Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18

Background: Implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanisms. A hepatic melanoma metastasis model where a majority of metastases are generated via interleukin-18-dependent mechanisms was used to test whether anti-inflammatory properties of resveratrol can interfere with mechanisms of metastasis. Methods: Two experimental treatment schedules were used: 1) Mice received one daily oral dose of 1 mg/kg resveratrol after cancer cell injection and the metastasis number and volume were determined on day 12. 2) Mice received one daily oral dose of 1 mg/kg resveratrol along the 5 days prior to the injection of cancer cells and both interleukin-18 (IL-18) concentration in the hepatic blood and microvascular retention of luciferase-transfected B16M cells were determined on the 18(th) hour. In vitro, primary cultured hepatic sinusoidal endothelial cells were treated with B16M-conditioned medium to mimic their in vivo activation by tumor-derived factors and the effect of resveratrol on IL-18 secretion, on vascular cell adhesion molecule-1 (VCAM-1) expression and on tumor cell adhesion were studied. The effect of resveratrol on melanoma cell activation by IL-18 was also studied. Results: Resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion-and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells. Conclusions: These results demonstrate multiple sites for therapeutic intervention using resveratrol within the prometastatic microenvironment generated by tumor-induced hepatic IL-18, and suggest a remarkable effect of resveratrol in the prevention of inflammation-dependent melanoma metastasis in the liver.

Experimental Economics Meets Language Choice

Roughly one half of World's languages are in danger of extinction. The endangered languages, spoken by minorities, typically compete with powerful languages such as En- glish or Spanish. Consequently, the speakers of minority languages have to consider that not everybody can speak their language, converting the language choice into strategic,coordination-like situation. We show experimentally that the displacement of minority languages may be partially explained by the imperfect information about the linguistic type of the partner, leading to frequent failure to coordinate on the minority language even between two speakers who can and prefer to use it. The extent of miscoordination correlates with how minoritarian a language is and with the real-life linguistic condition of subjects: the more endangered a language the harder it is to coordinate on its use, and people on whom the language survival relies the most acquire behavioral strategies that lower its use. Our game-theoretical treatment of the issue provides a new perspective for linguistic policies.

Implementación de un sistema de adquisición de datos analógico para la medida experimental de la posición y aceleración.

[ES]El objetivo de este proyecto es el desarrollo de un sistema de adquisición y tratamiento de señales analógicas para la medida experimental de la posición y aceleración. Por un lado, la adquisición de señales se llevará a cabo mediante una placa electrónica programable llamada “Arduino”. Por otro lado, haciendo uso de la plataforma LabVIEW, se creará un programa para analizar dichas señales. Se medirán señales analógicas provenientes de diferentes sensores (inclinómetros y acelerómetros).