α-Hispanolol Induces Apoptosis and Suppresses Migration and Invasion of Glioblastoma Cells Likely via Downregulation of MMP-2/9 Expression and p38MAPK Attenuation

α-Hispanolol (α-H) is a labdane diterpenoid that has been shown to induce apoptosis in several human cancer cells. However, the effect of α-H in human glioblastoma cells has not been described. In the present work, we have investigated the effects of α-H on apoptosis, migration, and invasion of human glioblastoma cells with the aim of identifying the molecular targets underlying its mechanism of action. The results revealed that α-H showed significant cytotoxicity against human glioma cancer cell lines U87 and U373 in a concentration- and time-dependent manner. This effect was higher in U87 cells and linked to apoptosis, as revealed the increased percentage of sub-G1 population by cell cycle analysis and acquisition of typical features of apoptotic cell morphology. Apoptosis was also confirmed by significant presence of annexin V-positive cells and caspase activation. Pretreatment with caspase inhibitors diminishes the activities of caspase 8, 9, and 3 and maintains the percentage of viable glioblastoma cells, indicating that α-H induced cell apoptosis through both the extrinsic and the intrinsic pathways. Moreover, we also found that α-H downregulated the anti-apoptotic Bcl-2 and Bcl-xL proteins and activated the pro-apoptotic Bid and Bax proteins. On the other hand, α-H exhibited inhibitory effects on the migration and invasion of U87 cells in a concentration-dependent manner. Furthermore, additional experiments showed that α-H treatment reduced the enzymatic activities and protein levels of matrix metalloproteinase MMP-2 and MMP-9 and increased the expression of TIMP-1 inhibitor, probably via p38MAPK regulation. Finally, xenograft assays confirmed the anti-glioma efficacy of α-H. Taken together, these findings suggest that α-H may exert anti-tumoral effects in vitro and in vivo through the inhibition of cell proliferation and invasion as well as by the induction of apoptosis in human glioblastoma cells. This research describes α-H as a new drug that may improve the therapeutic efficacy against glioblastoma tumors.This study was supported by grant PI11/00036, PI14/00055, and PI17/00012 from the FIS, MPY 1410/09 from ISCIII and Spanish Ministry of Health (Instituto de Salud Carlos III; RD12/0036/0059) to SoH and by grants IERPY 1149/16 and IERPY-M 389/18 to AL. L JG was supported by FIS (FI12/00340). SaH was supported by IERPY 1149/16 from ISCIII.S

Paradigmas tecnocientíficos en el campo del arte : Relaciones transdisciplinares entre lenguajes naturales y formales

Las producciones artísticas desde 1960 a la fecha han trabajado conceptual o directamente con un lenguaje, regla, código, o instrucción que hace posible y visible, activa y dinámicamente las obras. Desde las investigaciones sobre la Cibernética, la Teoría de los Sistemas, la Inteligencia Artificial, la relación humano/máquina, el concepto de Interfaz y concretamente los diferentes lenguajes de programación han sido desde hace 3 o 4 décadas material de investigación y producción artística desarrollada en ámbitos académicos, difundida en Universidades, laboratorios, revistas y escuelas especializadas, y apoyada económicamente por gobiernos, instituciones y fundaciones estatales o privadas. Actualmente el campo que estamos investigando está orientado a que los lenguajes formales anti-intuitivos se acerquen a la posibilid ad de trabajar con lenguajes naturales y artificiales. (Párrafo extraído del texto a modo de resumen) Mesa: Nuevas tecnologías, nuevos abordajesFacultad de Bellas Arte

Paradigmas tecnocientíficos en el campo del arte : Relaciones transdisciplinares entre lenguajes naturales y formales

Las producciones artísticas desde 1960 a la fecha han trabajado conceptual o directamente con un lenguaje, regla, código, o instrucción que hace posible y visible, activa y dinámicamente las obras. Desde las investigaciones sobre la Cibernética, la Teoría de los Sistemas, la Inteligencia Artificial, la relación humano/máquina, el concepto de Interfaz y concretamente los diferentes lenguajes de programación han sido desde hace 3 o 4 décadas material de investigación y producción artística desarrollada en ámbitos académicos, difundida en Universidades, laboratorios, revistas y escuelas especializadas, y apoyada económicamente por gobiernos, instituciones y fundaciones estatales o privadas. Actualmente el campo que estamos investigando está orientado a que los lenguajes formales anti-intuitivos se acerquen a la posibilid ad de trabajar con lenguajes naturales y artificiales. (Párrafo extraído del texto a modo de resumen) Mesa: Nuevas tecnologías, nuevos abordajesFacultad de Bellas Arte

Paradigmas tecnocientíficos en el campo del arte : Relaciones transdisciplinares entre lenguajes naturales y formales

Las producciones artísticas desde 1960 a la fecha han trabajado conceptual o directamente con un lenguaje, regla, código, o instrucción que hace posible y visible, activa y dinámicamente las obras. Desde las investigaciones sobre la Cibernética, la Teoría de los Sistemas, la Inteligencia Artificial, la relación humano/máquina, el concepto de Interfaz y concretamente los diferentes lenguajes de programación han sido desde hace 3 o 4 décadas material de investigación y producción artística desarrollada en ámbitos académicos, difundida en Universidades, laboratorios, revistas y escuelas especializadas, y apoyada económicamente por gobiernos, instituciones y fundaciones estatales o privadas. Actualmente el campo que estamos investigando está orientado a que los lenguajes formales anti-intuitivos se acerquen a la posibilid ad de trabajar con lenguajes naturales y artificiales. (Párrafo extraído del texto a modo de resumen) Mesa: Nuevas tecnologías, nuevos abordajesFacultad de Bellas Arte

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas

Background and objectives: Bexarotene has been approved to treat advanced stage cutaneous T -cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. Material and method: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or S & eacute;zary syndrome (42) on a 10 -year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. Results: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27 - 95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1 - 114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment -related grade 5 adverse events were reported. Conclusions: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL. (c) 2024 AEDV. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil

<p>Abstract</p> <p>Background</p> <p>Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H⁺-ATPase (β-F1-ATPase). The <it>bioenergetic signature </it>is a protein ratio (β-F1-ATPase/GAPDH), which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the <it>bioenergetic signature </it>of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP) and iodoacetate (IA), and the anti-metabolite, 5-fluorouracil (5-FU).</p> <p>Methods</p> <p>The <it>bioenergetic signature </it>of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the <it>bioenergetic signature </it>and the cell death response. <it>In vivo </it>tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells.</p> <p>Results</p> <p>We demonstrate that the <it>bioenergetic signature </it>of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the <it>bioenergetic signature </it>directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the <it>in vitro </it>cell-death responses associated with 3BrP, IA and 5-FU, the <it>in vivo </it>tumor regression activities of these agents were comparable.</p> <p>Conclusions</p> <p>Overall, we suggest that the determination of the <it>bioenergetic signature </it>of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression.</p

Night shift work and stomach cancer risk in the MCC-Spain study

OBJECTIVES: Night shift work has been classified as a probable human carcinogen by the International Agency for Research on Cancer, based on experimental studies and limited evidence on human breast cancer risk. Evidence at other cancer sites is scarce. We evaluated the association between night shift work and stomach cancer risk in a population-based case-control study. METHODS: A total of 374 incident stomach adenocarcinoma cases and 2481 population controls were included from the MCC-Spain study. Detailed data on lifetime night shift work were collected including permanent and rotating shifts, and their cumulative duration (years). Adjusted unconditional logistic regression models were used in analysis. RESULTS: A total of 25.7% of cases and 22.5% of controls reported ever being a night shift worker. There was a weak positive, non-significant association between ever having had worked for at least 1?year in permanent night shifts and stomach cancer risk compared to never having worked night shifts (OR=1.2, 95% CI 0.9 to 1.8). However, there was an inverse 'U' shaped relationship with cumulative duration of permanent night shifts, with the highest risk observed in the intermediate duration category (OR 10-20?years=2.0, 95% CI 1.1 to 3.6) (p for trend=0.19). There was no association with ever having had worked in rotating night shifts (OR=0.9, 95% CI 0.6 to 1.2) and no trend according to cumulative duration (p for trend=0.68). CONCLUSION: We found no clear evidence concerning an association between night shift work and stomach cancer ris

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Diseño de una red de banda ancha para cubrir las necesidades de transferencia de información del mercado ecuatoriano

Comenzamos este estudio estableciendo las bases teóricas sobre las redes de banda ancha . Estudiamos los protocolos de transmisión y trasporte utilizados en estas redes como son : X.25, Frame Relay, ATM , SDH y DWDM . Además de esto todas las características de la fibra óptica que es el medio de transmisión que ha hecho posible el desarrollo de la banda ancha Continuamos con un análisis de mercado mediante el cual seleccionamos las ciudades a las que se le brindará servicio. Una vez que hemos seleccionado las ciudades procedemos a realizar los respectivos cálculos para dimensionar los anillos que conformarán la red. Escogeremos los equipos que soporten estas velocidades de transmisión; realizamos un análisis de costos involucrados en la puesta en marcha y funcionamiento de nuestra red . Además de esto realizamos un estudio de los aspectos legales que debemos tener en cuenta para la implementación y puesta en marcha de nuestra red de banda ancha. Concluimos nuestro estudio con una comparación técnico económica con otros medios de trasmisión. Introducción El presente trabajo tiene como objetivo establecer la base para una futura implementación de una red de banda ancha que abarque todos los mercados de nuestro país , ya que actualmente no existen estudios que satisfagan los requerimientos de transferencia de información entre ciudades , con tecnología de banda ancha y que brinden una solución compacta y completa