Miriam González‐Gómez

Universidad de La Laguna

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Ricardo Gutiérrez

Universidad de La Laguna

Lucio Díaz‐Flores

Universidad de La Laguna

José Luís Carrasco

Universidad de La Laguna

Juan Francisco Madrid

Universidad de Murcia

Gundela Meyer

Universidad de La Laguna

Rafael Alonso

Research Institute Hospital 12 de Octubre

Raquel Marín

Universidad de La Laguna

Mario Dı́az

Universidad de Guanajuato

Francisco José Sáez

University of the Basque Country

HÁ

Hugo Álvarez‐Argüelles

Universidad de La Laguna

Cooperative Institutions

Universidad de La Laguna

University of Bologna

Institute for Biomedical Engineering

European Institute of Oncology

Malmö University

Hospital de Tortosa Virgen de la Cinta

Hospital Universitario de Canarias

Instituto de Salud Carlos III

Complexo Hospitalar Universitário Professor Edgard Santos

Universidade Federal da Bahia

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P20.15.A DESCRIPTIVE ANALYSIS OF A SERIES OF H3 K27-ALTERED DIFFUSE MIDLINE GLIOMAS IN CHILDREN AND ADULT POPULATION

Neuro-Oncology (2023)

C. Salva de Torres Daniel Lopez Valbuena Miriam González‐Gómez María Vieito

Abstract BACKGROUND Molecular biomarkers have gained importance in providing diagnostic information for brain and spinal cord tumors. Diffuse midline gliomas (DMG) are now defined as H3 K27-altered. H3 K27M mutations were first described in pediatric diffuse pontine gliomas but can also be encountered in adult gliomas. The H3 K27M mutation often co-occurs with mutations in TP53, PDGFR, or ACVR1 and is mutually exclusive to IDH1/2 mutations and 1p/19q co-deletion. Surgical resection is often not feasible for its localization and the benefit of temozolomide (TMZ) is not clear as they are MGMT unmethylated; all of it conferring a poor prognosis. It has been suggested that pediatric patients (pts) have worse outcomes. Our aim was to describe pts with H3 K27-altered gliomas to better understand the characteristics of this population. MATERIAL AND METHODS We analyzed clinical, histological and molecular features of 6 adults and 10 pediatric pts diagnosed with H3 K27M-mutant gliomas between May 2016 and January 2021 in a tertiary hospital in Barcelona. RESULTS For adults, mean age at diagnosis was 34.6 years (range = 20 - 55 years). For children, mean age was 11.2 years (range = 4 - 17 years). Male-to-female ratio was 1:1. Tumors involved thalamus (adult = 3; pediatric = 3), pons (adult = 1; pediatric = 6), and pineal region (n = 1). Ki67 range was 2-60% (pediatric mean 32%, adult mean 20%). A molecular panel was analyzed in 8 pediatric pts and 1 adult. No EGFR amplifications were detected.Three of them had TP53 mutations and 2 had PDGFRA amplification. Only 2 pediatric pts had MGMT methylation. Regarding treatment, 9 pediatric and 4 adult pts underwent radiotherapy and TMZ as first-line, with a mean time to intervention of 5.6 months. One child went through palliative care. As a second-line treatment, re-irradiation was used in 3 pediatric pts and irinotecan-bevacizumab was used in 2 adults. One adult received up to 4 different treatments (TMZ chemoradiotherapy followed by adjuvant TMZ, irinotecan-bevacizumab, lomustine and metronomic TMZ).All 9 pediatric pts died, with a mean OS of 12.0 months. Among adults, 2 pts died, 10.5 and 31.2 months after diagnosis, 1 has progressed to first-line and is receiving PCV as second-line treatment, and 1 has completed Stupp regimen with stable disease as best response. CONCLUSION Although the sample size is limited, our cohort data resembles what has been previously reported in terms of clinical and molecular characteristics: diagnosed in young adults and pediatric pts, characterized by a midline location, a low rate of MGMT promoter methylation, frequent TP53 and PDGFR alterations, and poor prognosis. There is currently no consensus on optimal treatment sequence or best treatment for these pts. Collaborative effort and participation in clinical trials are needed to keep advancing in this poor prognosis disease.

Temozolomide

10.1093/neuonc/noad137.441

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VDAC and ERα interaction in caveolae from human cortex is altered in Alzheimer's disease

Molecular and Cellular Neuroscience (2009)

Cristina M. Ramírez Miriam González‐Gómez Mario Dı́az Rafael Alonso Isidró Ferrer

Voltage-dependent anion channel

VDAC1

Neurotoxicity

Caveolin

Caveolin 1

10.1016/j.mcn.2009.07.001

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Neuroblastoma in Spain: Linking the national clinical database and epidemiological registries – A study by the Joint Action on Rare Cancers

Cancer Epidemiology (2022)

Adela Cañete Rafael Peris‐Bonet Riccardo Capocaccia Elena Pardo-Romaguera Vanessa Segura

Linkage between clinical databases and population-based cancer registries may serve to evaluate European Reference Networks' (ERNs) activity, by monitoring the proportion of patients benefiting from these and their impact on survival at a population level. To test this, a study targeting neuroblastoma (Nb) was conducted in Spain by the European Joint Action on Rare Cancers.Subjects: Nb cases, incident 1999-2017, aged < 15 years. Linkage included: Spanish Neuroblastoma Clinical Database (NbCDB) (1217 cases); Spanish Registry of Childhood Tumours (RETI) (1514 cases); and 10 regional population-based registries (RPBCRs) which cover 33% of the childhood population (332 cases). Linkage was semiautomatic. We estimated completeness, incidence, contribution, deficit, and 5-year survival in the databases and specific subsets.National completeness estimates for RETI and NbCDB were 91% and 72% respectively, using the Spanish RPBCRs on International Incidence of Childhood Cancer (https://iicc.iarc.fr/) as reference. RPBCRs' specific contribution was 1.6%. Linkage required manual crossover in 54% of the semiautomatic matches. Five-year survival was 74% (0-14 years) and 90% (0-18 months).All three databases were incomplete as regards Spain as a whole and should therefore be combined to achieve full childhood cancer registration. A unique personal patient identifier could facilitate such linkage. Most children have access to Nb clinical trials. Consolidated interconnections between the national registry and clinical registries (including ERNs and paediatric oncology clinical groups) should be established to evaluate outcomes.

Record Linkage

Linkage (software)

10.1016/j.canep.2022.102145

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Reproductive outcomes according to estradiol levels on the day of gonadotropin-releasing hormone agonist triggering in oocyte donation cycles

Fertility and Sterility (2015)

Guillermo Quea Clément Jimenez A. Cearsolo Miriam González‐Gómez Teresa Ganzabal

Hormone antagonist

Oocyte donation

10.1016/j.fertnstert.2015.07.687

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Dynamic expression of the p53 family members p63 and p73 in the mouse and human telencephalon during development and in adulthood

Brain Research (2010)

Nieves Carolina Hernandez-Acosta Alfredo Cabrera‐Socorro Mercedes Pueyo Morlans Francisco J. González Delgado M. Luisa Suárez-Solá

Doublecortin

Ganglionic eminence

Calretinin

Cell fate determination

10.1016/j.brainres.2010.11.041

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The Subpial Granular Layer and Transient Versus Persisting Cajal-Retzius Neurons of the Fetal Human Cortex

Cerebral Cortex (2017)

Gundela Meyer Miriam González‐Gómez

Neurons of the subpial granular layer (SGL) in the human marginal zone (MZ) migrate tangentially from the periolfactory subventricular zone all over the neocortex. After an immature stage, from 14 to 18 gestational weeks (GW), the SGL attains maximum prominence around midgestation. At 20-25 GW, a transient miniature cell type in the MZ expresses glutamate decarboxylase (GAD) and calretinin, and extends a varicose plexus surrounding somata of large transient Cajal-Retzius neurons (tCRN), potentially modulating their activity. The compact Reelin+ horizontal axon plexus of tCRN forms a transient interface between cortical plate and MZ; it may serve as a migration substrate for cortical interneurons, and attracting NPY+ fibers from the subplate. Around 30 GW, after the disappearance of SGL and tCRN, a population of persisting Cajal-Retzius neurons (pCRN) appears and remains into adult life. pCRNs express Reelin, Tbr1, calretinin, nitric oxide synthase, and the cytokine receptor CXCR4. They are characterized by subpial location, closeness to blood vessels, and aggregation in the walls of developing sulci. Unlike tCRNs, pCRNs do not develop a compact axon plexus in the lower MZ. Occasional mitoses in the midgestation SGL suggest that CRN progenitor cells may give rise to late-appearing pCRNs populating the definitive molecular layer.

Subplate

Calretinin

Interneuron

Neocortex

10.1093/cercor/bhx110

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Developmental Expression of Neurotensin in Thyrotropes and Gonadotropes of Male and Female Rats

Neuroendocrinology (2004)

Aixa R. Bello Ricardo Reyes Guadalberto Hernández Isabel Negrín Miriam González‐Gómez

Besides its potential roles as a central neuromodulator or a hypothalamic neurohormone, neurotensin (NT) may also have endocrine function in the anterior pituitary of mammals. We previously found that NT immunoreactivity is present in the secretory granules of gonadotropes and thyrotropes in both male and female rats, where its levels of expression are under the control of sex steroids. In this work, using immunocytochemistry and in situ hybridization, we have studied the postnatal development of NT-like immunoreactivity (NTir) and the mRNA encoding NT (mRNA-NT) in specific anterior pituitary cells of both male and female rats. NT expression starts after birth and displays an identical pattern in both sexes until sexual maturity, with mRNA-NT being detected from day 2 of postnatal life in thyrotropes localized in the central portion of the anterior lobe. This pattern of expression develops progressively throughout the 2nd and 3rd weeks in both sexes. By the beginning of the 3rd week, mRNA-NT can also be detected in gonadotropes localized in the periphery of the gland coinciding with a rise in serum estradiol concentrations in both sexes, and by day 21, mRNA-NT is extensively present in both the periphery and the central region. NTir is observed from days 5–6 in thyrotropes predominantly localized in the central portion of the anterior lobe, and by day 21, NTir is also detected in gonadotropes localized in the periphery of the gland. This pattern remains similar in both sexes until the time of puberty, when female rats start displaying plastic changes in NT expression according to the stage of the estrous cycle. These findings indicate that NT expression in the rat anterior pituitary is cell specific, and develops from birth to adulthood under the control of sex steroid hormones. In addition, preliminary data showing the presence of NT receptors in rat pituitary cells support the hypothesis of a paracrine or an autocrine role for this peptide within the pituitary.

Thyrotropic cell

Corticotropic cell

10.1159/000076632

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Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis

International Journal of Molecular Sciences (2022)

Lucio Díaz‐Flores Ricardo Gutiérrez Maria Pino García Miriam González‐Gómez Lucio Díaz‐Flores

Perivascular cells in the pericytic microvasculature, pericytes and CD34+ stromal cells/telocytes (CD34+SCs/TCs), have an important role in angiogenesis. We compare the behavior of these cells depending on whether the growth of endothelial cells (ECs) from the pre-existing microvasculature is toward the interstitium with vascular bud and neovessel formation (sprouting angiogenesis) or toward the vascular lumen with intravascular pillar development and vessel division (intussusceptive angiogenesis). Detachment from the vascular wall, mobilization, proliferation, recruitment, and differentiation of pericytes and CD34+SCs/TCs, as well as associated changes in vessel permeability and functionality, and modifications of the extracellular matrix are more intense, longer lasting over time, and with a greater energy cost in sprouting angiogenesis than in intussusceptive angiogenesis, in which some of the aforementioned events do not occur or are compensated for by others (e.g., sparse EC and pericyte proliferation by cell elongation and thinning). The governing mechanisms involve cell–cell contacts (e.g., peg-and-socket junctions between pericytes and ECs), multiple autocrine and paracrine signaling molecules and pathways (e.g., vascular endothelial growth factor, platelet-derived growth factor, angiopoietins, transforming growth factor B, ephrins, semaphorins, and metalloproteinases), and other factors (e.g., hypoxia, vascular patency, and blood flow). Pericytes participate in vessel development, stabilization, maturation and regression in sprouting angiogenesis, and in interstitial tissue structure formation of the pillar core in intussusceptive angiogenesis. In sprouting angiogenesis, proliferating perivascular CD34+SCs/TCs are an important source of stromal cells during repair through granulation tissue formation and of cancer-associated fibroblasts (CAFs) in tumors. Conversely, CD34+SCs/TCs have less participation as precursor cells in intussusceptive angiogenesis. The dysfunction of these mechanisms is involved in several diseases, including neoplasms, with therapeutic implications.

Sprouting angiogenesis

Pericyte

10.3390/ijms23169010

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Aproximación al significado léxico con primitivos y moléculas: trabajo experimental (I)

María Auxiliadora Barrios Rodríguez Paula Hernádez Laynez Elena García Velázquez Ruth Mazón Irene Martín del Barrio

Documento de trabajo que recoge trece informes realizados por estudiantes del Grado de Lengua Espanola y sus Literaturas durante el curso 2017/18, que recoge los datos, su analisis y discusion de diversos trabajos experimentales en los que se intenta una aproximacion al significado lexico de algunas palabras mediante primitivos y moleculas. Este trabajo se inserta en el Proyecto de Innovacion Piensapalabras (2017/18, no 125).

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Papel de la proteína DLK1/Pref-1 en los diferentes sistemas celulares

Majorensis: Revista Electrónica de Ciencia y Tecnología (2016)

Ricardo A. Puertas Avendaño Luis García Hernández Abad Ibrahim González Marrero Ana Canerina Luis Amaro Raquel Marín Cruzado

espanolEl ligando no canonico (no clasico) de la ruta de senalizacion Notch, Delta like-1 (DLK1) se expresa durante todo el desarrollo fetal y se limita a pocos organos y/o tejidos en la edad adulta. Actualmente, DLK1 es el ligando no clasico de Notch mejor estudiado, e in vitro actua inhibiendo Notch, pero in vivo, su accion es poco clara. Niveles de expresion de Dlk1 determinan el curso de la diferenciacion y la proliferacion celular, y en tejidos como la glandula hipofisaria su expresion es necesaria para el mantenimiento de la poblacion de celulas somatotropas (GH) y la homeostasis de los diferentes ejes adenohipofisarios. Alteraciones en la ruta Delta-Notch han sido asociadas a diversos procesos fisiopatologicos tales como; Prolactinomas, carcinoma hepatico, y cancer gastrico, entre otras. Los estudios analizados en esta revision muestran tres aspectos a resaltar. Primero, que los mecanismos de senalizacion y/o regulacion Delta-Notch son cruciales en el control de la proliferacion celular y el mantenimiento indiferenciado de celulas madre. Segundo, que la impronta paterna de Dlk1 es clave para la compresion de procesos patologicos y tercero, que existe la necesidad de realizar mas estudios in vivo sobre la expresion de Dlk1, los cuales arrojarian mayor claridad en el papel de este gen. EnglishThe non-canonical (non-classical) ligand of the Notch signaling pathway, Delta like-1 (DLK1) is expressed throughout fetal development, and is limited to few organs or tissues in adulthood. Presently, DLK1 is the best studied non-classical ligand of Notch. In vitro, this gen acts inhibiting Notch whereas, in vivo, its action is unclear. The levels of DLK1 expression determine the course of cell differentiation and proliferation. In some tissues, such as the pituitary gland, DLK1 expression is required for the maintenance of the somatotropic (GH) cells population, and also for the homeostasis of the different adenohypophysial axes. Alterations in the Delta-Notch pathway have been associated with several pathophysiological processes such as, prolactinomas, hepatic carcinoma, and gastric cancer, among others. The studies discussed in this review tackle three important aspects of DLK1 regulation and function. First, that the mechanisms of signaling and/or regulation of Delta-Notch are crucial in the control of cell proliferation, and undifferentiated maintenance of stem cells. Secondly, that the paternal imprint of DLK1 is key to the compression of pathological processes and third, that there is a need for further in vivo studies on the expression of DLK1, in order to further clarify the role of this gene.

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