1,720,961 research outputs found
Mitochondrial functionality is regulated by alkylphosphocholines in human colon cancer cells
No full text[eng] Perifosine is a type of alkylphosphocholines (APCs), a group of antiproliferative drugs that inhibit the
growth of cancer cells without targeting DNA. In contrast to chemotherapeutic drugs, these lipophilic
agents are targeted to the cell membranes and induced cell death by a controversial mechanism. It has
been observed that during cancer progression there is an alteration in mitochondrial function and
oxidative stress. The aim of this study was to determine the effect of perifosine in mitochondrial
functionality and ROS production in human colon cancer cells HT29 and SW620. For this purpose, we
determined parameters of H2O2production, cardiolipin content, Δψm determination and protein levels of
OXPHOS, UCP2 and PGC-1α. Results show that perifosine caused an increase in Δψm and it is correlated
to the reduction in the UCP2 levels. Besides, the treatment produces an increase in the ROS production
and an unbalance in the proteins of respiratory chain. Biomarkers of mitochondrial biogenesis such as the
cardiolipin content and PGC-1α are increased by the treatment. In conclusion, the anticancer effect of
perifosine could be related to the deregulation of mitochondrial homeostasis in the cancer cell.[spa] La perifosina forma parte del grupo de las alquilfosfocolinas, un grupo de agentes antiproliferativos que
inhiben el crecimiento de células cancerígenas sin dañar el ADN. En contraste con otras drogas
quimioterapéuticas, estos agentes lipofílicos se insertan en las membranas celulares de la célula e inducen
la muerte celular por un mecanismo poco conocido. Durante la progresión del cáncer se ha demostrado
alteraciones en la función mitocondrial y el estrés oxidativo. El objetivo de este estudio es determinar el
efecto de la perifosina en la función mitocondrial y la producción de ROS en las líneas de cáncer de colon
humano HT29 y SW620. Por este motivo, se determinó la producción de H2O2, el contenido de
cardiolipina, el potencial de membrana y los niveles proteicos de OXPHOS, UCP2 y PGC-1α. Los resultados
muestran que la perifosina produce un aumento del potencial de membrana mitocondrial que se
relaciona con un descenso de UCP2. Además, el tratamiento incrementa la producción de ROS y produce
un desbalance en los niveles proteicos de la cadena respiratoria. Biomarcadores de biogénesis
mitocondrial como el contenido de cardiolipina y los niveles de PGC-1α aumentaron con el tratamiento.
En conclusión, parece que el efecto anticancerígeno de la perifosina podría estar relacionado con una
desregulación de la homeostasis de la mitocondria en la célula cancerígena
Estudio del estrés oxidativo inducido por citotóxicos en líneas celulares de cáncer de colon
No full text[spa] El estrés oxidativo es un factor fundamental para el desarrollo y el tratamiento del cáncer colorrectal. Se está investigando el uso de antioxidantes como la genisteína (GEN) en el tratamiento de diferentes tipos de cáncer. En este trabajo nos hemos propuesto estudiar el efecto de la GEN en concentraciones fisiológicas como coadyuvante dietético del tratamiento de líneas celulares de cáncer de colon en diferente estadio tumoral: HT29 (cáncer primario) y SW620 (cáncer metastásico). En una primera fase se ha evaluado el efecto del tratamiento con 5-FU, IRI y OXA, así como de la GEN, para determinar el fármaco más efectivo y seleccionar la dosis a probar del mismo y de la GEN. Se ha observado que hay un descenso de la viabilidad celular a medida que aumenta la concentración de fármaco que se relaciona un incremento de las especies reactivas de oxígeno (ROS). El 5-FU es más efectivo en HT29 y OXA e IRI en SW620. Se ha podido observar que la GEN junto a OXA inducen de forma sinérgica la muerte celular en las células metastásicas SW620. La suplementación con GEN no cambia el nivel de ROS producido por el OXA. Se especula por un nuevo mecanismo producido por la interacción GEN y OXA e independiente de ROS. En la línea de tumor primario HT29 no hay un efecto sinérgico de los dos fármacos.[eng] Oxidative stress is a key factor in the development and treatment of colorectal cancer. The use of antioxidants such as genistein (GEN) in the treatment of several types of cancer is being investigated. In this study we decided to determine the effect of GEN in physiologic concentrations as a dietary coadjuvant of the treatment of colon cancer cell lines in different stages of cancer: HT29 (primary tumour) and SW620 (metastatic tumour). First, the effect of the treatment with 5-FU, IRI and OXA, as well as of GEN, has been assessed in order to determine the most effective drug and choose the dose of drug and GEN to be tested. It has been observed that there is a decrease in cell viability as the concentration of the drug is increased, which is related to an increase in reactive oxygen species (ROS). 5-FU is more effective in HT29 and OXA and IRI in SW620. It has been observed that GEN along with OXA synergistically induce cell death in the metastatic line SW620. The supplementation with GEN doesn’t change the level of ROS produced by OXA. A new mechanism produced by the interaction between GEN and OXA and independent of ROS has been speculated. In the primary tumour cell line HT29 there is not a synergistic effect of the two drugs
Rank signaling pathway: from mammary gland biology to neuroendocrine regulation of reproduction
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 23-05-2025Esta Tesis tiene embargado el acceso al texto completo hasta el 23-11-2026La vía de señalización de Rank regula la homeostasis de la glándula mamaria y la diferenciación de las células epiteliales. Aunque Rank se expresa en las células basales y luminales de la mama, su papel en cada linaje celular está por esclarecer. Al combinar la deleción genética de Rank exclusivamente en células luminales y técnicas de trazado de linaje, observamos que la señalización de Rank es esencial para mantener el reservorio de células madre luminales y reprime un mecanismo de diferenciación alveolar prematuro en la glándula mamaria. Además, la señalización de Rank en las células luminales media los efectos proliferativos de la progesterona y la prolactina, y su deficiencia provoca una alveologénesis y lactogénesis defectuosa durante el primer embarazo. La lactancia se recupera en el siguiente embarazo mediante la activación de la bipotencia de las células basales, donde la vía de Rank media su diferenciación a luminales permitiendo la recuperación de la capacidad de producir leche.
Por otro lado, la señalización de Rank controla el desarrollo de la glándula mamaria de forma sistémica, a través de un mecanismo independiente del epitelio mamario: la activación del eje hipotalámico-pituitario-gonadal. Rank es importante en la activación de este eje y media la maduración sexual y, por tanto, el desarrollo mamario durante la pubertad. Se han identificado mutaciones en RANK en pacientes con hipogonadismo hipogonadotrópico congénito, lo que indica su importancia en humanos. La señalización de Rank en la microglía del hipotálamo regula la función de las neuronas GnRH, activando el eje pituitario-gonadal tanto en ratones macho como en hembras. Análisis transcriptómicos de células individuales han revelado tres subpoblaciones de microglía hipotalámica, predominantemente en un estado activado, asociadas con la población de la eminencia media, donde Rank regula la subpoblación más activa. La deleción de Rank altera la morfología y actividad de la microglía en la eminencia media del hipotálamo, donde se secreta GnRH.
En su conjunto, estos hallazgos destacan la importancia de la señalización de Rank tanto en el desarrollo de la glándula mamaria como en la regulación neuroendocrina de la reproducció
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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