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AIM: To investigate the role of the transcription factor YY1 in Wilms tumor (WT). PATIENTS & METHODS: We measured YY1 expression using tissue microarray from patients with pediatric renal tumors, mainly WT and evaluated correlations with the predicted clinical evolution. YY1 expression was measured using immunohistochemical and protein expression was determined by digital pathology. RESULTS & CONCLUSION: YY1 significantly increased in WT patients. In addition, an increase in YY1 expression had a greater risk of adverse outcomes in WT patients with favorable histology. YY1 expression was higher in the blastemal component of tumors, and high nuclear expression positively correlated with metastasis. YY1 may be considered as a metastasis risk factor in WT.
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Expresión Génica , Neoplasias Renales/genética , Neoplasias Renales/patología , Factor de Transcripción YY1/genética , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Neoplasias Renales/mortalidad , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Tumor de WilmsRESUMEN
BACKGROUND: miRNAs exert their effect through a negative regulatory mechanism silencing expression upon hybridizing to their target mRNA, and have a prominent position in the control of many cellular processes including carcinogenesis. Previous miRNA studies on retinoblastoma (Rb) have been limited to specific miRNAs reported in other tumors or to medium density arrays. Here we report expression analysis of the whole miRNome on 12 retinoblastoma tumor samples using a high throughput microarray platform including 2578 mature miRNAs. METHODS: Twelve retinoblastoma tumor samples were analyzed using an Affymetrix platform including 2578 mature miRNAs. We applied RMA analysis to normalize raw data, obtained categorical data from detection call values, and also used signal intensity derived expression data. We used Diana-Tools-microT-CDS to find miRNA targets and ChromDraw to map miRNAs in chromosomes. RESULTS: We discovered a core-cluster of 30 miRNAs that were highly expressed in all the cases and a cluster of 993 miRNAs that were uniformly absent in all cases. Another 1022 miRNA were variably present in the samples reflecting heterogeneity between tumors. We explored mRNA targets, pathways and biological processes affected by some of these miRNAs. We propose that the core-cluster of 30 miRs represent miRNA machinery common to all Rb, and affecting most pathways considered hallmarks of cancer. In this core, we identified miR-3613 as a potential and critical down regulatory hub, because it is highly expressed in all the samples and its potential mRNA targets include at least 36 tumor suppressor genes, including RB1. In the variably expressed miRNA, 36 were differentially expressed between males and females. Some of the potential pathways targeted by these 36 miRNAs were associated with hormonal production. CONCLUSION: These findings indicate that Rb tumor samples share a common miRNA expression profile regardless of tumor heterogeneity, and shed light on potential novel therapeutic targets such as mir-3613 This is the first work to delineate the miRNA landscape in retinoblastoma tumor samples using an unbiased approach.
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MicroARNs/genética , Retinoblastoma/genética , Transcriptoma , Adolescente , Adulto , Niño , Análisis por Conglomerados , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos , Reproducibilidad de los Resultados , Retinoblastoma/patología , Factores Sexuales , Adulto JovenRESUMEN
OBJECTS: Epigenetic alterations, known as epimutations, act by deregulating gene expression. These epimutations are reversible through the action of chromatin modifiers such as DNA methylation (DNA-met) and histone deacetylases (HDAC) inhibitors. The present study evaluated the effect of 5-azacitidine (5-aza) and sodium butyrate (NaBu) as inhibitors of DNA-met and HDAC, respectively, in the expression of genes involved in apoptosis. METHODS: D54-MG, U373-MG, and T98G cell lines were exposed to 8 mM of NaBu and 12 µM of 5-aza, as well as a combination of both, for 24 h. The expression of the Bcl-2, Bak-1, Bax, Caspase-3, and Caspase-9 genes was assessed by RT-PCR. RESULTS: They show that the Bcl-2, Caspase-3, and Caspase-9 genes were not expressed by the U373-MG and T98G lines, and that the D54-MG line did not express Bak-1. After treatment, however, these cell lines expressed all of the genes due to the effect of 5-aza on Bak-1 in D54-MG and Caspase-9 in T98G, which suggests repression by DNA-met. Meanwhile, Bcl-2, Caspase-3, and Caspase-9 were in the U373-MG and T98G lines expressed after NaBu treatment. The effect of 5-aza induced an increase in the expression of Bax and Bcl-2, while NaBu produced a similar effect on the Bak-1 and Bax genes. CONCLUSIONS: Results reveal that histone deacetylation is the principle mechanism for repressing these genes and that their basal expression is regulated primarily by this form of histone modification.
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Apoptosis/fisiología , Astrocitoma/genética , Astrocitoma/metabolismo , Epigénesis Genética/fisiología , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , HumanosRESUMEN
PURPOSE: Astrocytomas are the most frequent type of tumor of the central nervous system in children. Hence, it is important to describe markers that may improve our understanding of their behavior. Mature microRNAs (miRNAs) may be such biological markers. They are small molecules of RNA that regulate gene expression post-transcriptionally. Due to their importance in cancer, the objective of the present study was to determine the profile of expression of precursor and mature forms of miR-124-3p, miR-128-1, and miR-221-3p using RT-qPCR in pediatric samples. METHODS: A total of 57 astrocytomas embedded in paraffin were selected. As controls, the study included 13 samples of normal brain tissue. RESULTS: Three of eight miRNAs were selected after a preliminary screening. All the miRNAs showed higher levels of expression in normal brain tissue. The expression of miR-124-3p and miR-128-1 decreased in astrocytomas than in normal brain tissue in all grades (p < 0.05 in both cases), and this reduction was most evident in GIV (407- and 1,469-fold, respectively); however, the expression of the precursor forms pre-miR-128-1 and pre-miR-221 was higher in GIV (3.5-fold) than in GI. The levels of miR-128-1 were higher in infratentorial tumors than in supratentorial cases (p = 0.006). Finally, the expression of miR-221-3p was higher in non-recurrent tumors and live patients (p = 0.0185 and p = 0.0004, respectively). CONCLUSIONS: The low expression of these miRNAs may constitute a potential marker of astrocytomas that correlates with localization, possibly due to alterations in the maturation processes of these miRNAs that produced low mature forms in patients with recurrent pediatric astrocytomas.
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Astrocitoma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , MicroARNs/biosíntesis , Astrocitoma/genética , Biomarcadores de Tumor/genética , Niño , Preescolar , Femenino , Perfilación de la Expresión Génica , Humanos , Lactante , Masculino , México , Clasificación del Tumor , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTS: The protein 300 (p300) and p300/CBP-binding protein-associated factor (PCAF) are enzymes with histone acetyltransferase (HAT) activity, a function that can become deregulated in different tumors and affect biological responses. METHODS: Due to the lack of information on the deregulation of these HATs in pediatric tumors, this study evaluated the expression of both the mRNA and proteins of p300 and PCAF in 54 samples of pediatric astrocytomas embedded in paraffin. RESULTS: PCAF was not expressed in normal brain tissue. In grade I tumors, the expression of p300 (1.1 ± 0.1) and PCAF (1.2 ± 0.11) was greater than those observed in grade III tumors: 0.72 ± 0.15 for p300 and 0.55 ± 0.11 for PCAF, and grade IV tumors: 0.74 ± 0.13 for p300 and 0.55 ± 0.13 for PCAF (p < 0.05). Immunohistochemical staining revealed the same tendency towards a decrease in the expression of the protein as the degree of clinical severity increased. Patients with recurrent grades I, III, and IV tumors had the highest levels of PCAF, compared to those who showed no recurrence (p < 0.05). CONCLUSIONS: This work describes and confirms that these HATs play important roles in regulating genes and in the biological behavior of pediatric astrocytomas.
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Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteína p300 Asociada a E1A/genética , Recurrencia Local de Neoplasia/genética , ARN Mensajero/metabolismo , Factores de Transcripción p300-CBP/genética , Astrocitoma/metabolismo , Astrocitoma/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Niño , Proteína p300 Asociada a E1A/metabolismo , Humanos , Inmunohistoquímica , Clasificación del Tumor , Recurrencia Local de Neoplasia/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción p300-CBP/metabolismoRESUMEN
OBJECTIVE: The objective of this study was to describe the toxicity induced by curcumin in human astrocytoma cell lines. METHODS: The effects induced by curcumin, at 100 µM for 24 h, were evaluated in four astrocytoma cell lines using crystal violet assay and through the evaluation of morphological and ultrastructural changes by electron microscopy. Also, the results of vital staining with acridine orange and propidium iodide for acidic vesicles and apoptotic bodies were analyzed and the expression of the Beclin1 gene was assessed by RT-PCR. RESULTS: The cells treated with curcumin at 100 µM induced an inhibitory concentration50 of viability with morphological changes characterized by a progressive increase in large, non-acidic vesicles devoid of cytoplasmic components and organelles, but that conserved the cell nuclei. No DNA breakage was observed. The astrocytoma cells showed no apoptosis, necrosis or autophagy. Expression of BECLIN1 was not induced (p < 0.05) by curcumin in the astrocytoma cells. CONCLUSIONS: Curcumin at 100 µm induced a new type of death cell in astrocytoma cell lines.
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Antineoplásicos/farmacología , Astrocitos/efectos de los fármacos , Curcumina/farmacología , Antineoplásicos/química , Proteínas Reguladoras de la Apoptosis/genética , Astrocitos/metabolismo , Astrocitos/ultraestructura , Astrocitoma/metabolismo , Astrocitoma/patología , Beclina-1 , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Humanos , Concentración 50 Inhibidora , Proteínas de la Membrana/genética , Microscopía Electrónica de Transmisión , Estructura MolecularRESUMEN
Background: A relatively frequent clinical finding in children is an asymmetric tonsil, which can have multiple etiological possibilities, including a malignant disease. The clinical finding of tonsillar asymmetry is found in approximately 2% of the pediatric population. The incidence of malignancy in the tonsils is low, estimated as 2.5 cases per 10,000 tonsillectomies. Due to its low incidence, the diagnostic tonsillectomy is not justified when tonsillar asymmetry is the only clinical finding. However, it is necessary to identify the critical clinical findings of high suspicion of malignancy that justify the performance of immediate surgery in the pediatric population. Case report: We present the case of a 10-year-old male patient. Four months before admission, the patient started with pharyngodynia and dysphagia, treated as recurrent tonsillitis. Due to exacerbation of the symptoms, orthopnea, and B symptoms, the patient came to consultation; tonsillar asymmetry was observed predominantly on the left side, with exophytic lesions extending to the hypopharynx. We decided to perform an incisional biopsy and tracheostomy due to compromised airway; histopathological diagnosis came back as B-cell lymphoma. Conclusions: Given the clinical scenario of recurrent tonsillitis, unresponsive to conventional medical treatment with antibiotics, tonsillar asymmetry with suspicious tonsillar appearance accompanied by symptoms such as fever, diaphoresis, cervical lymphadenopathy, obstructive symptoms in a pediatric patient, it is necessary to refer the patient to the specialist for timely diagnosis and treatment.
Introducción: La asimetría amigdalina es un hallazgo clínico relativamente frecuente en los niños. Se ha reportado en el 2% de la población pediátrica e incluye múltiples etiologías, entre ellas enfermedad maligna. La incidencia de malignidad es baja: se estima en 2.5 casos por cada 10,000 amigdalectomías. Por tal motivo, cuando se observa asimetría amigdalina como único hallazgo en la exploración física no se justifica la amigdalectomía con fines diagnósticos. Sin embargo, la incertidumbre de malignidad en el médico y en el paciente obliga a considerar los datos clínicos que permitan sospecharla y justificar la intervención quirúrgica. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 10 años. Inició su padecimiento 4 meses previos a su ingreso hospitalario con faringodinia y disfagia, que fueron diagnosticadas y tratadas como amigdalitis recurrente. Acudió al hospital por agudización de los síntomas, evolucionando con ortopnea y síntomas B. En la exploración física se apreció asimetría amigdalina con aumento de volumen en la amígala izquierda extendida hasta la hipofaringe. Se decidió realizar una biopsia incisional y traqueostomía por compromiso respiratorio. El diagnóstico histopatológico fue linfoma de células B. Conclusiones: Ante un paciente pediátrico con amigdalitis recurrente, que no cede al tratamiento médico convencional y presenta asimetría amigdalina con aspecto sospechoso, acompañada de síntomas como fiebre, diaforesis, adenopatías cervicales y síntomas obstructivos, se deberá referir con el especialista para su diagnóstico y tratamiento oportunos.
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Neoplasias , Tonsilectomía , Tonsilitis , Biopsia , Niño , Humanos , Masculino , Tonsila Palatina/cirugía , Tonsilitis/diagnóstico , Tonsilitis/cirugíaRESUMEN
PURPOSE: Expression microarrays are powerful technology that allows large-scale analysis of RNA profiles in a tissue; these platforms include underexploited detection scores outputs. We developed an algorithm using the detection score, to generate a detection profile of shared elements in retinoblastoma as well as to determine its transcriptomic size and structure. METHODS: We analyzed eight briefly cultured primary retinoblastomas with the Human transcriptome array 2.0 (HTA2.0). Transcripts and genes detection scores were determined using the Detection Above Background algorithm (DABG). We used unsupervised and supervised computational tools to analyze detected and undetected elements; WebGestalt was used to explore functions encoded by genes in relevant clusters and performed experimental validation. RESULTS: We found a core cluster with 7,513 genes detected and shared by all samples, 4,321 genes in a cluster that was commonly absent, and 7,681 genes variably detected across the samples accounting for tumor heterogeneity. Relevant pathways identified in the core cluster relate to cell cycle, RNA transport, and DNA replication. We performed a kinome analysis of the core cluster and found 4 potential therapeutic kinase targets. Through analysis of the variably detected genes, we discovered 123 differentially expressed transcripts between bilateral and unilateral cases. CONCLUSIONS: This novel analytical approach allowed determining the retinoblastoma transcriptomic size, a shared active transcriptomic core among the samples, potential therapeutic target kinases shared by all samples, transcripts related to inter tumor heterogeneity, and to determine transcriptomic profiles without the need of control tissues. This approach is useful to analyze other cancer or tissue types.
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Neoplasias de la Retina/genética , Retinoblastoma/genética , Algoritmos , Preescolar , Exones , Femenino , Perfilación de la Expresión Génica , Genes de Retinoblastoma , Genoma Humano , Humanos , Lactante , Masculino , Familia de Multigenes , Fosfotransferasas/genética , Fosfotransferasas/metabolismo , Neoplasias de la Retina/enzimología , Retinoblastoma/enzimología , Transcriptoma , Células Tumorales CultivadasRESUMEN
Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally present with tumors characterized by favorable histology (FHWT), whereas prognosis is poor for the remaining 10% of cases where the tumors are characterized by cellular diffuse anaplasia (DAWT). Relatively few studies have investigated microRNA-related epigenetic regulation and its relationship with altered gene expression in WT. Here, we aim to identify microRNAs differentially expressed in WT and describe their expression in terms of cellular anaplasia, metastasis, and association with the main genetic alterations in WT to identify potential prognostic biomarkers. Expression profiling using TaqMan low-density array was performed in a discovery cohort consisting of four DAWT and eight FHWT samples. Relative quantification resulted in the identification of 109 (48.7%) microRNAs differentially expressed in both WT types. Of these, miR-10a-5p, miR-29a-3p, miR-181a-5p, miR-200b-3p, and miR-218-5p were selected and tested by RT-qPCR on a validation cohort of 53 patient samples. MiR-29a and miR-218 showed significant differences in FHWT with low (P = 0.0018) and high (P = 0.0131) expression, respectively. To discriminate between miRNA expression FHWTs and healthy controls, the receiver operating characteristic (ROC) curves were obtained; miR-29a AUC was 0.7843. Furthermore, low expression levels of miR-29a and miR-200b (P = 0.0027 and P = 0.0248) were observed in metastatic tumors. ROC curves for miR-29a discriminated metastatic patients (AUC = 0.8529) and miR-200b (AUC = 0.7757). To confirm the differences between cases with poor prognosis, we performed in situ hybridization for three microRNAs in five DAWT and 17 FHWT samples, and only significant differences between adjacent tissues and FHWT tumors were found for miR-181a, miR-200b, and miR-218, in both total pixels and nuclear analyses. Analysis of copy number variation in genes showed that the most prevalent alterations were WTX (47%), IGF2 (21%), 1q (36%) gain, 1p36 (16%), and WTX deletion/1q duplicate (26%). The five microRNAs evaluated are involved in the Hippo signaling pathway and participate in Wilms tumor development through their effects on differentiation, proliferation, angiogenesis, and metastasis.
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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.
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Vesículas Extracelulares/metabolismo , MicroARNs/sangre , Neoplasias de la Retina/patología , Retinoblastoma/patología , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Preescolar , MicroARN Circulante/sangre , Análisis por Conglomerados , Análisis Discriminante , Femenino , Humanos , Lactante , Masculino , MicroARNs/análisis , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias de la Retina/genética , Retinoblastoma/genéticaRESUMEN
Introduction: Congenital pulmonary malformations are a rare cause of neonatal morbidity. Some of them have a common origin, which allows the identification of combined lesions. Its diagnosis can be made prenatally by ultrasound, with the limitation that this study is performed in specialized centers and depends on the expertise of the operator. The association of pulmonary sequestration and congenital malformation of the airway has been described in approximately 40-60 cases since its first description in 1949. Many lesions are not perceptible in intrauterine life and in the neonatal period there are recurrent respiratory symptoms that in some cases are associated with a congenital pulmonary malformation. Case report: We report the case of a young infant, who was diagnosed with pulmonary sequestration at 24 weeks of gestational age, undergoing intrauterine surgical treatment with a report of complete resolution of the malformation in posterior ultrasounds. She was valued by pediatric pneumology at 4 months of age, where angiotomography was performed and the presence of pulmonary sequestration was confirmed by lobectomy. The histopathological study reported extralobar pulmonary sequestration with congenital malformation of the pulmonary airway type 2. These combined lesions were identified by histopathological study. The treatment of choice was surgical. Conclusions: Upon the confirmation of a malformation, we emphasize the importance of performing a screening in order to search for other that could be associated.
Introducción: Las malformaciones pulmonares congénitas son una causa poco frecuente de morbilidad neonatal. Algunas de ellas tienen un origen común, lo que permite identificar lesiones combinadas. Su diagnóstico puede realizarse de forma prenatal mediante ultrasonido, con las limitaciones de que solo se realiza en centros especializados y que depende de la pericia del operador. La asociación entre el secuestro pulmonar y la malformación congénita de la vía aérea se ha descrito aproximadamente en 40-60 casos desde 1949, cuando se observó por primera vez. Muchas lesiones no son perceptibles en la vida intrauterina. Sin embargo, en el periodo neonatal se presentan síntomas respiratorios recurrentes que en algunos casos están asociados con una malformación pulmonar. Caso clínico: Se presenta el caso de una lactante diagnosticada con secuestro pulmonar a las 24 semanas de edad gestacional. Recibió tratamiento quirúrgico intrauterino con reporte de resolución completa de la malformación en ultrasonidos posteriores. Fue valorada por neumología pediátrica a los 4 meses de edad. Se realizó una angiotomografía y se confirmó la presencia de secuestro pulmonar, por lo que se realizó una lobectomía. El estudio histopatológico reportó secuestro pulmonar extralobar con malformación congénita de la vía aérea pulmonar tipo 2. Estas lesiones combinadas se identificaron mediante un estudio histopatológico. El tratamiento de elección fue quirúrgico. Conclusiones: Ante la confirmación de una malformación, destaca la importancia de realizar la búsqueda de otras malformaciones que pudieran estar asociadas.
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Secuestro Broncopulmonar/diagnóstico , Diagnóstico Prenatal/métodos , Anomalías del Sistema Respiratorio/diagnóstico , Secuestro Broncopulmonar/cirugía , Angiografía por Tomografía Computarizada/métodos , Femenino , Terapias Fetales/métodos , Edad Gestacional , Humanos , Lactante , Neumonectomía/métodos , Anomalías del Sistema Respiratorio/cirugíaRESUMEN
In humans, recessive loss-of-function mutations in STAT1 are associated with mycobacterial and viral infections, whereas gain-of-function (GOF) mutations in STAT1 are associated with a type of primary immunodeficiency related mainly, but not exclusively, to chronic mucocutaneous candidiasis (CMC). We studied and established a molecular diagnosis in a pediatric patient with mycobacterial infections, associated with CMC. The patient, daughter of a non-consanguineous mestizo Mexican family, had axillary adenitis secondary to BCG vaccination and was cured with resection of the abscess at 1-year old. At the age of 4 years, she had a supraclavicular abscess with acid-fast-staining bacilli identified in the soft tissue and bone, with clinical signs of disseminated infection and a positive Gene-X-pert test, which responded to anti-mycobacterial drugs. Laboratory tests of the IL-12/interferon gamma (IFN-γ) circuit showed a higher production of IL-12p70 in the whole blood from the patient compared to healthy controls, when stimulated with BCG and BCG + IFN-γ. The whole blood of the patient produced 35% less IFN-γ compared to controls assessed by ELISA and flow cytometry, but IL-17 producing T cells from patient were almost absent in PBMC stimulated with PMA plus ionomycin. Signal transduction and activator of transcription 1 (STAT1) was hyperphosphorylated at tyrosine 701 in response to IFN-γ and -α, as demonstrated by flow cytometry and Western blotting in fresh blood mononuclear cells and in Epstein-Barr virus lymphoblastoid cell lines (EBV-LCLs); phosphorylation of STAT1 in EBV-LCLs from the patient was resistant to inhibition by staurosporine but sensitive to ruxolitinib, a Jak phosphorylation inhibitor. Genomic DNA sequencing showed a de novo mutation in STAT1 in cells from the patient, absent in her parents and brother; a known T385M missense mutation in the DNA-binding domain of the transcription factor was identified, and it is a GOF mutation. Therefore, GOF mutations in STAT1 can induce susceptibility not only to fungal but also to mycobacterial infections by mechanisms to be determined.
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Abstract Background: A relatively frequent clinical finding in children is an asymmetric tonsil, which can have multiple etiological possibilities, including a malignant disease. The clinical finding of tonsillar asymmetry is found in approximately 2% of the pediatric population. The incidence of malignancy in the tonsils is low, estimated as 2.5 cases per 10,000 tonsillectomies. Due to its low incidence, the diagnostic tonsillectomy is not justified when tonsillar asymmetry is the only clinical finding. However, it is necessary to identify the critical clinical findings of high suspicion of malignancy that justify the performance of immediate surgery in the pediatric population. Case report: We present the case of a 10-year-old male patient. Four months before admission, the patient started with pharyngodynia and dysphagia, treated as recurrent tonsillitis. Due to exacerbation of the symptoms, orthopnea, and B symptoms, the patient came to consultation; tonsillar asymmetry was observed predominantly on the left side, with exophytic lesions extending to the hypopharynx. We decided to perform an incisional biopsy and tracheostomy due to compromised airway; histopathological diagnosis came back as B-cell lymphoma. Conclusions: Given the clinical scenario of recurrent tonsillitis, unresponsive to conventional medical treatment with antibiotics, tonsillar asymmetry with suspicious tonsillar appearance accompanied by symptoms such as fever, diaphoresis, cervical lymphadenopathy, obstructive symptoms in a pediatric patient, it is necessary to refer the patient to the specialist for timely diagnosis and treatment.
Resumen Introducción: La asimetría amigdalina es un hallazgo clínico relativamente frecuente en los niños. Se ha reportado en el 2% de la población pediátrica e incluye múltiples etiologías, entre ellas enfermedad maligna. La incidencia de malignidad es baja: se estima en 2.5 casos por cada 10,000 amigdalectomías. Por tal motivo, cuando se observa asimetría amigdalina como único hallazgo en la exploración física no se justifica la amigdalectomía con fines diagnósticos. Sin embargo, la incertidumbre de malignidad en el médico y en el paciente obliga a considerar los datos clínicos que permitan sospecharla y justificar la intervención quirúrgica. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 10 años. Inició su padecimiento 4 meses previos a su ingreso hospitalario con faringodinia y disfagia, que fueron diagnosticadas y tratadas como amigdalitis recurrente. Acudió al hospital por agudización de los síntomas, evolucionando con ortopnea y síntomas B. En la exploración física se apreció asimetría amigdalina con aumento de volumen en la amígala izquierda extendida hasta la hipofaringe. Se decidió realizar una biopsia incisional y traqueostomía por compromiso respiratorio. El diagnóstico histopatológico fue linfoma de células B. Conclusiones: Ante un paciente pediátrico con amigdalitis recurrente, que no cede al tratamiento médico convencional y presenta asimetría amigdalina con aspecto sospechoso, acompañada de síntomas como fiebre, diaforesis, adenopatías cervicales y síntomas obstructivos, se deberá referir con el especialista para su diagnóstico y tratamiento oportunos.
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BACKGROUND: Sarcoidosis is a systemic disease of unknown etiology that rarely occurs in children. It usually affects the lungs, however, it may involve various organs. It occasionally affects the general condition, and causes fever, hepatomegaly and splenomegaly. CASE REPORT: We report the case of a twelve-year-old adolescent with late-onset childhood sarcoidosis which diagnosis was confirmed by lymph node histopathological study. The patient presented general condition, hypercalcemia, erythema nodosum, severe lung disorders, lymphadenopathy, hepatomegaly and testicular mass. He received treatment with steroids, with excellent clinical response. CONCLUSIONS: We highlight the importance of considering the diagnosis of sarcoidosis in patients with hepatomegaly, lymphadenopathy, diffuse lung damage, erythema nodosum, testicular mass and hypercalcemia, as well as the need for a multidisciplinary approach to assess multiple organ involvement and the early beginning of steroid treatment in order to prevent the progression of the disease.
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BACKGROUND: Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal. CASE REPORT: We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient. CONCLUSIONS: The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications.
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BACKGROUND AND AIMS: Recurrent and specific chromosomal translocations have been described in four pediatric sarcomas belonging to the small round blue cell (SRBC) group of tumors. Identification of mRNA chimeras using RT-PCR discriminates among alveolar rhabdomyosarcoma (ARMS), Ewing's sarcoma (ES/pPNET), synovial sarcoma (SS) and desmoplastic small round cell tumor (DSRCT); however, frequencies of these translocations are variable. We present a retrospective study comparing histological examination and occurrence of major chromosomal translocations to validate the diagnosis and to assess the frequency of these molecular markers in a group of 92 small round blue cell (SRBC) tumor samples from Hospital Infantil de Mexico. METHODS: We tested a panel of RT-PCR assays to each RNA tumor sample from formalin-fixed, paraffin-embedded tumors to detect specific mRNA chimeras in 47 ES/pPNET, 19 ARMS, four SS, three DSRCT, and 19 other SRBC tumors. RESULTS: After excluding poor RNA quality samples, we found translocations in 17/31 ES/pPNET (54.8%), 10/19 ARMS (52.6%), 4/4 SS (100%) and 4/4 DSRCT (100%). We found disagreement in only three samples: one ES/pPNET and one embryonal rhabdomyosarcoma harbor a PAX3-FOXO1 translocation (for ARMS), and one neuroepithelioma harboring a EWS-WT1 (for DSRCT). Unsuitable RNA was found in 20/92 samples (21.7%) and was related to necrosis, small amount of tumor tissue, and use of nitric acid in bone biopsies, but was not related to age of the block. CONCLUSIONS: We found a significantly lower occurrence of chromosomal translocations in ES/pPNET compared to reports from other groups. Differences may exist in the frequencies of these molecular markers among different populations.
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Sarcoma/genética , Translocación Genética , Niño , Tumor Desmoplásico de Células Pequeñas Redondas/genética , Tumor Desmoplásico de Células Pequeñas Redondas/patología , Humanos , Tumores Neuroectodérmicos Periféricos Primitivos/genética , Tumores Neuroectodérmicos Periféricos Primitivos/patología , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Sarcoma/patología , Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologíaRESUMEN
Resumen Introducción: Las malformaciones pulmonares congénitas son una causa poco frecuente de morbilidad neonatal. Algunas de ellas tienen un origen común, lo que permite identificar lesiones combinadas. Su diagnóstico puede realizarse de forma prenatal mediante ultrasonido, con las limitaciones de que solo se realiza en centros especializados y que depende de la pericia del operador. La asociación entre el secuestro pulmonar y la malformación congénita de la vía aérea se ha descrito aproximadamente en 40-60 casos desde 1949, cuando se observó por primera vez. Muchas lesiones no son perceptibles en la vida intrauterina. Sin embargo, en el periodo neonatal se presentan síntomas respiratorios recurrentes que en algunos casos están asociados con una malformación pulmonar. Caso clínico: Se presenta el caso de una lactante diagnosticada con secuestro pulmonar a las 24 semanas de edad gestacional. Recibió tratamiento quirúrgico intrauterino con reporte de resolución completa de la malformación en ultrasonidos posteriores. Fue valorada por neumología pediátrica a los 4 meses de edad. Se realizó una angiotomografía y se confirmó la presencia de secuestro pulmonar, por lo que se realizó una lobectomía. El estudio histopatológico reportó secuestro pulmonar extralobar con malformación congénita de la vía aérea pulmonar tipo 2. Estas lesiones combinadas se identificaron mediante un estudio histopatológico. El tratamiento de elección fue quirúrgico. Conclusiones: Ante la confirmación de una malformación, destaca la importancia de realizar la búsqueda de otras malformaciones que pudieran estar asociadas.
Abstract Introduction: Congenital pulmonary malformations are a rare cause of neonatal morbidity. Some of them have a common origin, which allows the identification of combined lesions. Its diagnosis can be made prenatally by ultrasound, with the limitation that this study is performed in specialized centers and depends on the expertise of the operator. The association of pulmonary sequestration and congenital malformation of the airway has been described in approximately 40-60 cases since its first description in 1949. Many lesions are not perceptible in intrauterine life and in the neonatal period there are recurrent respiratory symptoms that in some cases are associated with a congenital pulmonary malformation. Case report: We report the case of a young infant, who was diagnosed with pulmonary sequestration at 24 weeks of gestational age, undergoing intrauterine surgical treatment with a report of complete resolution of the malformation in posterior ultrasounds. She was valued by pediatric pneumology at 4 months of age, where angiotomography was performed and the presence of pulmonary sequestration was confirmed by lobectomy. The histopathological study reported extralobar pulmonary sequestration with congenital malformation of the pulmonary airway type 2. These combined lesions were identified by histopathological study. The treatment of choice was surgical. Conclusions: Upon the confirmation of a malformation, we emphasize the importance of performing a screening in order to search for other that could be associated.
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Femenino , Humanos , Lactante , Diagnóstico Prenatal/métodos , Anomalías del Sistema Respiratorio/diagnóstico , Secuestro Broncopulmonar/diagnóstico , Neumonectomía/métodos , Anomalías del Sistema Respiratorio/cirugía , Secuestro Broncopulmonar/cirugía , Edad Gestacional , Terapias Fetales/métodos , Angiografía por Tomografía Computarizada/métodosRESUMEN
Cronobacter spp. are opportunistic pathogens linked to lie-threatening infections in neonates and contaminated powdered infant formula that has been epidemiologically associated with these cases. Clinical symptoms of Cronobacter include necrotizing enterocolitis, bacteremia, and meningitis. Flagella from C. sakazakii are involved in biofilm formation and its adhesion to epithelial cells. We investigated the role of flagella from C. sakazakii ST1 and ST4, C. malonaticus, C. muytjensii, C. turicensis and C. dublinensis during the activation of cytokines (IL-8, TNF-α, and IL-10) in macrophage derivatives from human monocytes, which has not been extensively studied. The production and identity of flagella from the five Cronobacter species were visualized and recognized with anti-flagella antibodies by immunogold labeling through transmission electron microscopy. Purified flagella were dissociated into monomers in 12% SDS-PAGE Coomassie blue-stained gels showing a band of â¼28 kDa and, in addition, mass spectrometry revealed the presence of several peptides that correspond to flagellin. Flagella (100 ng) induced the release of IL-8 (3314-6025 pg/ml), TNF-α (39-359 pg/ml), and IL-10 (2-96 pg/ml), in macrophage isolates from human monocytes and similar results were obtained when flagella were dissociated into monomers. Inhibition assays using three dilutions of anti-flagella antibodies (1â¶10, 1â¶100, and 1â¶200) suppressed the secretion of IL-8, TNF-α, and IL-10 between 95-100% using 100 ng of protein. A transfection assay using 293-hTLR5 cells showed IL-8 release of 197 pg/ml and suppression in the secretion of IL-8 when anti-hTLR5-IgA antibodies were used at different concentrations. These observations suggest that flagella and flagellin are involved in an inflammatory response dependent on TLR5 recognition, which could contribute to the pathogenesis of the bacteria.
Asunto(s)
Cronobacter/inmunología , Citocinas/metabolismo , Flagelos/inmunología , Mediadores de Inflamación/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Secuencia de Aminoácidos , Anticuerpos/inmunología , Anticuerpos/farmacología , Cronobacter/ultraestructura , Flagelos/química , Flagelos/efectos de los fármacos , Flagelos/ultraestructura , Flagelina/química , Células HEK293 , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina A/farmacología , Macrófagos/citología , Datos de Secuencia Molecular , Monocitos/citología , Alineación de Secuencia , Receptor Toll-Like 5/antagonistas & inhibidores , Receptor Toll-Like 5/inmunologíaRESUMEN
Resumen: Introducción: La sarcoidosis es una enfermedad sistémica de etiología desconocida que raramente se presenta en la infancia. Generalmente afecta los pulmones; sin embargo, puede involucrar diversos órganos. Ocasionalmente afecta el estado general, y origina fiebre, hepatomegalia y esplenomegalia. Caso clínico: Se presenta el caso de un adolescente de doce años de edad con sarcoidosis infantil de inicio tardío, cuyo diagnóstico fue confirmado con un estudio histopatológico de ganglio linfático. El paciente cursó con afección general, hipercalcemia, eritema nodoso, alteraciones pulmonares graves, adenopatías, hepatomegalia y masa testicular. Recibió tratamiento con esteroides, con excelente respuesta clínica. Conclusiones: Se resalta la importancia de considerar el diagnóstico de sarcoidosis en los pacientes con hepatomegalia, adenopatías, daño pulmonar difuso, eritema nodoso, masa testicular e hipercalcemia, así como la necesidad del abordaje multidisciplinario para valorar el compromiso orgánico múltiple y el inicio oportuno de la terapia con esteroides, con el fin de evitar la progresión de la enfermedad.
Abstract: Background: Sarcoidosis is a systemic disease of unknown etiology that rarely occurs in children. It usually affects the lungs, however, it may involve various organs. It occasionally affects the general condition, and causes fever, hepatomegaly and splenomegaly. Case report: We report the case of a twelve-year-old adolescent with late-onset childhood sarcoidosis which diagnosis was confirmed by lymph node histopathological study. The patient presented general condition, hypercalcemia, erythema nodosum, severe lung disorders, lymphadenopathy, hepatomegaly and testicular mass. He received treatment with steroids, with excellent clinical response. Conclusions: We highlight the importance of considering the diagnosis of sarcoidosis in patients with hepatomegaly, lymphadenopathy, diffuse lung damage, erythema nodosum, testicular mass and hypercalcemia, as well as the need for a multidisciplinary approach to assess multiple organ involvement and the early beginning of steroid treatment in order to prevent the progression of the disease.