RESUMEN
Innate immune cells such as natural killer (NK) cells play a crucial role in antitumor immune responses. NKG2D is a major activating immunoreceptor expressed in not only NK cells but also CD8+ T cells and shows cytotoxicity against tumors by recognizing its ligands major histocompatibility complex class I-related chain A and B (MICA and MICB) on tumor cells. Recently, it has been suggested that NKG2D-mediated cytotoxicity correlates with the expression levels of NKG2D ligands on target cells. In this study, we were able to increase the expression levels of MICA and MICB on leukemic cell lines and patients' leukemic cells by treatment with trichostatin A (TsA), a histone deacetylase (HDAC) inhibitor. Chromatin immunoprecipitation (ChIP) assays revealed that treatment with TsA resulted in increased acetylation of histone H3 and decreased association with HDAC1 at the promoters of MICA and MICB. Intriguingly, upregulation of MICA and MICB by treatment with TsA led to enhancement of the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. Our results suggest that regulation of the expression of NKG2D ligands by treatment with chromatin-remodeling drugs may be an attractive strategy for immunotherapy.
Asunto(s)
Regulación Leucémica de la Expresión Génica , Genes MHC Clase I , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase I/biosíntesis , Adulto , Anciano , Línea Celular Tumoral , Ensamble y Desensamble de Cromatina , Femenino , Antígenos de Histocompatibilidad Clase I/metabolismo , Histonas/metabolismo , Humanos , Ácidos Hidroxámicos/farmacología , Células Jurkat , Células K562 , Masculino , Persona de Mediana Edad , Subfamilia K de Receptores Similares a Lectina de Células NK , Inhibidores de la Síntesis de la Proteína/farmacología , Receptores Inmunológicos/metabolismo , Receptores de Células Asesinas NaturalesRESUMEN
Cubic, single-crystal, transparent Gd(3)Ga(5)O(12) has a density of 7.10 g/cm(3), a Hugoniot elastic limit of 30 GPa, and undergoes a continuous phase transition from 65 GPa to a quasi-incompressible (QI) phase at 120 GPa. Only diamond has a larger Hugoniot elastic limit. The QI phase of is more incompressible than diamond from 170 to 260 GPa. Electrical conductivity measurements indicate the QI phase has a band gap of 3.1 eV. Gd(3)Ga(5)O(12) can be used to obtain substantially higher pressures and lower temperatures in metallic fluid hydrogen than was achieved previously by shock reverberation between Al(2)O(3) disks.
RESUMEN
Transmission electron microscopic observation of forsterite (Mg(2)SiO(4)) shocked to peak pressures of 78 to 92 gigapascals revealed that forsterite breaks down to an assemblage of MgO plus MgSiO(3) glass. This strongly supports the interpretation that the high-pressure phase of forsterite under shock compression is due to the assemblage of MgSiO(3) perovskite plus MgO.
RESUMEN
Magnetic measurements have shown that nondiamagnetic minerals in a lunar crystalline rock of type B are (free Fe(2)+ in paramagnetic pyroxenes) : (antiferromagnetic FeSiO(3)) : (antiferromagnetic FeTiO(3)) : (ferromagnetic iron) = 4.3 : 7 : 20 : 0.08 in weight percentage. The abundance of ferromagnetic Fe in the lunar fines is about 7.5 times its abundance in the crystalline rock. The natural remanent magnetization of the crystalline rock of 7.5 x 10(-6) emu/ g in intensity may not be attributable to its thermoremanent magnetization.
