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1.
Niger J Clin Pract ; 23(5): 654-659, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32367872

RESUMO

Background: Tumours of the eye and adnexa demonstrate great histologic variety and constitute a serious threat to vision especially in children. Aims: The study aims to review the epidemiologic and pathologic characteristics of tumours of the eye and ocular adnexa in the paediatric age group (0-14 years). Methods: All the cases entered into the departmental records as tumours of the eye and ocular adnexa over a 10-year period in the age group 0-14 years were extracted. The patients' request cards with all relevant Haematoxylin & Eosin (H & E)-stained histology slides were retrieved. All the slides were reviewed and the cases were classified in accordance with the 4th edition of the WHO Classification of Tumours of the Eye (2018). The collected data were subjected to descriptive statistical tabulation and analysis. Results: A total of 104 tumours of the eye and ocular adnexae were diagnosed in the paediatric age group, accounting for 40.5% of all eye and ocular adnexal tumours diagnosed over the study period. The male to female ratio was 1.7:1 and malignant tumours greatly outnumbered benign tumours by a ratio of 5.5:1. Majority (76%) of the tumours occurred in the retina with retinoblastoma representing all the tumours diagnosed in this location. Rhabdomyosarcoma was the most common paediatric orbital tumour accounting for over half (53.8%) of all tumours in the orbit. Tumours of the conjunctiva and the eyelid were infrequent with benign soft tissue tumours (vascular, neural and lipomatous tumours) being the major tumours at these sites. Conclusion: Retinoblastoma is the single most common tumour in this age group.


Assuntos
Doenças dos Anexos/patologia , Neoplasias Oculares/patologia , Neoplasias Orbitárias/patologia , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Adenoma , Doenças dos Anexos/epidemiologia , Adolescente , Criança , Pré-Escolar , Neoplasias Oculares/epidemiologia , Feminino , Humanos , Lactente , Masculino , Nigéria/epidemiologia , Neoplasias Orbitárias/epidemiologia , Neoplasias da Retina/epidemiologia , Retinoblastoma/epidemiologia , Estudos Retrospectivos , Centros de Atenção Terciária
2.
PLoS One ; 15(4): e0231394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287312

RESUMO

miRNAs regulate post-transcriptional gene expression in metazoans, and thus are involved in many fundamental cellular biological processes. Extracellular miRNAs are also found in most human biofluids including plasma. These circulating miRNAs constitute a long distance inter cellular communication system and are potentially useful biomarkers. High throughput technologies like microarrays are able to scan a complete miRNome providing useful detection scores that are underexplored. We proposed to answer how many and which miRNAs are detectable in plasma or extracellular vesicles as these questions have not yet been answered. We set out to address this knowledge gap by analyzing the mirRNome in plasma and corresponding extracellular vesicles (EVs) from 12 children affected by retinoblastoma (Rb) a childhood intraocular malignant tumor, as well as from 12 healthy similarly aged controls. We calculated an average of 537 detectable miRNAs in plasma and 625 in EVs. The most miRNA enriched compartment were EVs from Rb cases with an average of 656 detectable elements. Using hierarchical clustering with the detection scores, we generated broad detection mirnome maps and identified a plasma signature of 19 miRNAs present in all Rb cases that is able to discriminate cases from controls. An additional 9 miRNAs were detected in all the samples; within this group, miRNA-5787 and miRNA-6732-5p were highly abundant and displayed very low variance across all the samples, suggesting both are good candidates to serve as plasma references or normalizers. Further exploration considering participant's sex, allowed discovering 5 miRNAs which corresponded only to females and 4 miRNAs corresponding only to males. Target and pathway analysis of these miRNAs revealed hormonal function including estrogen, thyroid signaling pathways and testosterone biosynthesis. This approach allows a comprehensive unbiased survey of a circulating miRNome landscape, creating the possibility to define normality in mirnomic profiles, and to locate where in these miRNome profiles promising and potentially useful circulating miRNA signatures can be found.


Assuntos
Vesículas Extracelulares/metabolismo , MicroRNAs/sangue , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Pré-Escolar , MicroRNA Circulante/sangue , Análise por Conglomerados , Análise Discriminante , Feminino , Humanos , Lactente , Masculino , MicroRNAs/análise , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Retina/genética , Retinoblastoma/genética
4.
Invest Ophthalmol Vis Sci ; 61(3): 32, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32186675

RESUMO

Purpose: The pivotal role of microRNAs (miRNAs or miRs) has been proved in the pathogenesis of retinoblastoma. miR-224-3p is demonstrated to be involved in several tumors. However, the underlying mechanism of miR-224-3p in retinoblastoma is yet to be investigated. Therefore, this study was designed to identify the regulation of miR-224-3p in human retinoblastoma. Methods: The expression pattern of miR-224-3p and large tumor suppressor 2 (LATS2) in retinoblastoma was measured by reverse transcription quantitative polymerase chain reaction. Afterward, the interaction between miR-224-3p and LATS2 was identified using a dual luciferase reporter gene assay. Next, gain-of-function and loss-of-function approaches were employed to examine the effects of miR-224-3p and LATS2 as well as their interaction on cell apoptosis, proliferation and angiogenesis abilities, and tumorigenesis. Whether the Hippo-YAP signaling pathway was involved in tumorigenesis was analyzed by determining downstream genes. Results: LATS2 was downregulated in retinoblastoma, and its overexpression promoted apoptosis and suppressed proliferation of retinoblastoma cells. miR-224-3p, highly expressed in retinoblastoma, inhibited the expression of its target gene LATS2, which inhibited activation of the Hippo-YAP signaling pathway. Suppression of miR-224-3p promoted apoptosis while suppressing the proliferation of retinoblastoma cells and angiogenesis. Tumor progression induced by upregulation of miR-224-3p was diminished by restoration of LATS2. It was observed that tumor growth and angiogenesis were reduced by depleted miR-224-3p in the animal experiments. Conclusions: The present study suggests that miR-224-3p targets LATS2 and blocks the Hippo-YAP signaling pathway activation, thus preventing the progression of retinoblastoma, which could be a new therapeutic target for retinoblastoma.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Neoplasias da Retina/genética , Retinoblastoma/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Animais , Apoptose , Western Blotting , Criança , Pré-Escolar , Progressão da Doença , Regulação para Baixo , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Retina/irrigação sanguínea , Neoplasias da Retina/patologia , Neovascularização Retiniana/metabolismo , Retinoblastoma/irrigação sanguínea , Retinoblastoma/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Transfecção , Células Tumorais Cultivadas
5.
Cancer Sci ; 111(4): 1417-1421, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32056332

RESUMO

The characteristics of tumor cells of primary vitreoretinal lymphoma (PVRL) have not been defined, although researches have shown that most cases are of diffuse large B-cell lymphoma (DLBCL). To determine the subtype and biological characteristics of tumor cells of PVRL, we performed a gene expression profiling analysis. RNA was extracted from the vitreous fluid of 7 PVRL patients and from nodal samples of 10 DLBCL patients: 6 of germinal center B-cell (GCB) type and 4 of activated B-cell (ABC) type determined by Hans' criteria. Six PVRL samples showed gene expression profiles that were similar to each other. The patterns were different from those of the ABC-type nodular DLBCL but relatively close to those of the GCB-type nodular DLBCL. Interestingly, all of the 6 examined PVRL samples had either MYD88L265P or mutation in the immunoreceptor tyrosine-based activation motif (ITAM) region of CD79B. Five PVRL patients with similar gene expression profiles were treated with a standardized regimen: intravitreal administration of methotrexate (MTX) followed by six courses of systemic high doses of MTX. As a result, 2 patients had CD79B mutations and showed early central nervous system (CNS) progression. Patients without CNS progression did not have this mutation. In conclusion, PVRL had unique genetic features: an expression pattern different from ABC-type and relatively close to GCB-type DLBCL. CD79B mutations showed potential to serve as prognostic markers for CNS progression.


Assuntos
Antígenos CD79/genética , Linfoma Difuso de Grandes Células B/genética , Neoplasias da Retina/genética , Corpo Vítreo/metabolismo , Idoso , Linfócitos B/patologia , Biomarcadores Tumorais/genética , Sistema Nervoso Central/patologia , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Análise em Microsséries , Mutação , Neoplasias da Retina/patologia , Corpo Vítreo/patologia
6.
Pediatr Blood Cancer ; 67(4): e28158, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31904159

RESUMO

BACKGROUND: The long-term survival of germline retinoblastoma patients is decreased due to the risk of second primary tumors (SPTs) that occur years after the diagnosis of retinoblastoma. This risk is related to genetic predisposition and other factors, such as the treatment of retinoblastoma by external beam radiotherapy (EBRT). PROCEDURE: We studied the incidence, risk factors, and prognosis of specific craniofacial SPTs developed within the margins of radiation field in a cohort of 209 patients with germline retinoblastoma treated with EBRT at our institution between 1977 and 2010. Clinical characteristics, survival, incidence, and histology of craniofacial SPTs were recorded. RESULTS: Fifty-three of the 209 patients developed 60 distinct craniofacial SPTs in irradiated field with a median time from EBRT of 16.9 years (4-35) and a median follow-up of 24.8 years (5.3-40). Osteosarcoma (33.3%) and undifferentiated sarcoma (23.3%) were the more prevalent histological entities. Benign tumors (16.7%) also occurred. The cumulative incidence of craniofacial SPTs reached 32.6% at 35 years after EBRT, and the median survival after diagnosis was five years. In our series, irradiation under 12 months of age, bilateral EBRT, or previous treatment of retinoblastoma with chemotherapy did not significantly increase the risk of craniofacial SPTs. CONCLUSIONS: This work presents a strong argument to avoid EBRT in the management of retinoblastoma and emphasizes the high risk and poor prognosis of specific craniofacial SPTs. This study also points to the question of the need and benefits of special programs for early detection of craniofacial SPTs in survivors of irradiated germline retinoblastoma.


Assuntos
Predisposição Genética para Doença , Células Germinativas/patologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia/efeitos adversos , Neoplasias da Retina/radioterapia , Retinoblastoma/radioterapia , Adolescente , Adulto , Sobreviventes de Câncer/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/patologia , Prognóstico , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Retinoblastoma/genética , Retinoblastoma/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
7.
BMC Ophthalmol ; 20(1): 10, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906917

RESUMO

BACKGROUND: Developing objective and repeatable indicators to evaluate the efficacy of PVRL treatment is important. The quantification of vitreous cells is a traditional criterion; however slight changes are difficult to ascertain. Spectral domain optical coherence tomography (SD-OCT) is objective, repeatable, and easily explained. The purpose of this study is to provide a longitudinal observation of OCT in PVRL treated with intravitreal injections of methotrexate (MTX) and to evaluate the utility of OCT in monitoring responsiveness of PVRL to treatment. METHODS: The medical records of patients with biopsy-positive PVRL attending our hospital between January 2016 and September 2017 who received intravitreal injections of MTX were included in this study. Pre- and post-treatment OCT images were reviewed independently by two researchers. RESULTS: Of the 24 cases reviewed, 10 patients (18 eyes) were included. SD-OCT abnormalities at the initial visit included vitreous cells (18/18), OR (outer retina) fuzzy borders (12/18), PED (pigment epithelium detachments) (9/18), subretinal hyperreflective infiltration (3/18), intraretinal infiltration (8/18), and SRF (subretinal fluid) (4/18). Post induction treatment, SRF in cases with RD (retinal detachment) was absorbed, and subretinal fibrosis appeared. Other lesions were significantly reduced. Post consolidation treatment, OR fuzzy borders, PED and SRF disappeared in 2 eyes, intraretinal infiltration disappeared in 1 eye, and other abnormalities further improved. Additionally, retinal fibrosis was observed in 3 eyes. One month post maintenance treatment, all abnormalities observed at the first visit vanished. At the last visit, OCT showed subretinal fibrosis and in 3 eyes (16.7%), the disruption of outer retina in 9 eyes (50%) and thinning of the whole layer in 4 eyes (22.2%). CONCLUSIONS: Our observations reveal that characteristic OCT features in PVRL patients can reduce gradually and finally vanish with therapy. We propose that SD-OCT may be employed to monitor the responsiveness of PVRL to treatment, which may influence decision making in the management of this disease.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Linfoma , Metotrexato/administração & dosagem , Neoplasias da Retina , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Feminino , Humanos , Injeções Intravítreas , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/patologia , Corpo Vítreo/patologia
8.
Pediatr Blood Cancer ; 67(3): e28101, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793213

RESUMO

BACKGROUND: Cytomegalovirus (CMV) disease is underrecognized in children with retinoblastoma. This study investigated rates of CMV infection and disease in this specific population receiving chemotherapy. METHODS: From a cohort of 164 patients with retinoblastoma diagnosed from 2011 to 2018, 107 patients were evaluated for CMV infection determined by antigenemia assay or real-time PCR. Preemptive CMV screening was implemented in 2013. CMV disease was diagnosed by tissue biopsy, culture, or ophthalmic examination. RESULTS: Thirty-seven and 70 patients before and after the screening strategy, respectively, were included. Before screening, 10/37 (27%) were diagnosed with CMV infection during chemotherapy. Among them, 5 (50%) developed CMV disease (hepatitis, pneumonia, and retinitis) and one patient died of CMV pneumonia. During screening, 18/70 (26%) were documented with 36 episodes of CMV infection and 9 patients received 25 preemptive antiviral therapies. Age at chemotherapy tended to be younger in patients with CMV infection, and fewer were seronegative prior to chemotherapy. Patients who started chemotherapy at <12 months of age received preemptive therapies significantly more often than those started at ≥12 months. Two (11%) out of 18 patients with CMV infection developed CMV retinitis and colitis, and there were no fatal cases. Preemptive therapy along with active CMV screening significantly reduced the risk of developing CMV disease, from 14% to 2.9% (P = 0.047). CONCLUSIONS: Children with retinoblastoma can experience significant morbidity and even mortality from CMV infection during chemotherapy in Korea. Preemptive screening and appropriate antiviral therapy can reduce the development of CMV disease and subsequent mortality.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Programas de Rastreamento/estatística & dados numéricos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antivirais/uso terapêutico , Pré-Escolar , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , República da Coreia/epidemiologia , Neoplasias da Retina/patologia , Neoplasias da Retina/virologia , Retinoblastoma/patologia , Retinoblastoma/virologia , Estudos Retrospectivos
9.
Histochem Cell Biol ; 153(2): 101-109, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31781967

RESUMO

Retinoblastoma (RB) is a childhood eye tumor, caused by the RB1 gene mutation. Since RB is a rapidly proliferating tumor, the patient presents with a Group-D/E tumor at the time of diagnosis. Enucleation is preferred in most unilateral cases to prevent metastasis. Various cell lines have been established to study the tumor's growth pattern and target the cancer cells. The commonly used cell lines are WERI-Rb-1 and Y79, both isolated from the primary tumor of RB. Cell lines established from the metastatic site of RB have not been characterized before. In this study, we have characterized NCC-RbC-51, derived from RB tumor to cervical lymph node site and investigated its potential to represent a highly aggressive and metastatic tumor. We compared the proliferative and invasive properties of NCC-RbC-51 with a cell line isolated from the primary site, WERI-Rb-1. NCC-RbC-51 had higher rates of proliferation and apoptosis and had better invasive ability. Copy number variation analysis and the pathways predicted from these show that the pathways altered in NCC-RbC-51 could contribute to its metastatic nature. In all, the results suggest that NCC-RbC-51, a cell line isolated from metastatic site, could be a potential model to study aggressive/invasive RB.


Assuntos
Neoplasias da Retina/patologia , Retinoblastoma/patologia , Proliferação de Células , Variações do Número de Cópias de DNA/genética , DNA de Neoplasias/genética , Humanos , Mutação , Fotomicrografia , Neoplasias da Retina/genética , Neoplasias da Retina/secundário , Retinoblastoma/genética , Retinoblastoma/secundário , Proteínas de Ligação a Retinoblastoma/genética , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/genética
10.
Pediatr Blood Cancer ; 67(1): e27998, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571399

RESUMO

BACKGROUND: Retinoblastoma with macroscopic optic nerve (ON) invasion depicted by imaging at diagnosis remains a major problem and carries a poor prognosis. We sought to describe the treatment and outcome of these high-risk patients. METHODS: Retrospective mono-institutional clinical, radiological, and histological review of patients with uni- or bilateral retinoblastoma with obvious ON invasion, defined by radiological optic nerve enlargement (RONE) depicted by computed tomography scan or magnetic resonance imaging (MRI), was performed. RESULTS: Between 1997 and 2014, among the 936 patients with retinoblastoma treated at Institut Curie, 11 had detectable RONE. Retinoblastoma was unilateral in 10 and bilateral in one. Median age at diagnosis was 28 months (range, 11-96). ON enlargement extended to the orbital portion in three patients, to the optic canal in five, to the prechiasmatic portion in two, and to the optic chiasm in one. Nine patients received neoadjuvant chemotherapy and partial response was obtained in all. Enucleation was performed in 10/11 patients-by an anterior approach in three and by anterior and subfrontal approaches in seven. Three patients had a positive ON resection margin (2/3 after primary enucleation). All enucleated patients received adjuvant treatment (conventional chemotherapy: 10, high-dose chemotherapy: seven, radiotherapy: five). Leptomeningeal progression occurred in four patients. Seven are in first complete remission (median follow up: 8 years [3.5-19.4]). CONCLUSION: Neoadjuvant chemotherapy and microscopic complete resection have a pivotal role in the management of retinoblastoma with RONE. MRI is recommended for initial and pre-operative accurate staging. Surgery should be performed by neurosurgeons in case of posterior nerve invasion. Radiotherapy is required in case of incomplete resection.


Assuntos
Neoplasias do Nervo Óptico/patologia , Nervo Óptico/patologia , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Invasividade Neoplásica , Neoplasias do Nervo Óptico/diagnóstico por imagem , Neoplasias do Nervo Óptico/terapia , Prognóstico , Neoplasias da Retina/diagnóstico por imagem , Neoplasias da Retina/terapia , Retinoblastoma/diagnóstico por imagem , Retinoblastoma/terapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
11.
Pathol Res Pract ; 215(12): 152641, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31727502

RESUMO

BACKGROUND: Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Accumulating evidences have clarified that microRNAs (miRNAs) modulated signaling molecules by acting as oncogenes or tumor-suppressor genes in RB. Thus, in our study, we aimed to investigate the function of miR-129-5p in RB cells through PI3K/AKT signaling pathway by targeting PAX6. Two RB cell lines, Y79 and WERI-Rb-1, were selected in our study, followed by transfection of miR-129-5p inhibitor or si-PAX6 to explore the regulatory role of miR-129-5p in RB cell proliferation, invasion and migration. MATERIAL AND METHODS: Dual-luciferase assay was used for the detection of targeting relationship between miR-129-5p and PAX6. Besides, western blot analysis was applied to detect expression of cell cycle-related factors (CDK2 and Cyclin E) and PI3K/AKT signaling pathway-related factors (p-AKT and AKT). Nude mice tumorigenesis experiment was used to evaluate the effect of miR-129a-5p on RB growth in vivo. RESULTS: miR-129-5p was down-regulated in RB cell lines. miR-129-5p directly targeted the 3'-untranslated region of PAX6. Artificial down-regulation of miR-129-5p promoted cell proliferation, migration and invasion in RB cell lines Y79 and WERI-Rb-1, and promoted RB growth in vivo via PI3K/AKT signaling pathway, which could be reversed by transfection with silencing PAX6. CONCLUSION: This study provides evidences that RB progression was suppressed by overexpressed miR-129-5p via direct targeting of PAX6 through PI3K/AKT signaling pathway, which may provide a molecular basis for better treatment for RB.


Assuntos
Movimento Celular , Proliferação de Células , MicroRNAs/metabolismo , Fator de Transcrição PAX6/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias da Retina/enzimologia , Retinoblastoma/enzimologia , Animais , Ciclo Celular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Fator de Transcrição PAX6/genética , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Retinoblastoma/genética , Retinoblastoma/patologia , Transdução de Sinais , Carga Tumoral
12.
Zhonghua Yan Ke Za Zhi ; 55(11): 854-859, 2019 Nov 11.
Artigo em Chinês | MEDLINE | ID: mdl-31715683

RESUMO

Objective: To analyze the histopathological features and histopathological risk factors (HRF) of tumor recurrence after vitrectomy in patients with retinoblastoma (RB). Methods: Retrospective case series. Twenty-nine patients (29 eyes) who underwent enucleation from April 2014 to April 2019 at the Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University due to tumor recurrence after vitrectomy in the other hospitals were enrolled and archived. The pathological sections of the other hospitals were read by the pathologists of the department and the pathological report was written. Histopathological features and HRF were analyzed in this group of patients. The HRF used in this study was defined as tumor invasion of the optic nerve, the choroid (the largest diameter ≥ 3 mm and mostly reaching the inner sclera), the sclera, the anterior segment of the eye, and tumor passing through the scleral and growing outside the eyeball. Results: Of the 29 patients with RB recurrence after vitrectomy, 18 (62.1%) were male and 11 (37.9%) were female. The age was 1-10 years with a median age of 3 years. Among 29 eyes, the tumor invaded the ciliary body in 19 eyes (65.5%), the iris in 14 eyes (48.3%), the anterior chamber in 10 eyes (34.5%), and the anterior chamber angle in 7 eyes (24.1%). Of the 29 eyes, 27 eyes (93.1%) had HRF. The most common HRF was invading the anterior segment of the eye(77.8%, 21/27). Conclusions: In patients with recurrence after vitrectomy for RB, the most common tumor invasion site in histopathology is the anterior segment of the eye, particularly the ciliary body. More than 90% of the patients have HRF. Vitrectomy for RB treatment requires a rigorous surgical indication assessment. (Chin J Ophthalmol, 2019, 55: 854-859).


Assuntos
Neoplasias da Retina/cirurgia , Retinoblastoma/cirurgia , Vitrectomia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Estudos Retrospectivos
13.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): e320-e323, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755984

RESUMO

Optical coherence tomography angiography (OCTA) is a novel imaging modality, and its role in the clinical evaluation of patients remains to be defined. In this report, the authors describe a case of a retinal cavernous hemangioma and show that OCTA of the lesion recapitulates many structural features first described in previous histopathologic studies, including aneurysmal architecture, septated blood flow, and epiretinal membrane. Thus, OCTA provides a new, noninvasive means of studying retinal cavernous hemangioma structure, a unique capability that may also be clinically relevant to the evaluation of other pathologic retinal vascular tumors, such as capillary and racemose hemangiomas. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e320-e323.].


Assuntos
Angiofluoresceinografia , Hemangioma Cavernoso/patologia , Neoplasias da Retina/patologia , Tomografia de Coerência Óptica , Adulto , Membrana Epirretiniana/patologia , Angiofluoresceinografia/métodos , Hemangioma Cavernoso/diagnóstico por imagem , Humanos , Masculino , Neoplasias da Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos
16.
Oncol Rep ; 42(3): 1214-1224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322174

RESUMO

Tetramethylpyrazine (TMP; an extract of the Chinese herbal medicine, Chuanxiong) has been shown to exert remarkable antiretinoblastoma (RB) effects. Based on our previous study, the target gene was found to be C­X­C chemokine receptor type 4 (CXCR4). CXCR4 is a prognostic marker in various types of cancer, but the exact mechanisms underlying the regulation of CXCR4 expression by TMP in WERI­Rb1 cells have yet to be fully elucidated. In the present study, it was revealed that TMP significantly downregulated CXCR4 expression and inhibited CXCR4 promoter activity in WERI­Rb1 cells, indicating that TMP inhibits CXCR4 expression in WERI­Rb1 cells through transcriptional regulatory mechanisms. Among the numerous transcription factors involved in CXCR4 function, including Yin Yang 1 (YY1), nuclear respiratory factor­1 (Nrf­1), Krüppel­like Factor 2 (KLF2), specificity protein 1 (SP1), and nuclear factor­κB subunit 1 (NF­κB1), only TMP led to a significant downregulation of Nrf­1 expression. Chromatin immunoprecipitation assays further indicated that Nrf­1 directly binds to the promoter region of CXCR4, and silencing Nrf­1 via siRNA transfection notably inhibited CXCR4 expression in WERI­Rb1 cells. In addition, the expression levels of both Nrf­1 and CXCR4 increased concomitantly with WERI­Rb1 cell density. Furthermore, the downregulation of Nrf­1 and CXCR4 expression in RB by TMP was confirmed in vivo. Taken together, the results of the present study have uncovered a novel mechanism in which CXCR4 expression is regulated by Nrf­1 in WERI­Rb1 cells, thereby identifying novel potential targets for the treatment of RB, and providing evidence for the clinical application of TMP in adjuvant retinoblastoma therapy.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator 1 Nuclear Respiratório/metabolismo , Pirazinas/farmacologia , Receptores CXCR4/genética , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Transcrição Genética/efeitos dos fármacos , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Nus , Fator 1 Nuclear Respiratório/genética , Receptores CXCR4/metabolismo , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/genética , Retinoblastoma/tratamento farmacológico , Retinoblastoma/genética , Células Tumorais Cultivadas , Vasodilatadores/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Biomed Pharmacother ; 118: 109111, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31336343

RESUMO

Aberrant expression of microRNAs plays an important role in the pathogenesis and progression of retinoblastoma. MiR-25, a member of the miR-106b˜25 cluster, has been reported to be abnormally expressed in retinoblastoma, but the exact role of it remains unclear. In our study, we found that miR-25-3p was upregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-25-3p in retinoblastoma cell line WERI-RB-1 increased cell growth, colony formation, anchorage-independent growth, cell migration and invasion in vitro and tumor xenograft growth in vivo. In contrast, inhibited miR-25-3p expression in retinoblastoma cell line Y79 suppressed cell growth, colony formation, anchorage-independent growth, cell migration and invasion. Through luciferase reporter assay, we found that phosphatase and tensin homolog (PTEN) was a direct target of miR-25-3p. This was verified by western blot that miR-25-3p overexpression suppressed PTEN and activated Akt signaling. In addition, miR-25-3p was found to promote epithelial-mesenchymal transition (EMT) of WERI-RB-1 cells through PTEN/Akt pathway. Western blot analysis revealed that miR-25-3p overexpression increased Vimentin and Snail expression, and suppressed E-cadherin expression, but this could be reversed by restoring PTEN. Moreover, LY294002 treatment or restoring PTEN expression abolished the effects of miR-25-3p on cell invasion, colony formation and anchorage-independent growth in vitro and tumor xenograft growth in vivo. Taken together, our results suggested that miR-25-3p promotes malignant transformation of retinoblastoma cells by suppressing PTEN.


Assuntos
Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias da Retina/genética , Retinoblastoma/genética , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Transição Epitelial-Mesenquimal/genética , Células HEK293 , Humanos , Camundongos Nus , PTEN Fosfo-Hidrolase/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias da Retina/metabolismo , Neoplasias da Retina/patologia , Retinoblastoma/metabolismo , Retinoblastoma/patologia , Transdução de Sinais , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Prog Retin Eye Res ; 73: 100764, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31173880

RESUMO

Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation of a window for conservative management subject to a "state of metastatic grace" never to be violated. Over the last two decades, conservative management of retinoblastoma witnessed an impressive acceleration of improvements, culminating in two major paradigm shifts in therapeutic strategy. Firstly, the introduction of systemic chemotherapy and focal treatments in the late 1990s enabled radiotherapy to be progressively abandoned. Around 10 years later, the advent of chemotherapy in situ, with the capitalization of new routes of targeted drug delivery, namely intra-arterial, intravitreal and now intracameral injections, allowed significant increase in eye preservation rate, definitive eradication of radiotherapy and reduction of systemic chemotherapy. Here we intend to review the relevant knowledge susceptible to improve the conservative management of retinoblastoma in compliance with the "state of metastatic grace", with particular attention to (i) reviewing how new imaging modalities impact the frontiers of conservative management, (ii) dissecting retinoblastoma genesis, growth patterns, and intraocular routes of tumor propagation, (iii) assessing major therapeutic changes and trends, (iv) proposing a classification of relapsing retinoblastoma, (v) examining treatable/preventable disease-related or treatment-induced complications, and (vi) appraising new therapeutic targets and concepts, as well as liquid biopsy potentiality.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Comorbidade , Tratamento Conservador , Enucleação Ocular , Humanos , Infusões Intra-Arteriais , Injeções Intravítreas , Recidiva Local de Neoplasia , Qualidade de Vida , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Acuidade Visual/fisiologia
19.
JAMA Ophthalmol ; 137(7): 834-837, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31046111

RESUMO

Importance: Bilateral diffuse uveal melanocytic proliferation is a rare sign of several systemic malignant neoplasms. Observations: A patient presenting with uveal melanocytic proliferation underwent a detailed physical examination and extensive imaging. No systemic malignant neoplasm was found. Chorioretinal biopsy was performed, and its immunohistochemical results revealed the presence of primary vitreoretinal lymphoma. Conclusions and Relevance: This patient's results suggest that diffuse uveal melanocytic proliferation may be associated not just with systemic malignant disease, but also with primary intraocular tumors, in this case a primary vitreoretinal lymphoma.


Assuntos
Proliferação de Células , Linfoma Difuso de Grandes Células B/patologia , Melanócitos/patologia , Síndromes Paraneoplásicas Oculares/patologia , Neoplasias da Retina/patologia , Úvea/patologia , Corpo Vítreo/patologia , Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Feminino , Angiofluoresceinografia , Humanos , Infusões Intravenosas , Injeções Intravítreas , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Síndromes Paraneoplásicas Oculares/tratamento farmacológico , Síndromes Paraneoplásicas Oculares/metabolismo , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/metabolismo , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/metabolismo
20.
Ophthalmology ; 126(9): 1306-1314, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30986443

RESUMO

PURPOSE: Attempted eye salvage for unilateral (cT2b/group D) retinoblastoma may risk tumor spread compared with primary enucleation. Identification of clinical features predictive of low histopathologic risk support safe trial salvage. DESIGN: Retrospective, noncomparative single-institutional observational case series. PARTICIPANTS: Children with unilateral cT2b/group D retinoblastoma managed with primary enucleation at the Hospital for Sick Children, Toronto, Canada, January 2008 through February 2018. METHODS: Data included clinical features (intraocular pressure, optic nerve obscuration, macular involvement, tumor seeding, and serous retinal detachment [RD] >1 quadrant), timing to enucleation, histopathologic features, and follow-up. MAIN OUTCOME MEASURES: Primary outcome was low-risk (LR; pT1/pT2) versus high-risk (HR; pT3/pT4) histopathologic features with clinicopathologic correlations. Secondary outcomes were positive predictive (probability that certain clinical features would predict LR histopathologic features) and negative predictive values (probability that absence of these clinical features would predict HR histopathologic features). RESULTS: Thirty-eight eyes were eligible and showed vitreous seeding and normal intraocular pressure. The median diagnosis to enucleation interval was 4 days (range, 0-14 days). Histopathologic analysis diagnosed 4 (10.5%) HR and 34 (89.5%) LR eyes. High-risk eyes demonstrated massive choroidal invasion (4/38) or trans-scleral, extraocular, and postlaminar optic nerve invasion (1/38). Clinical findings included macular involvement (31/38), complete optic nerve obscuration (27/38), and RD (28/38). The proportion of eyes with HR histopathologic features was 13% (4/31; 95% confidence interval [CI], 1%-25%) with macular involvement, 15% (4/27; 95% CI, 1%-28%) with complete optic nerve obscuration, and 14% (4/28; 95% CI, 1%-27%) with RD. The predictability of LR histopathologic features was 100% with macular sparing (7/7; 95% CI, 47%-100%), optic nerve visibility (10/10; 95% CI, 63%-100%), and less than 1 quadrant of RD (10/10; 95% CI, 63%-100%). In 1 child lacking all 3 clinical LR predictive features with HR histopathologic features (pT3a), metastases developed and the patient died; other children are alive and well (mean follow-up, 65 months). CONCLUSIONS: Presence of macular sparing, optic nerve visibility, less than 1 quadrant of RD, or a combination thereof predicted LR histopathologic features at primary enucleation, suggesting safe trial eye salvage. No clinical sign predicted HR histopathologic features.


Assuntos
Neoplasias da Retina/patologia , Retinoblastoma/patologia , Pré-Escolar , Corioide/patologia , Enucleação Ocular , Feminino , Humanos , Lactente , Pressão Intraocular/fisiologia , Imagem por Ressonância Magnética , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Inoculação de Neoplasia , Estadiamento de Neoplasias , Nervo Óptico/patologia , Descolamento Retiniano/diagnóstico , Neoplasias da Retina/diagnóstico por imagem , Neoplasias da Retina/cirurgia , Retinoblastoma/diagnóstico por imagem , Retinoblastoma/cirurgia , Estudos Retrospectivos , Fatores de Risco , Tomografia de Coerência Óptica
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