551 research outputs found
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Neoplastic cells are a rare component in human glioblastoma microvasculature
Microvascular proliferation is a key biological and diagnostic hallmark of human glioblastoma, one of the most aggressive forms of human cancer. It has recently been suggested that stem-like glioblastoma cells have the capacity to differentiate into functional endothelial cells, and that a significant proportion of the vascular lining in tumors has a neoplastic origin. In principle, this finding could significantly impact the efficacy and development of antiangiogenic therapies targeting the vasculature. While the potential of stem-like cancer cells to form endothelium in culture seems clear, in our clinical experience using a variety of molecular markers, neoplastic cells do not contribute significantly to the endothelial-lined vasculature of primary human glioblastoma. We sought to confirm this impression by analyzing vessels in glioblastoma previously examined using chromogenic in situ hybridization (CISH) for EGFR and immunohistochemistry for mutant IDH1. Vessels containing cells expressing these definitive neoplastic markers were identified in a small fraction of tumors, but only 10% of vessel profiles examined contained such cells and when identified these cells comprised less than 10% of the vascular cellularity in the cross section. Interestingly, these rare intravascular cells showing EGFR amplification by CISH or mutant IDH1 protein by immunohistochemistry were located in the middle or outer portions of vessel walls, but not amongst the morphologic boundaries of the endothelial lining. To more directly address the capacity of glioblastoma cells to contribute to the vascular endothelium, we performed double labeling (Immunofluorescence/FISH) for the endothelial marker CD34 and EGFR gene locus. Although rare CD34 positive neoplastic cells unassociated with vessels were identified (<1%), this analysis did not identify EGFR amplified cells within vascular linings, and further supports our observations that incorporation of glioblastoma cells into the tumor vessels is at best extremely rare, and therefore of questionable clinical or therapeutic significance
Crecimiento urbano e impacto en el ruido ambiental de la delegación Azcapotzalco. Un análisis cartográfico
El ruido ambiental en las grandes ciudades es hoy motivo de preocupaciĂłn, debido a que afecta de manera importante a la poblaciĂłn en general. La gran cantidad de actividades que dĂa a dĂa se llevan a cabo en ellas, trae consigo el uso de tecnologĂas que a su vez generan niveles importantes de ruido. El ruido por tráfico vehicular es el que mayor presencia tiene en las ciudades, ya que este es constante y la tendencia al crecimiento de vialidades y nĂşmero de vehĂculos tambiĂ©n lo es. El crecimiento urbano a lo largo del tiempo ha ido vinculado con el crecimiento del uso de tecnologĂas que buscan aliviar o facilitar la vida de los ciudadanos, y el trafico vehicular está implicito en este tipo de acciones. El desarrollo de la ciudad de MĂ©xico ha sido muy constrastante entre finales del siglo XIX y principios del siglo XXI y el impacto que este hecho ha tenido en la presencia del ruido ambiental en ella es notable. En este trabajo se realiza un estudio de este hecho a travĂ©s de la comparaciĂłn de la evoluciĂłn urbana en mapas histĂłricos de la DelegaciĂłn Azcapotzalco en cinco Ă©pocas: 1899, 1929, 1942, 1973 y 2010, y de la construcciĂłn de mapas de ruido de la demarcaciĂłn.The environmental noise we find in the big cities are a matter of concern now at days. It a ffects the city’s population in a very important way. The amounts of activities that are done in these cities each day bring with them the use of technologies that generate great levels of noise. The noise caused by the vehicular trafic is the one with more importance in the city, since it’s continuous and there is a growth in the number of vehicles every day. The urban growth within time has been linked to the increase in the use of technologies that aim to relieve and make citizens life easier and vehicular trafic is implicit in this type of actions. The development of Mexico City has been very contrasting between the end of the XIX century and beginning of the XXI. The impact that this development has had in terms of environmental noise is noticeable. In this essay we make a study about this fact through the comparison of the urban evolution in historical maps of “Azcapotzalco’s” Delegation during ve years: 1899, 1929, 1942, 1973 and 2010, and the creation of noise and demarcation maps
Misregulated E-Cadherin Expression Associated with an Aggressive Brain Tumor Phenotype
BACKGROUND: Cadherins are essential components of the adherens junction complexes that mediate cell-cell adhesion and regulate cell motility. During tissue morphogenesis, changes in cadherin expression (known as cadherin switching) are a common mechanism for altering cell fate. Cadherin switching is also common during epithelial tumor progression, where it is thought to promote tumor invasion and metastasis. E-cadherin is the predominant cadherin expressed in epithelial tissues, but its expression is very limited in normal brain. METHODOLOGY/PRINCIPAL FINDINGS: We identified E-cadherin expression in a retrospective series of glioblastomas exhibiting epithelial or pseudoepithelial differentiation. Unlike in epithelial tissues, E-cadherin expression in gliomas correlated with an unfavorable clinical outcome. Western blotting of two panels of human GBM cell lines propagated either as xenografts in nude mice or grown under conventional cell culture conditions confirmed that E-cadherin expression is rare. However, a small number of xenograft lines did express E-cadherin, its expression correlating with increased invasiveness when the cells were implanted orthotopically in mouse brain. In the conventionally cultured SF767 glioma cell line, E-cadherin expression was localized throughout the plasma membrane rather than being restricted to areas of cell-cell contact. ShRNA knockdown of E-cadherin in these cells resulted in decreased proliferation and migration in vitro. CONCLUSIONS/SIGNIFICANCE: Our data shows an unexpected correlation between the abnormal expression of E-cadherin in a subset of GBM tumor cells and the growth and migration of this aggressive brain tumor subtype
Stem cell modeling of nervous system tumors
Nervous system tumors, particularly brain tumors, represent the most common tumors in children and one of the most lethal tumors in adults. Despite decades of research, there are few effective therapies for these cancers. Although human nervous system tumor cells and genetically engineered mouse models have served as excellent platforms for drug discovery and preclinical testing, they have limitations with respect to accurately recapitulating important aspects of the pathobiology of spontaneously arising human tumors. For this reason, attention has turned to the deployment of human stem cell engineering involving human embryonic or induced pluripotent stem cells, in which genetic alterations associated with nervous system cancers can be introduced. These stem cells can be used to create self-assembling three-dimensional cerebral organoids that preserve key features of the developing human brain. Moreover, stem cell-engineered lines are amenable to xenotransplantation into mice as a platform to investigate the tumor cell of origin, discover cancer evolutionary trajectories and identify therapeutic vulnerabilities. In this article, we review the current state of human stem cell models of nervous system tumors, discuss their advantages and disadvantages, and provide consensus recommendations for future research
Estudio sobre la invisibilización de la mujer en el entorno virtual de la Universidad de Málaga
Se hace un recorrido por diversas páginas webs del entorno virtual de la Universidad de Málaga donde se puede comprobar que aunque hay algunos ápices a la hora de utilizar un lenguaje inclusivo, aun queda mucho por hacer en este tema para que realmente el lenguaje sea una representaciĂłn fiel de la realidad que vivimos las trabajadoras de esta instituciĂłn y de otras, ya que es una tĂłnica general en la gran mayorĂa de las universidades que hemos analizadoUniversidad de Málaga. Campus de Excelencia Internacional AndalucĂa Tech
Desarrollo sustentable y regenerativo de los paisajes socioecolĂłgicos de montaña: MontologĂa del Chimborazo como referente insigne del cambio global
Analizamos el predicamento del desarrollo sustentable y regenerativo enmarcado en la experiencia globalizante del cambio global, con la gran aceleraciĂłn de las Ăşltimas dĂ©cadas. Con el fin de plantear opciones prácticas de adaptaciĂłn al cambio climático y de incrementar la resiliencia, se presenta el caso del Chimborazo como referente global para incorporar la transdisciplinariedad de la montologĂa, presentada como la ciencia convergente de las montañas, consideradas como hĂbridos de naturaleza y cultura. En la Reserva de ProducciĂłn FaunĂstica de Chimborazo, los objetivos de conservaciĂłn y las prácticas de manejo del área protegida se han ceñido a los paradigmas antiguos de naturaleza prĂstina, en vez de reflejar la realidad de un sistema socioecolĂłgico productivo de data ancestral. Presentamos argumentos para reformular el status quo con la noĂ©tica y la consiliencia de los nuevos paradigmas inclusivos, como la historicidad, la transgresividad y la referencialidad del estudio de montañas. AsĂ reclamamos la necesidad de asignar al paisaje montano del Chimborazo con una nueva categorĂa; sea geoparque, reserva de la biosfera o sitio mundial de patrimonio mixto (natural y cultural)
Desarrollo sustentable y regenerativo de los paisajes socioecolĂłgicos de montaña: MontologĂa del Chimborazo como referente insigne del cambio global
Analizamos el predicamento del desarrollo sustentable y regenerativo enmarcado en la experiencia globalizante del cambio global, con la gran aceleraciĂłn de las Ăşltimas dĂ©cadas. Con el fin de plantear opciones prácticas de adaptaciĂłn al cambio climático y de incrementar la resiliencia, se presenta el caso del Chimborazo como referente global para incorporar la transdisciplinariedad de la montologĂa, presentada como la ciencia convergente de las montañas, consideradas como hĂbridos de naturaleza y cultura. En la Reserva de ProducciĂłn FaunĂstica de Chimborazo, los objetivos de conservaciĂłn y las prácticas de manejo del área protegida se han ceñido a los paradigmas antiguos de naturaleza prĂstina, en vez de reflejar la realidad de un sistema socioecolĂłgico productivo de data ancestral. Presentamos argumentos para reformular el status quo con la noĂ©tica y la consiliencia de los nuevos paradigmas inclusivos, como la historicidad, la transgresividad y la referencialidad del estudio de montañas. AsĂ reclamamos la necesidad de asignar al paisaje montano del Chimborazo con una nueva categorĂa; sea geoparque, reserva de la biosfera o sitio mundial de patrimonio mixto (natural y cultural)
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The impact of histopathology and NAB2-STAT6 fusion subtype in classification and grading of meningeal solitary fibrous tumor/hemangiopericytoma.
Meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor with propensity for recurrence and metastasis. Although multiple classification schemes have been proposed, optimal risk stratification remains unclear, and the prognostic impact of fusion status is uncertain. We compared the 2016 WHO CNS tumor grading scheme (CNS-G), a three-tier system based on histopathologic phenotype and mitotic count, to the 2013 WHO soft-tissue counterpart (ST-G), a two-tier system based on mitotic count alone, in a cohort of 133 patients [59 female, 74 male; mean age 54 years (range 20-87)] with meningeal SFT/HPC. Tumors were pathologically confirmed through review of the first tumor resection (n = 97), local recurrence (n = 35), or distant metastasis (n = 1). A STAT6 immunostain showed nuclear expression in 132 cases. NAB2-STAT6 fusion was detected in 99 of 111 successfully tested tumors (89%) including the single STAT6 immunonegative tumor. Tumors were classified by CNS-G as grade 1 (n = 43), 2 (n = 41), or 3 (n = 49), and by ST-G as SFT (n = 84) or malignant SFT (n = 49). Necrosis was present in 16 cases (12%). On follow-up, 42 patients had at least one subsequent recurrence or metastasis (7 metastasis only, 33 recurrence only, 2 patients had both). Twenty-nine patients died. On univariate analysis, necrosis (p = 0.002), CNS-G (p = 0.01), and ST-G (p = 0.004) were associated with recurrence-free (RFS) but not overall survival (OS). NAB2-STAT6 fusion type was not significantly associated with RFS or OS, but was associated with phenotype. A modified ST-G incorporating necrosis showed higher correlation with RFS (p = 0.0006) and remained significant (p = 0.02) when considering only the primary tumors. From our data, mitotic rate and necrosis appear to stratify this family of tumors most accurately and could be incorporated in a future grading scheme
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