Cáncer, genes y genomas

Cancer is a disease whose ability to make us feel vulnerable seems to increase every day. The World Health Organization’s forecasts for the year 2020 speak of 16 million new diagnoses and 10 million fatal victims. However, despite these overwhelming numbers that almost liken cancer to a modern epidemic, we are not facing a recent pathology, just remember its origin to convince ourselves of this. Indeed, after the formation of the first cells more than three billion years ago, life on our planet took place in an exclusively unicellular environment. Millennium after millennium, unicellular life dominated the Earth until about 800 million years ago, one of these primitive cells successfully shared its life with others like it, initiating the process that led them to build multicellular organisms. It was also at that moment when the first pathways that would later lead to cancer began to take shapeEl cáncer es una enfermedad cuya capacidad para hacernos sentir vulnerables parece aumentar cada día. Las previsiones de la Organización Mundial de la Salud para el año 2020 hablan de 16 millones de nuevos diagnósticos y 10 millones de víctimas mortales. Sin embargo, pese a estos números abrumadores que casi asemejan el cáncer a una epidemia moderna, no estamos ante una patología reciente, basta recordar su origen para convencernos de ello. En efecto, tras la formación de las primeras células hace más de tres mil millones de años, la vida en nuestro planeta transcurrió en un ámbito exclusivamente unicelular. Milenio tras milenio, la vida unicelular dominó la Tierra hasta que hace unos 800 millones de años, una de es- tas células primigenias compartió con éxito su vida con otras semejantes, iniciando el proceso que las condujo a construir organismos multicelulares. Fue también en ese momento cuando comenzaron a gestarse las primeras vías que más tarde conducirían al cáncer. &nbsp

La investigación oncológica en España

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La investigación oncológica en España

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Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness

Conditions resulting from loss of cellular homeostasis, including oxidative stress, inflammation, protein aggregation, endoplasmic reticulum stress, metabolic stress, and perturbation of mitochondrial function, are common to many pathological disorders and contribute to aging. Cells face these stress situations by engaging quality control mechanisms aimed to restore cellular homeostasis and preserve cell viability. Among them, the autophagy-lysosomal pathway mediates the specific degradation of damaged proteins and organelles, and its proper function is related to cellular protection and increased life span in many model organisms. Besides autophagy, increasing evidence underscores a role for exosomes in the selective secretion of harmful/damaged proteins and RNAs and thus in the maintenance of cellular fitness. In this perspective article, we discuss the emerging function of exosomes as a means of alleviating intracellular stress conditions, and how secretion of harmful or unwanted material in exosomes, in coordination with the autophagy-lysosomal pathway, is essential to preserve intracellular protein and RNA homeostasis. Finally, we provide an overview about the consequences of the spreading of the exosome content in physiological and pathological situations, and suggest putative therapeutic strategies for these exosome-mediated alterations.S

Rejuvenating somatotropic signaling: a therapeutical opportunity for premature aging?

We have recently reported that progeroid Zmpste24−/− mice, which exhibit multiple defects that phenocopy Hutchinson-Gilford progeria syndrome, show a profound dysregulation of somatotropic axis, mainly characterized by the occurrence of very high circulating levels of growth hormone (GH) and a drastic reduction in insulin-like growth factor-1 (IGF-1). We have also shown that restoration of the proper GH/IGF-1 balance in Zmpste24−/− mice by treatment with recombinant IGF-1 delays the onset of many progeroid features in these animals and significantly extends their lifespan. Here, we summarize these observations and discuss the importance of GH/IGF-1 balance in longevity as well as its modulation as a putative therapeutic strategy for the treatment of human progeroid syndromes

Protease Addiction and Synthetic Lethality in Cancer

The “oncogene addiction” concept refers to the dependence of cancer cells on the function of the oncogenes responsible for their transformed phenotype, while the term “non-oncogene addiction” has been introduced to define the exacerbated necessity of the normal function of non-mutated genes. In this Perspective, we focus on the importance of proteolytic enzymes to maintain the viability of cancer cells and hypothesize that most, if not all, tumors present “addiction” to a number of proteolytic activities, which in turn may represent valuable targets of anti-cancer therapies, even without being mutated or over-expressed by the malignant cells

La evolución de la Educación Física en la etapa de Educación Primaria: Revisión teórica desde su implantación como asignatura a mediados del s. XIX hasta nuestros días.

Este trabajo, de revisión, pretende acercar al lector al cambio continuo que ha experimentado la Educación Física desde su puesta en marcha en los planes de estudio hacia mediados del s. XIX. El estudio describe, por tanto, las diversas metodologías propuestas para la enseñanza de la asignatura y su cambio constante en función de los intereses políticos. Al mismo tiempo que expone las diferencias entre ambos sexos transportadas durante su desarrollo, y como finalmente se solventan

Expression of collagenase-3 in the rat ovary during the ovulatory process.

We have examined the expression of the murine counterpart of human collagenase-3, a matrix metalloproteinase produced by breast carcinomas, in the course of processes which involve extensive tissue remodeling. By using Northern blot analysis, we have found that collagenase-3 is expressed in the rat ovary, but not in the remaining analyzed tissues including brain, kidney, liver, lung, mammary gland, uterus, bladder, heart, intestine, prostate, spleen, testis and thymus. Collagenase-3 mRNA was detected at high levels in rat ovaries at proestrus and estrus, was at a minimum at metestrus and started to increase during diestrus through to proestrus. In addition, collagenase-3 was also detected on day 21 of pregnancy, which is approximately one day before parturition. However, no significative expression was detected in RNA from ovaries taken immediately after parturition, or on days 1, 5 or 30 postpartum. Northern blot analysis also revealed that collagenase-3 was not expressed at significant levels, compared with ovarian expression, in the uterus or in the mammary gland during pregnancy or after parturition. When follicular granulosa cells were separated from Northern blot, it was seen that collagenase-3 was not expressed by the granulosa cells but was present in the residual tissue containing interstitial and thecal tissues, growing follicles and corpora lutea. Immunohistochemical studies also confirmed, at the protein level, the localization of collagenase-3 in rat ovary. Gonadotropic stimulation of ovulation in immature rats by priming with pregnant mare's serum gonadotropin and stimulation with human chorionic gonadotropin failed to induce the expression of collagenase-3, suggesting that additional factors which are not present in the immature stimulated rats are needed for completely effective induction of the expression of this matrix metalloproteinase. On the basis of these results, together with the comparative analysis of expression of different matrix metalloproteinases in the rat ovary, we propose that collagenase-3 is a major ovarian metalloproteinase potentially involved in ovarian function during the reproductive cycle.Comisión Interministerial de Ciencia y Tecnología (SAF94-0892

Glucocorticoids and androgens up-regulate the Zn-α 2-glycoprotein messenger RNA in human breast cancer cells

Se trata de una publicación que detalla los trabajos realizados para conocer los mecanismos que regulan la expresión de la Zn-α2-glicoproteina (Zn-α2-gp) en células de cáncer de mama y verificar si existe un antagonismo entre la proliferación celular y la producción de Zn-α2-gp. Esta glicoproteína es una de las proteínas mayoritarias identificadas en la enfermedad quística mamaria. Además, estudios realizados en nuestro laboratorio han puesto en evidencia su presencia en citosoles de carcinomas mamarios y su potencial utilidad como marcador tumoral. Se desconoce el papel biológico de esta proteína, pero dado que su secuencia de aminoácidos tiene una extensa similitud estructural con los antígenos del complejo mayor de histocompatibilidad (HLA) humano se especula su posible función en la respuesta inmune como un HLA soluble. Los resultados muestran que tanto la dexametasona como La 5 α-dihidrotestosterona indujeron fuertemente la acumulación de ARNm de Zn-α2-gp en células de cáncer de mama humano T-47D. Además, observamos que el efecto de estas dos hormonas fue aditivo, ya que su combinación produjo una estimulación del ARNm de Zn-α2-gp 3 veces mayor que la producida por cualquiera de las dos hormonas por separado. Por el contrario, la adición de 5-beta-dihidrotestosterona, 17-beta-estradiol o progesterona no logró inducir la expresión de Zn-α2-gp. El efecto estimulador de los glucocorticoides y andrógenos sobre la expresión de Zn-a2-gp se produjo de manera dependiente del tiempo y la dosis, sin afectar significativamente la tasa de proliferación celular. Estos resultados nos han permitido proponer que la Zn-α2-gp puede ser útil como marcador bioquímico de carcinomas de mama con un patrón específico de capacidad de respuesta hormonal en cuyo desarrollo los glucocorticoides y/o los andrógenos pueden desempeñar un papel importante.Comisión Interministerial de Ciencia y Tecnología, Plan Nacional de I + D