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Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors
Carolina Méndez-Blanco,Flavia Fondevila,Andrés García-Palom,Javier González-Gallego,José L. Mauriz 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Sorafenib, a multikinase inhibitor with antiproliferative, antiangiogenic, and proapoptotic properties, constitutes the only effective first-line drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Despite its capacity to increase survival in HCC patients, its success is quite low in the long term owing to the development of resistant cells through several mechanisms. Among these mechanisms, the antiangiogenic effects of sustained sorafenib treatment induce a reduction of microvessel density, promoting intratumoral hypoxia and hypoxia-inducible factors (HIFs)-mediated cellular responses that favor the selection of resistant cells adapted to the hypoxic microenvironment. Clinical data have demonstrated that overexpressed HIF-1α and HIF-2α in HCC patients are reliable markers of a poor prognosis. Thus, the combination of current sorafenib treatment with gene therapy or inhibitors against HIFs have been documented as promising approaches to overcome sorafenib resistance both in vitro and in vivo. Because the depletion of one HIF-α subunit elevates the expression of the other HIF-α isoform through a compensatory loop, targeting both HIF-1α and HIF-2α would be a more interesting strategy than therapies that discriminate among HIF-α isoforms. In conclusion, there is a marked correlation between the hypoxic microenvironment and so
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Robust GPI Control of a New Parallel Rehabilitation Robot of Lower Extremities
Héctor Azcaray,Andrés Blanco,Carlos García,Manuel Adam,Juan Reyes,Gerardo Guerrero,César Guzmán 제어·로봇·시스템학회 2018 International Journal of Control, Automation, and Vol.16 No.5
In this paper, we propose a new robot for lower limbs rehabilitation by using a parallel structure. The goal of this robot is not only to produce smooth and precise motions for ankle, knee, and hip, but also to support trajectory tracking. Its parallel configuration was based on the four-bar mechanism in order to have a more stable and robust structure. For the kinematic analysis, the length of one bar was considered variable. For the dynamic analysis, the Euler-Lagrange method was used to define the equations of motion. For the robot control, the robust generalized proportional integral (GPI) controller was proposed to guarantee safe rehabilitation movements. This parallel robot not only showed good results, but also showed various movement possibilities for lower limbs rehabilitation.
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