Endometrial carcinomas, the most common malignant tumour of the female genital tract, are usually diagnosed at an early stage with uterine-confined disease and an overall favourable prognosis. However, up to 20% of endometrial carcinomas will end up in recurrent disease, associated with a drop in survival and representing the major clinical challenge. Management of this group of risk patients relies on robust biomarkers that may predict which endometrial carcinomas will relapse. For this, we performed a proteomic analysis comparing primary lesions with recurrences and identified ANXA2 as a potential biomarker associated with recurrent disease that we further validated in an independent series of samples by immunohistochemistry. We demonstrated in vitro a role for ANXA2 in the promotion of metastasis rather than interfering with sensitivity to radio/chemotherapy. In addition, ANXA2 silencing resulted in a reduced metastatic pattern in a mice model of endometrial cancer dissemination, with a limited presence of circulating tumor cells. Finally, a retrospective study in a cohort of 93 patients showed that ANXA2 effectively predicted those endometrioid endometrial carcinomas that finally recurred. Importantly, ANXA2 demonstrated a predictive value also among low risk Stage I endometrioid endometrial carcinomas, highlighting the clinical utility of ANXA2 biomarker as predictor of recurrent disease in endometrial cancer. Retrospective and prospective studies are ongoing to validate ANXA2 as a potential tool for optimal stratification of patients susceptible to receive radical surgery and radio/chemotherapy.Endometrial carcinoma is the most common tumor of the female genital tract, with an increasing incidence. Although usually diagnosed at an early stage with uterine-confined disease and an overall favorable prognosis, up to 20% of endometrial carcinomas are at substantial risk of recurrence and death. In addition and although spread to regional lymph
Few types of cancer have had their treatment evolve as rapidly as metastatic renal cell carcinoma (mRCC). Since 2005, six new targeted therapies with proven efficacy have been approved for the treatment of mRCC. The downside is that our knowledge about the mechanisms of action of these therapies and the intrinsic and extrinsic mechanism of resistance has not evolved equally fast, and many questions remain unanswered. The only approved agent to date in the European Union for patients who progress on sunitinib or sorafenib is everolimus. The results of the phase III trial comparing axitinib vs. sorafenib after failure on sunitinib, bevacizumab, temsirolimus, or cytokines have recently been published, and axitinib has recently been licensed by the Food and Drugs Administration. Other phase III trials that are being conducted include a comparison between everolimus plus bevacizumab and everolimus after failure on tyrosine kinase inhibitors, and between temsirolimus and sorafenib after failure on sunitinib. In this article, we will review the available evidence from clinical studies on sequential therapy for mRCC, including those that are still in progress. In addition, information on the mechanism of resistance or tolerance to first-line therapy, recommendations of the main practice guidelines for second-line treatment, potential therapies for third or successive treatment lines, and the major reasons why patients who progress may benefit from a change of mechanism of action will also be discussed.
Based on World Health Organization criteria, anemia was found in 25.4% of elderly subjects studied. Iron deficiency seems to be the main cause of anemia, and chronic disease the second cause of anemia. Dietary intake is not one of the principal causes of anemia in the study population, except for folate intake.
Palabras clave: Evaluación, política regional, evaluación basada en la teoría.
IntroducciónEn las dos últimas décadas se han producido cambios de gran importancia en las estrategias de actuación regional y en sus políticas. ¿Es posible hablar de una nueva generación de políticas regionales? Para muchos investigadores, el nuevo paradigma regional que comienza a configurarse a lo largo de los años 90 ofrece un marco teórico suficientemente consolidado como para convertirse en la base conceptual e interpretativa sobre la que construir una nueva política regional, un nuevo diseño basado en la definición de estrategias dirigidas hacia la movilización de los recursos locales, pero donde las ventajas competitivas de las regiones se construyen sobre nuevos parámetros como el aprendizaje localizado, la construcción de redes de asociación y la base institucional de la región (Amin 1998;Cooke y Morgan 1998;Cooke et al. 2000;Landabaso 2000; Morgan y Nauwelaers 1999;Storper 1997).Esta nueva política regional implica un cambio radical y supone un punto de inflexión con las políticas anteriores. Como algunos autores señalan, «la política regional tradicional se ha venido ocupando de la construcción de infraestructuras físicas, mientras que el nuevo acento se sitúa sobre la construcción del capital social -esto es, sobre una infraestructura relacional para la acción colectiva basada en la confianza, la reciprocidad y la disposición a colaborar con fines beneficiosos mutuos, los llamados factores intangibles que, hoy en día, están considerados como elementos fundamentales para el desarrollo económico y la innovación» (Morgan y Nauwelaers 1999: 4). Estos factores intangibles no deben ser entendidos como un activo regional que sólo se desarrolla de manera espontánea en espacios geográficos e históricos específicos, sino como un capital que puede ser positivamente potenciado a través de la intervención pública. El objetivo final de estas nuevas políticas es mejorar la capacidad de absorción del conocimiento mediante actuaciones dirigidas a incrementar el potencial de aprendizaje de toda la sociedad regional en su conjunto, incluidas sus instituciones (Asheim 1999: 6).
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