Epigenetic Drugs Can Stimulate Metastasis through Enhanced Expression of the Pro-Metastatic Ezrin Gene

Ezrin has been reported to be upregulated in many tumors and to participate in metastatic progression. No study has addressed epigenetic modification in the regulation of Ezrin gene expression, the importance of which is unknown. Here, we report that highly metastatic rhabdomyosarcoma (RMS) cells with high levels of Ezrin have elevated acetyl-H3-K9 and tri-methyl-H3-K4 as well as reduced DNA methylation at the Ezrin gene promoter. Conversely, poorly metastatic RMS cells with low levels of Ezrin have reduced acetyl-H3-K9 and elevated methylation. Thus epigenetic covalent modifications to histones within nucleosomes of the Ezrin gene promoter are linked to Ezrin expression, which in fact can be regulated by epigenetic mechanisms. Notably, treatment with histone deacetylase (HDAC) inhibitors or DNA demethylating agents could restore Ezrin expression and stimulate the metastatic potential of poorly metastatic RMS cells characterized by low Ezrin levels. However, the ability of epigenetic drugs to stimulate metastasis in RMS cells was inhibited by expression of an Ezrin-specific shRNA. Our data demonstrate the potential risk associated with clinical application of broadly acting covalent epigenetic modifiers, and highlight the value of combination therapies that include agents specifically targeting potent pro-metastatic genes

Experimental Correlation of Combined Heat and Mass Transfer for NH 3 -H 2 0 falling film absorption

vection. The main conclusion from this study is that the negative concentration gradient of the surface tension is a trigger for inducement of Marangoni convection before the additive solubility, while the imbalance of the surface tension and the interfacial tension is a trigger after the solubility limit. Acknowledgment The authors thank Mr. K. Iizuka, Tokyo University of Agriculture and Technology, for his experimental assistance. The authors acknowledge that this work has been partially funded by the Japan Science and Technology Corporation (JST). References Beutler, A., Greiter, I., Wagner, A., Hohhmann, L., Schreier, S., and Alefeld, G., 1996, "Surfactants and Fluid Properties," Int. J. Refrigeration, Vol. 19, No. 5, pp. 342-346. Chavepeyer, G" Salajan, M., Platten, J. K., and Smet, P., 1995, "InterfacialTension and Surface Adsorption in j-Heptanol/Water Systems," Journal of Colloid and Interface Science, Vol. 174, Daiguji, H,, Hihara, E., and Saito, T., 1997, "Mechanism of Absorption Enhancement by Surfactant," Int. J. Heat and Mass Transfer, Vol. 40, No. 8, pp. 1743-1752. Fujita, T., 1993, "Falling Liquid Films in Absorption Machines," Int. J. Refrigeration, Vol. 16, No. 4, pp. 282-294. Hihara, E" and Saito, T., 1993 Journal of Heat Transfer TL = temperature of the fluid far away from the plate t' = time t R = reference time u = velocity of the fluid UD = reference velocity at' = frequency X,, = distance of the transition point from the leading edge |3 = coefficient of volume expansion p = density e = amplitude (constant) 9 = nondimensional temperature u = nondimensional velocity i = y-i Introduction Transient laminar-free convection flow past an infinite vertical plate under different plate conditions was studied by many researchers. The first closed-form solutions for Prandtl number Pr = 1.0 in case of a step change in wall temperature with time was derived by Illingworth (1950) and for Pr # 1.0, he derived the solution in integral form. Siegel (1958) studied the unsteady freeconvection flow past a semi-infinite vertical plate under stepchange in wall temperature or surface heat flux by employing the momentum integral method. Experimental evidence for such a situation was presented by Goldstein and Eckert (1960). For a semi-infinite vertical plate, unsteady free-convection flow was studied analytically b

ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population

EJA was funded by Barts and the London Charity (award 458/1495). MN was funded by a Medical Research Council Centenary Award

Vapor pressure data for fatty acids obtained using an adaptation of the DSC technique

The vapor pressure data for lauric (C-12:0), myristic (C-14:0), palmitic (C-16:0), stearic (C-18:0) and oleic (C-18:1) acids were obtained using Differential Scanning Calorimetry (DSC). the adjustments made in the experimental procedure included the use of a small sphere (tungsten carbide) placed over the pinhole of the crucible (diameter of 0.8 mm), making it possible to use a faster heating rate than that of the standard method and reducing the experimental time. the measurements were made in the pressure range from 1333 to 9333 Pa, using small sample quantities of fatty acids (3-5 mg) at a heating rate of 25K min(-1). the results showed the effectiveness of the technique under study, as evidenced by the low temperature deviations in relation to the data reported in the literature. the Antoine constants were fitted to the experimental data whose values are shown in Table 5. (C) 2012 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAEPEX/UNICAMPUniv Estadual Campinas, LPT, DPQ, Fac Engn Quim, BR-13083852 Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Ciencias Exatas & Terra, BR-09972270 Diadema, SP, BrazilUniv Estadual Campinas, EXTRAE, DEA, Fac Engn Alimentos, BR-13083862 Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Ciencias Exatas & Terra, BR-09972270 Diadema, SP, BrazilFAPESP: 2008/08706-1FAPESP: 2008/56258-8FAPESP: 2009/54137-1CNPq: 304495/2010-7CNPq: 480992/2009-6Web of Scienc

Application of seasonal borehole thermal energy storages into solar hybrid heating and cooling networks serving residential buildings in the Campania region of Italy: impact of meteorological data and underground characteristics

In this paper, 5 different case studies of solar hybrid heating and cooling networks satisfying thermal, cooling, electric and domestic hot water demands of 5 different small residential districts located into the 5 different provinces of the Campania region (southern Italy) have been modelled, dynamically simulated and analysed by means of the software TRNSYS over a 5-year period. Specific meteorological data files have been developed for each city based on 1-year in-situ hourly measurements in order to accurately take into account the influence of meteorological conditions on system performance; the effects of thermo-physical properties of underground have also been taken into consideration depending on location and according to measured data available in the scientific literature. The proposed plants have been compared with conventional Italian heating and cooling systems assumed as reference from energy, environmental and economic points of view in order to assess the potential savings, highlight the effects of both meteorological data and properties of underground as well as promote the diffusion of solar applications