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Pediatric Blood & Cancer Sep 2023The Children's Oncology Group (COG) Rare Tumor Committee includes the Infrequent Tumor and Retinoblastoma subcommittees, encompassing a wide range of extracranial solid...
The Children's Oncology Group (COG) Rare Tumor Committee includes the Infrequent Tumor and Retinoblastoma subcommittees, encompassing a wide range of extracranial solid tumors that do not fall within another COG disease committee. Current therapeutic trial development focuses on nasopharyngeal carcinoma, adrenocortical carcinoma, pleuropulmonary blastoma, colorectal carcinoma, melanoma, and thyroid carcinoma. Given the rarity of these tumors, novel strategies and international collaborative efforts are necessary to advance research and improve outcomes.
Topics: Child; Humans; Medical Oncology; Thyroid Neoplasms; Adrenal Cortex Neoplasms; Nasopharyngeal Neoplasms; Retinal Neoplasms
PubMed: 37458616
DOI: 10.1002/pbc.30574 -
Journal of Pediatric Ophthalmology and... 2024
Topics: Humans; Retinoblastoma; Penetrance; Retinal Neoplasms; Pedigree; Mutation
PubMed: 37489625
DOI: 10.3928/01913913-20230427-03 -
Asia-Pacific Journal of Ophthalmology... 2024Masquerade syndromes in uveitis are complex clinical conditions where non-inflammatory diseases mimic uveitic manifestations, often leading to diagnostic and therapeutic... (Review)
Review
Masquerade syndromes in uveitis are complex clinical conditions where non-inflammatory diseases mimic uveitic manifestations, often leading to diagnostic and therapeutic challenges. This review delves into the diverse spectrum of masquerade syndromes, categorizing them into neoplastic and non-neoplastic entities. We explore the prevalence of primary intraocular lymphoma, leukaemia, retinoblastoma, and other malignancies, as well as conditions like retinitis pigmentosa and endophthalmitis that can present as uveitis. Through detailed analysis of symptoms, diagnostic methods, and treatment approaches, the review emphasizes the importance of considering masquerade syndromes in differential diagnoses to prevent mismanagement. The synthesis of current knowledge aims to enhance clinicians' ability to discern these complex presentations, advocating for a multidisciplinary approach to diagnosis and care, thereby improving patient outcomes in cases of uveitic masquerade syndromes.
Topics: Humans; Uveitis; Diagnosis, Differential
PubMed: 38583526
DOI: 10.1016/j.apjo.2024.100054 -
EJC Paediatric Oncology Dec 2023Retinoblastoma is rare but nevertheless the most common pediatric eye cancer that occurs in children under age 5. High-resolution metabolomics (HRM) is a powerful...
BACKGROUND
Retinoblastoma is rare but nevertheless the most common pediatric eye cancer that occurs in children under age 5. High-resolution metabolomics (HRM) is a powerful analytical approach to profile metabolic features and pathways or identify metabolite biomarkers. To date, no studies have used pre-diagnosis blood samples from retinoblastoma cases and compared them to healthy controls to elucidate early perturbations in tumor pathways.
OBJECTIVES
Here, we report on metabolic profiles of neonatal blood comparing cases later in childhood diagnosed with retinoblastoma and controls.
METHODS
We employed untargeted metabolomics analysis using neonatal dried blood spots for 1327 children (474 retinoblastoma cases and 853 healthy controls) born in California from 1983 to 2011. Cases were selected from the California Cancer Registry and controls, frequency matched to cases by birth year, from California birth rolls. We performed high-resolution metabolomics to extract metabolic features, partial least squares discriminant analysis (PLS-DA) and logistic regression to identify features associated with disease, and Mummichog pathway analysis to characterize enriched biological pathways.
RESULTS
PLS-DA identified 1917 discriminative features associated with retinoblastoma and Mummichog identified 14 retinoblastoma-related enriched pathways including linoleate metabolism, pentose phosphate pathway, pyrimidine metabolism, fructose and mannose metabolism, vitamin A metabolism, as well as fatty acid and lipid metabolism.
INTERPRETATION
Our findings linked a retinoblastoma diagnosis in early life to newborn blood metabolome perturbations indicating alterations in inflammatory pathways and energy metabolism. Neonatal blood spots may provide a venue for early detection for this or potentially other childhood cancers.
PubMed: 38130370
DOI: 10.1016/j.ejcped.2023.100123 -
Canadian Journal of Ophthalmology.... Feb 2024Since the introduction of intraarterial chemotherapy (IAC) in the last decade, there has been a paradigm shift in the management of retinoblastoma (RB), especially in... (Review)
Review
Since the introduction of intraarterial chemotherapy (IAC) in the last decade, there has been a paradigm shift in the management of retinoblastoma (RB), especially in developed countries. Despite improved globe salvage outcomes with IAC compared with systemic intravenous chemotherapy, IAC has certain limitations, such as poor accessibility and affordability, especially for middle- and low-income countries; the need for expertise; local ocular complications; and possible increased risk of systemic metastasis. This review discusses the important limitations of the current treatment strategy of using IAC, as well as the prospects of new therapeutic targets or routes of drug delivery that may lead to further improvements in the management of RB.
PubMed: 38431272
DOI: 10.1016/j.jcjo.2024.01.013 -
Ophthalmic Epidemiology Oct 2023To determine the seasonal variation in the diagnosis of retinoblastoma in a global sample of children and to investigate predictors of seasonal trends.
PURPOSE
To determine the seasonal variation in the diagnosis of retinoblastoma in a global sample of children and to investigate predictors of seasonal trends.
METHODS
Data were collected through a global, multicenter, 1-year cross-sectional analysis that included all treatment- naïve retinoblastoma patients presenting to participating centers between January 1, 2017, and December 31, 2017. Due to variations in days per month, data were normalized to a 30-day/month calendar. Observed data were compared to a simulation study of expected results using a uniform distribution.
RESULTS
Patient-level data were available for 4,351 children from 276 centers in 153 countries, of which 3,966 had a month of presentation recorded. There were relative peaks in disease presentation in January and July, with lower counts in November and December (p = .0015). No covariates were found to be significantly associated with the seasonal trend. Two covariates, patient age at presentation and extraocular tumor spread, showed a moderate association with month of presentation.
CONCLUSION
Our findings suggest seasonal trends in the presentation of retinoblastoma across the world. However, these trends do not appear to be related to income level of a country, climate, or other covariates. Any connection between seasonal variation of retinoblastoma presentation and retinoblastoma outcomes remains unclear or not present.
Topics: Child; Humans; Seasons; Retinoblastoma; Cross-Sectional Studies; Retinal Neoplasms
PubMed: 36503408
DOI: 10.1080/09286586.2022.2153872 -
Cancer Gene Therapy Aug 2023Colorectal cancer (CRC) poses one of the most serious threats to human health worldwide, and abnormally expressed c-Myc and p53 are deemed the pivotal driving forces of...
Colorectal cancer (CRC) poses one of the most serious threats to human health worldwide, and abnormally expressed c-Myc and p53 are deemed the pivotal driving forces of CRC progression. In this study, we discovered that the lncRNA FIT, which was downregulated in CRC clinical samples, was transcriptionally suppressed by c-Myc in vitro and promoted CRC cell apoptosis by inducing FAS expression. FAS is a p53 target gene, and we found that FIT formed a trimer with RBBP7 and p53 that facilitated p53 acetylation and p53-mediated FAS gene transcription. Moreover, FIT was capable of retarding CRC growth in a mouse xenograft model, and FIT expression was positively correlated with FAS expression in clinical samples. Thus, our study elucidates the role of the lncRNA FIT in human colorectal cancer growth and provides a potential target for anti-CRC drugs.
Topics: Humans; Animals; Mice; Tumor Suppressor Protein p53; Acetylation; RNA, Long Noncoding; Cell Proliferation; Colorectal Neoplasms; Carcinogenesis; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Retinoblastoma-Binding Protein 7
PubMed: 37225855
DOI: 10.1038/s41417-023-00624-z -
Cell Reports Aug 2023Cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (RB) are both important cell-cycle regulators that function in different scenarios. Here, we report that FERM...
Cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (RB) are both important cell-cycle regulators that function in different scenarios. Here, we report that FERM domain-containing 8 (FRMD8) inhibits CDK4 activation and stabilizes RB, thereby causing cell-cycle arrest and inhibiting colorectal cancer (CRC) cell growth. FRMD8 interacts separately with CDK7 and CDK4, and it disrupts the interaction of CDK7 with CDK4, subsequently inhibiting CDK4 activation. FRMD8 competes with MDM2 to bind RB and attenuates MDM2-mediated RB degradation. Frmd8 deficiency in mice accelerates azoxymethane/dextran-sodium-sulfate-induced colorectal adenoma formation. The FRMD8 promoter is hypermethylated, and low expression of FRMD8 predicts poor prognosis in CRC patients. Further, we identify an LKCHE-containing FRMD8 peptide that blocks MDM2 binding to RB and stabilizes RB. Combined application of the CDK4 inhibitor and FRMD8 peptide leads to marked suppression of CRC cell growth. Therefore, using an LKCHE-containing peptide to interfere with the MDM2-RB interaction may have therapeutic value in CDK4/6 inhibitor-resistant patients.
Topics: Animals; Mice; Colonic Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Phosphorylation; Retinoblastoma Protein
PubMed: 37527040
DOI: 10.1016/j.celrep.2023.112886 -
Ophthalmology Apr 2024To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia.
PURPOSE
To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia.
DESIGN
Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter.
PARTICIPANTS
A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries.
INTERVENTIONS
Chemotherapy, radiotherapy, enucleation, and orbital exenteration.
MAIN OUTCOME MEASURES
Enucleation and death.
RESULTS
Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively.
CONCLUSIONS
At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia.
FINANCIAL DISCLOSURE(S)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Topics: Child; Humans; Male; Female; Infant; Child, Preschool; Retinoblastoma; Retinal Neoplasms; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Asia; Retrospective Studies; Eye Enucleation
PubMed: 37839559
DOI: 10.1016/j.ophtha.2023.10.015