Ventriculomegalia bilateral grave diagnosticada em feto no terceiro trimestre: relato de caso e revisão da literatura

La ventriculomegalia fetal (VM) se define como un aumento de los diámetros de los ventrículos laterales mayor a 10 mm en un ultrasonido prenatal. Presenta una incidencia de 0,3 a 1,5 por cada 1000 nacimientos. El hallazgo ultrasonográfico generalmente ocurre durante la exploración en el segundo trimestre, asociado a malformaciones del sistema nervioso central (SNC), eventos disruptivos o síndromes genéticos. Clasificación en 1 o 2 maneras: leve (10-15 mm) o grave (>15 mm), ó leve (10-12 mm), moderada (13-15 mm) o grave (>15 mm). Paciente de 26 años, con un embarazo pretérmino, mal control prenatal, ingresó con trabajo de parto pretérmino. Signos vitales estables, feto único, vivo, ultrasonido obstétrico con reporte de VM bilateral severa. Se decidió comenzar protocolo para resolución de embarazo vía abdominal de urgencia, se obtuvo recién nacido del sexo masculino en paro cardiorrespiratorio, no se brindaron maniobras de reanimación neonatal. Este hallazgo es solo un paso previo para realizar durante el abordaje diagnóstico con el fin de reconocer la causa de la dilatación ventricular. Cuando no se encuentra ninguna causa, se define como "aislada", representando, por definición, una discriminación provisional de exclusión.Fetal ventriculomegaly (VM) is defined as an increase in the diameters of the lateral ventricles greater than 10 mm on a prenatal ultrasound. It has an incidence of 0.3 to 1.5 per 1000 births. The ultrasonographic finding generally occurs during the examination in the second trimester, associated with malformations of the central nervous system (CNS), disruptive events or genetic syndromes. Classification in 1 or 2 ways: mild (10-15 mm) or severe (>15 mm), or mild (10-12 mm), moderate (13-15 mm) or severe (>15 mm). A 26-year-old patient, with a preterm pregnancy, poor prenatal control, was admitted with preterm labor. Stable vital signs, single fetus, alive, obstetric ultrasound with report of severe bilateral VM. It was decided to begin a protocol for resolving the pregnancy via an emergency abdominal route, a male newborn was obtained in cardiorespiratory arrest, neonatal resuscitation maneuvers were not provided. This finding is only a preliminary step to take during the diagnostic approach to recognize the cause of ventricular dilation. When no cause is found, it is defined as "isolated", representing, by definition, provisional discrimination of exclusion.Ventriculomegalia fetal (VM) é definida como um aumento nos diâmetros dos ventrículos laterais superior a 10 mm na ultrassonografia pré-natal. Tem uma incidência de 0,3 a 1,5 por 1.000 nascimentos. O achado ultrassonográfico geralmente ocorre durante o exame do segundo trimestre, associado a malformações do sistema nervoso central (SNC), eventos disruptivos ou síndromes genéticas. Classificação em 1 ou 2 formas: leve (10-15 mm) ou grave (>15 mm), ou leve (10-12 mm), moderada (13-15 mm) ou grave (>15 mm). Paciente de 26 anos, com gravidez prematura, mau controle pré-natal, foi internada em trabalho de parto prematuro. Sinais vitais estáveis, feto único, vivo, ultrassonografia obstétrica com relato de MV bilateral grave. Optou-se por iniciar protocolo de resolução da gravidez por via abdominal de emergência, um recém-nascido do sexo masculino foi obtido em parada cardiorrespiratória, não foram realizadas manobras de reanimação neonatal. Este achado é apenas um passo preliminar durante a abordagem diagnóstica para reconhecer a causa da dilatação ventricular. Quando nenhuma causa é encontrada, ela é definida como “isolada”, representando, por definição, uma discriminação provisória de exclusão

HypoxamiRs Profiling Identify miR-765 as a Regulator of the Early Stages of Vasculogenic Mimicry in SKOV3 Ovarian Cancer Cells

Vasculogenic mimicry (VM) is a novel cancer hallmark in which malignant cells develop matrix-associated 3D tubular networks with a lumen under hypoxia to supply nutrients needed for tumor growth. Recent studies showed that microRNAs (miRNAs) may have a role in VM regulation. In this study, we examined the relevance of hypoxia-regulated miRNAs (hypoxamiRs) in the early stages of VM formation. Data showed that after 48 h hypoxia and 12 h incubation on matrigel SKOV3 ovarian cancer cells undergo the formation of matrix-associated intercellular connections referred hereafter as 3D channels-like structures, which arose previous to the apparition of canonical tubular structures representative of VM. Comprehensive profiling of 754 mature miRNAs at the onset of hypoxia-induced 3D channels-like structures showed that 11 hypoxamiRs were modulated (FC>1.5; p < 0.05) in SKOV3 cells (9 downregulated and 2 upregulated). Bioinformatic analysis of the set of regulated miRNAs showed that they might impact cellular pathways related with tumorigenesis. Moreover, overall survival analysis in a cohort of ovarian cancer patients (n = 485) indicated that low miR-765, miR-193b, miR-148a and high miR-138 levels were associated with worst patients outcome. In particular, miR-765 was severely downregulated after hypoxia (FC < 32.02; p < 0.05), and predicted to target a number of protein-encoding genes involved in angiogenesis and VM. Functional assays showed that ectopic restoration of miR-765 in SKOV3 cells resulted in a significant inhibition of hypoxia-induced 3D channels-like formation that was associated with a reduced number of branch points and patterned tubular-like structures. Mechanistic studies confirmed that miR-765 decreased the levels of VEGFA, AKT1 and SRC-α transducers and exerted a negative regulation of VEGFA by specific binding to its 3‘UTR. Finally, overall survival analysis of a cohort of ovarian cancer patients (n = 1435) indicates that high levels of VEGFA, AKT1 and SRC-α and low miR-765 expression were associated with worst patients outcome. In conclusion, here we reported a novel hypoxamiRs signature which constitutes a molecular guide for further clinical and functional studies on the early stages of VM. Our data also suggested that miR-765 coordinates the formation of 3D channels-like structures through modulation of VEGFA/AKT1/SRC-α axis in SKOV3 ovarian cancer cells

MicroRNA-204 Regulates Angiogenesis and Vasculogenic Mimicry in CD44+/CD24− Breast Cancer Stem-like Cells

Tumors have high requirements in terms of nutrients and oxygen. Angiogenesis is the classical mechanism for vessel formation. Tumoral vascularization has the function of nourishing the cancer cells to support tumor growth. Vasculogenic mimicry, a novel intratumoral microcirculation system, alludes to the ability of cancer cells to organize in three-dimensional (3D) channel-like architectures. It also supplies the tumors with nutrients and oxygen. Both mechanisms operate in a coordinated way; however, their functions in breast cancer stem-like cells and their regulation by microRNAs remain elusive. In the present study, we investigated the functional role of microRNA-204 (miR-204) on angiogenesis and vasculogenic mimicry in breast cancer stem-like cells. Using flow cytometry assays, we found that 86.1% of MDA-MB-231 and 92% of Hs-578t breast cancer cells showed the CD44+/CD24− immunophenotype representative of cancer stem-like cells (CSCs). The MDA-MB-231 subpopulation of CSCs exhibited the ability to form mammospheres, as expected. Interestingly, we found that the restoration of miR-204 expression in CSCs significantly inhibited the number and size of the mammospheres. Moreover, we found that MDA-MB-231 and Hs-578t CSCs efficiently undergo angiogenesis and hypoxia-induced vasculogenic mimicry in vitro. The transfection of precursor miR-204 in both CSCs was able to impair the angiogenesis in the HUVEC cell model, which was observed as a diminution in the number of polygons and sprouting cells. Remarkably, miR-204 mimics also resulted in the inhibition of vasculogenic mimicry formation in MDA-MB-231 and Hs-578t CSCs, with a significant reduction in the number of channel-like structures and branch points. Mechanistically, the effects of miR-204 were associated with a diminution of pro-angiogenic VEGFA and β-catenin protein levels. In conclusion, our findings indicated that miR-204 abrogates the angiogenesis and vasculogenic mimicry development in breast cancer stem-like cells, suggesting that it could be a potential tool for breast cancer intervention based on microRNA replacement therapies

Ciencia Odontológica

Es para los integrantes de la Red de Investigación en Estomatología (RIE) una enorme alegría presentar el primero de una serie de 5 libros sobre casos clínicos, revisiones de la literatura e investigaciones. La RIE está integrada por cuerpos académicos de la Universidad Autónoma del Estado de Hidalgo, Universidad Autónoma del Estado de México, Universidad Autónoma de Campeche y Universidad de Guadalajara