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Juan Pablo Rigalli Nadia Ciriaci Agostina Arias María Paula Ceballos Silvina Stella Maris Villanueva Marcelo Gabriel Luquita Aldo Domingo Mottino Carolina Inés Ghanem Viviana Alicia Catania María Laura Ruiz 《PloS one》2015,10(3)
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide. Sorafenib is the only drug available that improves the overall survival of HCC patients. P-glycoprotein (P-gp), Multidrug resistance-associated proteins 2 and 3 (MRP2 and 3) and Breast cancer resistance protein (BCRP) are efflux pumps that play a key role in cancer chemoresistance. Their modulation by dietary compounds may affect the intracellular accumulation and therapeutic efficacy of drugs that are substrates of these transporters. Genistein (GNT) is a phytoestrogen abundant in soybean that exerts its genomic effects through Estrogen-Receptors and Pregnane-X-Receptor (PXR), which are involved in the regulation of the above-mentioned transporters. We evaluated the effect of GNT on the expression and activity of P-gp, MRP2, MRP3 and BCRP in HCC-derived HepG2 cells. GNT (at 1.0 and 10 μM) increased P-gp and MRP2 protein expression and activity, correlating well with an increased resistance to sorafenib cytotoxicity as detected by the methylthiazole tetrazolium (MTT) assay. GNT induced P-gp and MRP2 mRNA expression at 10 but not at 1.0 μM concentration suggesting a different pattern of regulation depending on the concentration. Induction of both transporters by 1.0 μM GNT was prevented by cycloheximide, suggesting translational regulation. Downregulation of expression of the miR-379 by GNT could be associated with translational regulation of MRP2. Silencing of PXR abolished P-gp induction by GNT (at 1.0 and 10 μM) and MRP2 induction by GNT (only at 10 μM), suggesting partial mediation of GNT effects by PXR. Taken together, the data suggest the possibility of nutrient-drug interactions leading to enhanced chemoresistance in HCC when GNT is ingested with soy rich diets or dietary supplements. 相似文献
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Genomic Resources Development Consortium Mariella Baratti Federica Cattonaro Tiziana Di Lorenzo Diana Maria Paola Galassi Valentina Iannilli Alessio Iannucci Just Jensen Peter Foged Larsen Rasmus O. Nielsen Cino Pertoldi Dragos Postolache Jose Martin Pujolar Ettore Randi Aritz Ruiz‐Gonzalez Janne Pia Thirstrup Giovanni Giuseppe Vendramin Andrzej Zalewski 《Molecular ecology resources》2015,15(2):458-459
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Sara Garcia‐Serrano Carolina Gutiérrez‐Repiso Montserrat Gonzalo Juan Garcia‐Arnes Sergio Valdes Federico Soriguer Vidal Perez‐Valero Miguel A. Alaminos‐Castillo Juan Francisco Cobos‐Bravo Francisco J. Moreno‐Ruiz Alberto Rodriguez‐Cañete Francisca Rodríguez‐Pacheco Eva Garcia‐Escobar Eduardo García‐Fuentes 《Obesity (Silver Spring, Md.)》2015,23(8):1607-1615
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Donna L Rogers Gloria B McClure Julio C Ruiz Christian R Abee John A Vanchiere 《Comparative medicine》2015,65(3):232-240
Nonhuman primates are the experimental animals of choice for the study of many human diseases. As such, it is important to understand that endemic viruses of primates can potentially affect the design, methods, and results of biomedical studies designed to model human disease. Here we review the viruses known to be endemic in squirrel monkeys (Saimiri spp.). The pathogenic potential of these viruses in squirrel monkeys that undergo experimental manipulation remains largely unexplored but may have implications regarding the use of squirrel monkeys in biomedical research.Abbreviations: HTLV1, human T-cell leukemia virus type 1; HVS, herpesvirus saimiri; IPF, idiopathic pulmonary fibrosis; SaHV, Saimiriine herpesvirus; SFV, simian foamy virus; SM-CMV, squirrel monkey cytomegalovirus; SMPyV, squirrel monkey polyomavirus; SMRV, squirrel monkey retrovirusThe similarity between the nonhuman primate and human immune systems is a key advantage in the use of nonhuman primates compared with other mammalian models of human disease.13,71,88,94,103,113,125 In addition, the diversity of environmental and infectious disease agents encountered by primates is similar to that of humans, providing nonhuman primates a comparable level of biologic complexity.1 Old World primates, such as macaques and baboons, and New World primates, including squirrel monkeys and marmosets, are commonly used in biomedical research. Squirrel monkeys (Saimiri spp.) are neotropical primates native to the forests of Central and South America. Of the 7 species of squirrel monkey, 3 (S. oerstedii, S. vanzolinii, and S. ustus) are classified as endangered, vulnerable to extinction in the wild, or near threatened, whereas the remaining 4 (S. boliviensis, S. cassiquiarensis, S. macrodon, and S. sciureus) are not endangered, although the S. cassiquiarensis albigena subspecies is near threatened52,81 (Figure 1). In South America, where squirrel monkeys are indigenous, breeding colonies of S. sciureus have been maintained at the Pasteur Institute in French Guiana and at the Oswaldo Cruz Foundation in Brazil.7,12 In the United States, the Squirrel Monkey Breeding and Research Resource, an NIH-sponsored national research resource, maintains breeding colonies for S. boliviensis boliviensis, S. sciureus sciureus, and S. boliviensis peruviensis.Open in a separate windowFigure 1.Taxonomy of Saimiri species with associated IUCN designations.52,81Squirrel monkeys adapt easily to laboratory housing and can be housed in smaller spaces than can Old World primates.1 Unlike when working with Old World primates, particularly macaques, no additional personnel protective equipment is necessary when working with squirrel monkeys beyond that recommended for working with other New World primates.92 Their small size, combined with the reduced need for personnel protective equipment during handling, make squirrel monkeys attractive species for model development and for studies of viral pathogenesis, which cost approximately 30% to 40% less than comparable studies in macaques.1 The likelihood of zoonotic transmission of infectious pathogens is considerably less than that associated with macaques and the risk of Macacine herpesvirus 1 (B virus) is nonexistent, given that neotropical primates do not harbor this lethal virus.1 These factors are increasingly important in the current climate of limited grant funding for biomedical research and emphasis on safety for laboratory personnel. The limited availability of immunologic reagents with specificity for neotropical primates has hindered broader use of squirrel monkeys in biomedical research, compared with that of the more commonly used Old World primates. In addition, the small size of neotropical primates limits the volume of blood that can be collected at any one time. To abrogate these limitations, the NIH Nonhuman Primate Reagent Resource (www.nhpreagents.org) provides an increasing repertoire of agents that have been characterized for immunologic studies of neotropical primates.89Squirrel monkeys are used in numerous aspects of biomedical research, including studies of viral persistence, neuroendocrinology, infectious diseases, cancer treatments, vaccine development, gene expression, and reproductive physiology.117 The similarity between the squirrel monkey immune system and that of humans means that, as with macaques, there is a high likelihood that research outcomes will recapitulate what occurs in human diseases.13,71,87,94 This is particularly true for the study of several notable infectious diseases, including malaria, Creutzfeldt–Jakob disease, and human T-cell leukemia virus type 1 (HTLV1) infection.19,56,128 For these diseases, squirrel monkeys are the model system of choice for studying pathogenesis, experimental treatments, and strategies for prevention.Squirrel monkeys are recognized as some of the most susceptible nonhuman primate species for the experimental transmission of Creutzfeldt–Jakob disease and other transmissible spongiform encephalopathies that cause chronic wasting disease.11,72,98,130 The experimental infection of squirrel monkeys with HTLV1 has led to their use in vaccine development and chemotherapy research directed against HTLV1.44,57,58,82 In addition, squirrel monkeys are an important model for studying the immunology of malaria and for testing vaccines against several Plasmodium species.19,20,68,114 Furthermore, squirrel monkeys have been used in pharmacologic research to raise HDL levels to prevent atherosclerosis and reduce the risk of coronary heart disease.6 As the use of squirrel monkeys increases, especially for infectious disease research, accurate information about the endemic viral infections of squirrel monkeys is needed because of the potential for zoonotic transfer of these viruses to humans (and vice versa) and to understand the potential influence these agents may have on research involving other infectious pathogens diseases and immunosuppressive drugs. 相似文献
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Juan Ignacio Ruiz Kaamel Nuhu Justin Tyler McDaniel Federico Popoff Ariel Izcovich Juan Martin Criniti 《PloS one》2015,10(10)