RESUMEN
Published online: December 22, 2015 (DOI: 10.4238/2015.December.22.11). Corrected after publication: June 3, 2016 (DOI: 10.4238/gmr.150267861). The correction is only in the name of the last author and should be: W.J. Wang, S.J. Yin and R.Q. Guo.
RESUMEN
Immune cells might participate in the ontogenesis of osteosarcoma. B7-H3 is a new discovered T cell co-stimulatory molecule that was found to be overexpressed in malignant tumors. We aimed to investigate the dynamic expression level of B7-H3 in nude mice with osteosarcoma. A nude mouse osteosarcoma model was successfully established. B7-H3 expression and distribution changes in the early, middle, and late phases of osteosarcoma formation after tumor implantation were observed. Reverse transcription-polymerase chain reaction and western blot analyses were applied to measure the B7-H3 mRNA and protein dynamic changes. Confocal microscopy and immunohistochemistry were used to determine B7-H3 localization and CD3+ T cell expression, respectively, in osteosarcoma tissue. B7-H3 mRNA and protein levels fluctuated during the process of osteosarcoma formation in the nude mouse model. Expression levels were lower in the early and middle phases, while B7-H3 mRNA and protein were overexpressed in the late stage. Accordingly, CD3+ T cell numbers in the early, middle, and late phases in osteosarcoma tissue were 93 ± 13, 92 ± 12, and 46 ± 15, respectively; they can be seen to have decreased significantly in the late stage (P < 0.05). Overall, our results indicated that the B7-H3 expression level is correlated with tumor volume and severity; therefore, it might serve as a tumor biomarker for osteosarcoma.
Asunto(s)
Antígenos B7/biosíntesis , Neoplasias Óseas/metabolismo , Osteosarcoma/metabolismo , Animales , Antígenos B7/genética , Antígenos B7/inmunología , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Neoplasias Óseas/genética , Neoplasias Óseas/inmunología , Neoplasias Óseas/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Ratones , Ratones Desnudos , Osteosarcoma/genética , Osteosarcoma/inmunología , Osteosarcoma/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T/inmunologíaRESUMEN
The pathogenesis of rheumatoid arthritis (RA) is characterized by inflammation. We aimed to examine the roles of double-stranded RNA-activated protein kinase (PKR) and high-mobility group box chromosomal protein 1 (HMGB1) in a rat model of RA. Male SD rats were divided into three groups: control, RA model, and intervention (RA model plus treatment). The model of RA was made by injecting Freund's adjuvant into the posterior right limb of the rat and the intervention group received a PKR-specific inhibitor C16 after RA modeling. The degree of limb swelling was measured following RA modeling and intervention. In addition, plasma levels of HMGB1 were determined using ELISA. The mRNA and protein levels of PKR and HMGB1 were detected in rat synovium using quantitative PCR and western blot, respectively. The degree of limb swelling in the RA model was increased compared to control, while it was decreased in the intervention model compared to the RA model. Plasma HMGB1 levels in the model group were significantly higher compared to the control group but were lower in the intervention group compared to the model group. PKR and HMGB1 protein and mRNA levels in the rat synovium were elevated in the model group and markedly reduced in the intervention group. Increased levels of PKR and HMGB1 in synovium or blood appear to be involved in the occurrence and development of RA in a rat model. Selective inhibition of PKR improves the symptoms of RA, perhaps by inhibiting the release of HMGB1.
Asunto(s)
Artritis Reumatoide/genética , Proteína HMGB1/biosíntesis , Inflamación/genética , Membrana Sinovial/metabolismo , eIF-2 Quinasa/biosíntesis , Animales , Artritis Reumatoide/patología , Modelos Animales de Enfermedad , Proteína HMGB1/genética , Humanos , Inflamación/patología , Masculino , ARN Bicatenario/genética , ARN Mensajero/biosíntesis , Ratas , Membrana Sinovial/patología , eIF-2 Quinasa/genéticaRESUMEN
Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specifically, controls have higher frequencies of the variants with higher Vmax (ADH2*2 and ADH3*1). In samples both of alcoholics and of controls from three Taiwanese populations (Chinese, Ami, and Atayal) we found significant pairwise disequilibrium for all comparisons of the two functional polymorphisms and a third, presumably neutral, intronic polymorphism in ADH2. The class I ADH genes all lie within 80 kb on chromosome 4; thus, variants are not inherited independently, and haplotypes must be analyzed when evaluating the risk of alcoholism. In the Taiwanese Chinese we found that, only among those chromosomes containing the ADH3*1 variant (high Vmax), the proportions of chromosomes with ADH2*1 (low Vmax) and those with ADH2*2 (high Vmax) are significantly different between alcoholics and controls (P<10-5). The proportions of chromosomes with ADH3*1 and those with ADH3*2 are not significantly different between alcoholics and controls, on a constant ADH2 background (with ADH2*1, P=.83; with ADH2*2, P=.53). Thus, the observed differences in the frequency of the functional polymorphism at ADH3, between alcoholics and controls, can be accounted for by the disequilibrium with ADH2 in this population.