445 research outputs found
NF-kB and Disease
No full textThe role of NF-κB in all diseases characterized by an inflammatory process, from cancer to autoimmune diseases, is known, but—precisely because it is involved in many diseases—this transcriptional factor continues to attract scientific research and the new knowledge that emerges is fundamental in highlighting the therapeutic potential that this factor can have in the various diseases in which it is involved [...
Eduardo Lourenço: Amigo dos poetas
No full textEntrevista com Eduardo Lourenço no dia 5 julho 2018 - referente ao lançamento de Fernando Pessoa Revisitado, Brasil /Editora Tinta da China - realizada pela Professora Doutora Paola Poma da Universidade de São Paulo e pelo Professor Doutor Fernando Ribeiro da Universidade Nova de Lisboa na Fundação Calouste Gulbenkian, em Lisboa
Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View
No full textMultidrug resistance (MDR), of the innate and acquired types, is one of major problems in treating tumor diseases with a good chance of success. In this review, we examine the key role of nuclear factor-kappa B (NF-κB) to induce MDR in three tumor models characterized precisely by innate or acquired MDR, in particular triple negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and acute myeloid leukemia (AML). We also present different pharmacological approaches that our group have employed to reduce the expression/activation of this transcriptional factor and thus to restore chemo-sensitivity. Finally, we examine the latest scientific evidence found by other groups, the most significant clinical trials regarding NF-κB, and new perspectives on the possibility to consider this transcriptional factor a valid drug target in neoplastic diseases
Natural Inhibitors of P-glycoprotein in Acute Myeloid Leukemia
No full textAcute myeloid leukemia (AML) remains an insidious neoplasm due to the percentage of patients who develop resistance to both classic chemotherapy and emerging drugs. Multidrug resistance (MDR) is a complex process determined by multiple mechanisms, and it is often caused by the overexpression of efflux pumps, the most important of which is P-glycoprotein (P-gp). This mini-review aims to examine the advantages of using natural substances as P-gp inhibitors, focusing on four molecules: phytol, curcumin, lupeol, and heptacosane, and their mechanism of action in AML
Patterns of Innate or Acquired Resistance to Anticancer Drugs: Our Experience to Overcome It
No full textDrug resistance, which is often of a multiple type, can be defined as the ability of cancer cells to obtain resistance to both conventional and novel chemotherapy agents. It remains a major problem to solve in cancer therapy. The mechanisms of resistance are multifactorial, and in our cellular models of acute myeloid leukemia, hepatocellular carcinoma, and triple-negative breast cancer, it involves the NF-κB pathway. In our opinion, multitarget molecules can be considered as privileged compounds capable of attacking and reversing the resistant phenotype. In the phenomena of both innate and acquired drug resistance that we have been studying since 1998 to today and up to 2016 under the guidance of Professor Natale D’Alessandro, more strictly pharmacological factors are certainly involved. These factors include P-glycoprotein and biological factors such as inhibitory proteins; apoptosis; the Raf-1 kinase inhibitor protein, an important tumor suppressor and metastasis inhibitor, which enhances drug-induced apoptosis of cancer cells; and Yin Yang, a transcription factor involved in drug resistance
Tasso nelle Annotazioni leopardiane
No full textNel lavoro di documentazione che Leopardi svolge dal 1822 al 1824 per certificare l'origine letteraria della propria nuova lingua poetica, ha un posto di particolare preminenza la lingua di Tasso, che si rivela un autore particolarmente congeniale al poeta, non solo per ragioni biografiche, ma anche strettamente linguistiche, come mostrano le note autografe apposte sul manoscritto della Annotazioni, la cui edizione critica, procurata da Paola Italia nel 2006, è interpretata e studiata nel contesto critico letterario della formazione del libro delle Canzoni del 1824.In the work of documentation that Leopardi plays from 1822 to 1824 to certify the origin of their new literary poetic language, has a place of special prominence the language of Tasso, the author reveals a particularly congenial to the poet, not only for biographical reasons, strictly linguistic but also, as shown by the notes affixed to the autograph manuscript of the Notes, whose critical edition, procured by Paola Italy in 2006, is interpreted and studied in the context of the formation of the literary critic of the book Songs of 1824
Características del control interno de inventarios de la pequeña empresa “GRUPO PAOLA” SRL de Huaraz, 2015
No full textEl presente trabajo tuvo el siguiente enunciado del problema, ¿Cuáles son las características del control interno de inventarios de la pequeña empresa “Grupo Paola” SRL de Huaraz 2015? así también se consideró como objetivo general, Determinar las características del control interno de inventarios de la pequeña empresa “Grupo Paola” SRL de Huaraz 2015. La metodología de la investigación empleada fue descriptiva, según Hernández, Fernández y Baptista (2010), nos dice que en este tipo de investigación se utiliza en vez de la hipótesis, la recolección y análisis de los datos sin medición numérica los cuales ayuda a descubrir o afinar preguntas de investigación en el proceso de interpretación, se consideró como población y muestra a la empresa “Grupo Paola” SRL , integrada por 12 trabajadores encargados del área de inventarios y movimientos de almacén. Para la técnica se utilizó la encuesta y el instrumento utilizado fue el cuestionario. Se llegó a los siguientes resultados, que se planifica la implementación de los instrumentos de control de los inventarios, el 75% de los encuestados señala que si se establecen los instrumentos de control; considerando la importancia de este sistema de control, planificándose adecuadamente el manejo de inventarios, como el 75% de los encuestados, lo manifiesta, el cual permitirá una atinada gestión. Finalmente, se llegó a la siguiente conclusión de que si existe un control interno de inventarios adecuado según las encuestas realizadas. Y de la misma manera se concluye que se pudo describir las características del control interno de inventarios.Tesi
Antitumor Effect of Glandora rosmarinifolia (Boraginaceae) Essential Oil through Inhibition of the Activity of the Topo II Enzyme in Acute Myeloid Leukemia
No full textIt was previously shown that the antitumor and cytotoxic activity of the essential oil (EO) extracted from the aerial parts of Glandora rosmarinifolia appears to involve a pro-oxidant mechanism in hepatocellular carcinoma (HCC) and in triple-negative breast cancer (TNBC) cell lines. Its most abundant compound is a hydroxy-methyl-naphthoquinone isomer. Important pharmacological activities, such as antitumor, antibacterial, antifungal, antiviral and antiparasitic activities, are attributed to naphthoquinones, probably due to their pro-oxidant or electrophilic potential; for some naphthoquinones, a mechanism of action of topoisomerase inhibition has been reported, in which they appear to act both as catalytic inhibitors and as topoisomerase II poisons. Our aim was to evaluate the cytotoxic activity of the essential oil on an acute myeloid leukemia cell line HL-60 and on its multidrug-resistant (MDR) variant HL-60R and verify its ability to interfere with topoisomerase II activity. MTS assay showed that G. rosmarinifolia EO induced a decrease in tumor cell viability equivalent in the two cell lines; this antitumor effect could depend on the pro-oxidant activity of EO in both cell lines. Furthermore, G. rosmarinifolia EO reduced the activity of Topo II in the nuclear extracts of HL-60 and HL-60R cells, as inferred from the inability to convert the kinetoplast DNA into the decatenated form and then not inducing linear kDNA. Confirming this result, flow cytometric analysis proved that EO induced a G(0)-G(1) phase arrest, with cell reduction in the S-phase. In addition, the combination of EO with etoposide showed a good potentiation effect in terms of cytotoxicity in both cell lines. Our results highlight the antitumor activity of EO in the HL-60 cell line and its MDR variant with a peculiar mechanism as a Topo II modulator. Unlike etoposide, EO does not cause stabilization of a covalent Topo II-DNA intermediate but acts as a catalytic inhibitor. These data make G. rosmarinifolia EO a potential anticancer drug candidate due to its cytotoxic action, which is not affected by multidrug resistance
Conflicto colonial andino y mediación teológica en la crónica de Guamán Poma
No full textLa Nueva corónica y buen gobierno de Felipe Guamán Poma de Ayala representa un documento de protesta muy singular en palabras e imágenes, como defensa de los indígenas maltratados y explotados por el sistema colonial. El cronista como indígena cristiano critica a los funcionarios políticos y religiosos de la colonia, posición que no implica necesariamente la ruptura con el sistema colonial. Para Guamán Poma, lo que amenaza la vida de las culturas indígenas no es la predicación de la salvación ni la forma ideal de vida cristiana, sino las concreciones históricas con las que el cristianismo es transmitido en la Colonia. La mediación teológica que plantea el cronista la formula desde la pregunta por la ruptura y continuidad, por la compatibilidad e incompatibilidad que se presenta entre las religiones andinas y el cristianismo.La nueva corónica y buen gobierno by Felipe Guamán Poma de Ayala represents a document of protest outstanding in words and images for the defense of the oppressed natives. The writer’s own experience as native and Christian is the startingpoint for his citizism of the colonial system. In his opinion the negative influence on the native culture wasn’t caused by the Christian promise of salvation nor by the proclaimed ideal way of Christian living, but by the way Christianity was transformed through the colonial context. The author´s main interest is to raise the question of the interruption and continuance and the compatibility and incompatibility between the native religions and Christianity
Análises Iconográficas da Obra de Felipe Guamán Poma de Ayala
No full textThrough the analysis of some images from the book La nueva corónica y buen gobierno by Felipe Guamán Poma de Ayala, the article aims to investigate the representations of Spaniards and indigenous people made by a Peruvian author between the 16th and 17th centuries.A través del análisis de algunas imágenes del libro La nueva corónica y buen gobierno de Felipe Guamán Poma de Ayala, el artículo pretende investigar las representaciones de españoles e indígenas realizadas por un autor peruano en el siglo comprendido entre los siglos XVI y XVII.Através da análise de algumas imagens do livro La nueva corónica y buen gobierno de Felipe Guamán Poma de Ayala, o artigo tem como intuito investigar as representações de espanhóis e indígenas feitas por um autor peruano no século entre os séculos XVI e XVII
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