoblastomas from 16 eyes of 15 patients. Mean largest tumor basal diameter by HH-OCT was 2.2 mm (median, 1.9; range, 0.7-4.1 mm), and mean tumor thickness was 468 μm (median, 441; range, 151-998 μm). In all cases, the retinoblastoma caused discontinuity or disruption of the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), and external limiting membrane (ELM) layers (20/20, 100%). Tumor origin was in the INL in 19/20 (95%) and equivocal (INL vs ONL) in 1/20 (5%). Intratumoral microcalcification was present in 14/20 tumors (70%). There were 2 characteristic findings (signs) on HH-OCT including the INL "fish tail" sign with splaying of the INL at the tumor margin (19/20, 95%) and the ONL "shark fin" sign with folding of the ONL and OPL, conforming to the lateral tumor margins (15/20, 75%). Both signs were concurrently present in 15 tumors (15/20, 75%).
CONCLUSIONS
HH-OCT demonstrated that sub-millimeter retinoblastoma seems to originate from the INL, with tumor base and thickness growth progressing in a linear relationship. Characteristic HH-OCT findings included intratumoral microcalcification, INL "fish tail" sign, and ONL "shark fin" sign.
Topics: Female; Humans; Infant; Male; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Tomography, Optical Coherence
PubMed: 29984562
DOI: 10.22608/APO.2018189 -
Journal of the Indian Medical... Aug 2003It is important that retinoblastoma is considered as a possible diagnosis in all children presenting with a white reflex in the pupil. A constant unilateral strabismus... (Review)
Review
It is important that retinoblastoma is considered as a possible diagnosis in all children presenting with a white reflex in the pupil. A constant unilateral strabismus with poor visual acuity is the next common method of presentation. Heritable tumours are more likely to be bilateral and occur earlier. Unilateral retinoblastomas present on an average at 24 months of age while bilateral disease at 12 months. The management of retinoblastoma had been revolutionised over the last decade. The introduction of gene testing in relatives with a known germ-line mutation has simplified follow-up. The early detection of small and medium sized tumours has lent itself to focal treatment with laser therapy. Chemoreduction followed by focal laser or cryotherapy can salvage eyes with large tumours. Thermotherapy reduces the amount of scarring associated with other modalities of focal treatment. Radiation in the form of brachytherapy or teletherapy is largely limited to tumours resistant to other forms of treatment due to the risk of local complications and the higher risk of secondary cancers in the field of radiation.
Topics: Child, Preschool; Diagnosis, Differential; Humans; Infant; Retinal Neoplasms; Retinoblastoma
PubMed: 15071798
DOI: No ID Found