Search results for "Essentiality"
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Essentiality Is a Strong Determinant of Protein Rates of Evolution during Mutation Accumulation Experiments in Escherichia coli
2016
[EN] The Neutral Theory of Molecular Evolution is considered the most powerful theory to understand the evolutionary behavior of proteins. One of the main predictions of this theory is that essential proteins should evolve slower than dispensable ones owing to increased selective constraints. Comparison of genomes of different species, however, has revealed only small differences between the rates of evolution ofessential and nonessential proteins. In some analyses, these differences vanish once confounding factors are controlled for, whereas in other cases essentiality seems to have an independent, albeit small, effect. It has been argued that comparing relatively distant genomes may entai…
Drivers of topoisomerase II poisoning mimic and complement cytotoxicity in AML cells
2019
Recently approved cancer drugs remain out-of-reach to most patients due to prohibitive costs and only few produce clinically meaningful benefits. An untapped alternative is to enhance the efficacy and safety of existing cancer drugs. We hypothesized that the response to topoisomerase II poisons, a very successful group of cancer drugs, can be improved by considering treatment-associated transcript levels. To this end, we analyzed transcriptomes from Acute Myeloid Leukemia (AML) cell lines treated with the topoisomerase II poison etoposide. Using complementary criteria of co-regulation within networks and of essentiality for cell survival, we identified and functionally confirmed 11 druggabl…
Characterization of the metabolic profile and identification of potential therapeutic targets in advanced prostate cancer patients
2023
INTRODUCCIÓN El cáncer de próstata (CaP) representa el segundo tumor en incidencia en hombres y es la quinta causa de muerte por cáncer a nivel global. El CaP es un tumor hormono-dependiente, que requiere de la activación del receptor de andrógenos (AR) para su proliferación. Clínicamente, se caracteriza por una gran variabilidad en su evolución, progresando desde una condición indolente hasta un fenotipo agresivo que puede diseminarse y metastatizar a los nodos linfáticos y huesos. Actualmente, el diagnóstico temprano del CaP se realiza mediante la determinación sérica del antígeno prostático específico (PSA) y el examen rectal digital (DRE). Si estas pruebas dan resultados anómalos y hay …