Anti-angiogenic theraphy for cancer and the mechanisms of tumor resistance

La progressió dels tumors requereix l'activació d'una neovascularització, o angiogènesi, un procés orquestrat per les cèl·lules tumorals i per l'estroma dins la massa tumoral. La inhibició terapèutica d'aquest procés té per objectiu impedir el creixement i la progressió del tumor. Actualment la terapèutica antiangiogènica s'aplica en determinats tipus de càncer. No obstant això, hi ha cèl·lules tumorals i components estromals que poden presentar una resistència variable a la terapèutica antiangiogènica, que pot ser refractarietat o resistència intrínseca, per una banda, o resistència adquirida progressivament al llarg del tractament, per una altra. S'han proposat diverses estratègies per lluitar contra aquests dos tipus de resistència, però encara han de provar-se en estudis preclínics i en assajos clínics.Tumor progression requires the activation of neovascularization, or angiogenesis, a process orchestrated by tumor and by stromal cells within the tumor mass. In the therapeutic targeting of angiogenesis, the aim is to inhibit tumor growth and progression. Indeed, anti-angiogenic therapy is currently used in several types of cancer. Nevertheless, both the tumor cells and the stromal components may be variably resistant to anti-angiogenic therapy, demonstrating refractoriness, or intrinsic resistance, on the one hand, and acquired resistance, gained progressively during treatment, on the other. Several strategies have been proposed to overcome both types of resistance but they remain to be tested in preclinical studies and clinical trials

Angiogenesis and Metabolism: Entwined for Therapy Resistance

Angiogenesis and metabolism are entwined processes that permit tumor growth and progression. Blood vessel supply is necessary for tumor survival by providing oxygen and nutrients for anabolism, but also by removing waste products from cellular metabolism. On the other hand, blocking angiogenesis with antiangiogenic therapies shows clinical benefits in several tumor types. Nevertheless, resistance to therapy emerges over time. In this review, we will discuss a novel mechanism of adaptive resistance involving metabolic adaptation of tumor cells, as well as provide examples of tumor adaptation to therapy, which may represent a new mechanism of resistance in several types of cancer. Thus, targeting this metabolic tumor adaptation could be a way to avoid resistance in cancer patients

Antiangiogenic Resistance: Novel Angiogenesis Axes Uncovered by Antiangiogenic Therapies Research

The mechanisms of tumor growth and progression involve the activation of different processes such as neovascularization and angiogenesis. These processes involve tumoral cells and stromal cells. Hence, inhibiting angiogenesis affects tumor growth and proliferation in patients with different types of cancer. Nevertheless, tumoral cells and stromal components are responsible for the resistance to antiangiogenic therapies. The majority of tumors respond to this type of therapy; however, some tumors may be indifferent to antiangiogenic therapies (intrinsic resistance) and other tumors become resistant during treatment (acquired resistance). Different strategies have been proposed to prevent resistance. Preclinical studies and clinical trials are focused to fight this therapeutic approach in order to prevent or delay tumor resistance to antiangiogenic therapies

Transaction management across data stores

Companies have evolved from a world where they only had SQL databases to a world where they use different kinds of data stores, such as key­value data stores, document­oriented data stores and graph databases. The reason why they have started to introduce this diversity of persistency models is because different NoSQL technologies bring different data models with associated query languages and/or APIs. However, they are confronted now with a problem in which they have the data scattered across different data stores. This problem lies in that when a business action requires to update the data, the data reside in different data stores, and they are subject to inconsistencies in the event of failure and/or concurrent access. These inconsistencies appear due to the lack of transactional consistency that was guaranteed in traditional SQL databases but is not guaranteed either within the NoSQL data stores or across data stores and databases. CoherentPaaS comes to remedy this need. CoherentPaaS provides an ultra­scalable transactional management layer that can be integrated with any data store with multi­ versioning capabilities. The layer has been integrated with six different data stores, three NoSQL data stores and three SQL­like databases. In this paper, we describe this generic ultra­scalable transactional management layer and focus on its API and how it can be integrated in different ways with different data stores and databases

A scalable SIEM correlation engine and its application to the Olympic Games IT infrastructure

The security event correlation scalability has become a major concern for security analysts and IT administrators when considering complex IT infrastructures that need to handle gargantuan amounts of events or wide correlation window spans. The current correlation capabilities of Security Information and Event Management (SIEM), based on a single node in centralized servers, have proved to be insufficient to process large event streams. This paper introduces a step forward in the current state of the art to address the aforementioned problems. The proposed model takes into account the two main aspects of this ?eld: distributed correlation and query parallelization. We present a case study of a multiple-step attack on the Olympic Games IT infrastructure to illustrate the applicability of our approach

Elaboración de una metodología para el cálculo del margen de intermediación financiera para la Asociación Solidarista de Trabajadores del Banco Popular y de Desarrollo Comunal y Afines

La presente investigación aborda las diferentes metodologías para el cálculo del margen de intermediación financiera que se han implementado en el sistema bancario costarricense, a la vez que busca proponer una metodología novedosa aplicada a una asociación solidarista, la cual presenta diferencias estructurales con respecto a estas instituciones. Por lo tanto, se consideran aspectos propios del solidarismo como movimiento obreropatronal, así como particularidades presentes en la estructura financiera de la Asociación Solidarista de Trabajadores del Banco Popular y de Desarrollo Comunal y Afines (Asebanpo), sobre todo en lo que respecta a sus fuentes de financiamiento. Lo anterior es con miras a presentar distintos panoramas según los cuales Asebanpo pueda optimizar su margen de intermediación, dando una base sobre la cual esta organización pueda construir una estrategia de negocio que redunde en mayores beneficios para sus asociados y en un empleo más eficiente de sus recursos a través de una gestión adecuada de sus activos, pasivos y patrimonio disponibles.UCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Ciencias Sociales::Maestría Profesional en Administración y Dirección de Empresas con énfasis en Finanza

Pre-clinical longitudinal monitoring of hemodynamic response to anti-vascular chemotherapy by hybrid diffuse optics

The longitudinal effect of an anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibody (DC 101) therapy on a xenografted renal cell carcinoma (RCC) mouse model was monitored using hybrid diffuse optics. Two groups of immunosuppressed male nude mice (seven treated, seven controls) were measured. Tumor microvascular blood flow, total hemoglobin concentration and blood oxygenation were investigated as potential biomarkers for the monitoring of the effect of therapy twice a week and were related to the final treatment outcome. These hemodynamic biomarkers have shown a clear differentiation between two groups by day four. Moreover, we have observed that pre-treatment values and early changes in hemodynamics are highly correlated with the therapeutic outcome demonstrating the potential of diffuse optics to predict the therapy response at an early time point. (C) 2017 Optical Society of Americ