Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails.
Abstract• Primary forests in the seasonally dry tropical regions of Mexico are disappearing under land-use pressure, creating a mosaic of secondary forests of different ages.• In this study we measured the aboveground litterfall phosphorus (P) fluxes, litter-layer and soil P pools to compare the P cycles in primary and secondary seasonally dry tropical forests. Our hypothesis was that the previous agricultural land use of secondary forests would bring about a lower P flux in the litterfall, lower soil P pool, and higher nutrient resorption proficiency than in primary forests, as well as an increase of relative amounts of available P provided by the soil with forest aging.• The expected litterfall P flux increase in the secondary forest following a previous agricultural land use did not occur. Phosphorus return to the soil by aboveground litterfall was unaffected by the succession stage of the forest. In addition, the total soil P pool did not change with forest age. However, available soil P (bicarbonate P-inorganic and P-organic pools) and hydroxide inorganic P pools were higher in primary than in secondary forest soils. Phosphorus concentration in litterfall increased significantly with forest age, suggesting that P is cycled more efficiently (by a higher nutrient resorption proficiency) when soil available P is less abundant. Despite these differences among forests, the results of our study gave evidence that P requirements by plants in primary and secondary forests are sufficiently met by the accumulation of dissolved (water extractable) P in the forest floor during the dry season and by soil bicarbonate-P pools.• Our study on the effects of land cover change on P cycling, following the discontinuation of agricultural practices, leads to the conclusion that this ecosystem P dynamics will vary depending on the successional stage of the forests, and is strongly influenced by the seasonal rainfall pattern which determines plant-available P. Mots-clés :litière / succession secondaire / disponibilité du phosphore / sols tropicaux Résumé -Cycle du phosphore dans les forêts primaires et secondaires tropicales à saison sèche du Mexique.• Les forêts primaires dans les régions tropicales à saison sèche du Mexique sont en train de disparaître sous la pression de l'utilisation agricole des terres, créant une mosaïque de forêts secondaires d'âges différents.• Dans cette étude, nous avons mesuré les flux de phosphore (P) de la litière au-dessus du sol, de l'horizon de litière et les pools de phosphore P du sol, pour comparer les cycles de P dans les forêts primaires et secondaires tropicales à saison sèche. Notre hypothèse est que l'exploitation agricole précédente des forêts secondaires devrait aboutir à un flux plus faible de P dans la litière, à un plus faible pool de P du sol, et à une résorption plus élevée des éléments nutritifs que dans les forêts primaires, ainsi qu'une augmentation des quantités relatives de P disponibles fournies par le sol avec le vieillissement de la forêt.• L'accroissement attendu du flux de ...
Cellular differentiation is a highly complex process and we need a deeper understanding of their mechanisms. Reprogramming somatic cells follows the inverse order to the physiologic differentiation process. Reprogramming somatic cells may be used as a simplistic model to understand the cellular differentiation process. The generation of induced pluripotent stem cells (iPSCs) requires going along through a complex network of genetic and epigenetic pathways. Dedifferentiation from somatic cells to iPSCs involves multiple genetic-epigenetic signaling pathways to obtain high levels of plasticity, self-renewal, motility and loss of specialized cellular functions. Eleven main signaling pathways have been involved in cell fate control and embryonic patterning. Extensive crosstalk among epigenetic pathways modifies DNA, histones and nucleosomes which make up the epigenetic mechanisms of gene regulation in differentiation and reprogramming processes.
The cellu lar differentiation process involves complex genetic, epigenetic and signaling pathways systems. The analysis of a specific model of cellular differentiation may contribute to understand the global mechanisms. The cellular differentiation process based on the experimental reprogramming of somatic cells (terminally differentiated cells) to induced pluripotent stem cells (iPSCs) can be used a study model of cellular differentiation. The cellular differentiation process includes constitutive changes in DNA damage response, chromatin remodeling, nuclear receptors, cell cycle regulation, apoptosis induction, cell adhesion and motility changes, immune recognition, metabolism routes, intercellular communication and in response to environment signals. It also includes the acquisition of changes into specialized cell subphenotypes as changes of shape, overproduction of organelles, suborganelles, control position of the mitotic spindle, preferential-transit signaling pathways and production of biomolecules with specialized functions. Different temporo-spatial genetic/epigenetic gene expression patterns and translational and posttranslational processes have been shown in the reprogramming of somatic cells. We analyze the main phenotype changes from fibroblast to iPSC (in cell cycle and cell adhesion/motility) to come after reprogramming, and use these changes as a model of cellular differentiation process.
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