RESUMEN
BACKGROUND/AIMS: Immunosuppression is one of the hallmarks of cancer; however, its molecular mechanism remains unknown. In the present study, we sought to investigate the expression and activation of yes-associated protein 1 (YAP-1) and its roles in T cells within hepatocellular carcinoma (HCC). METHODS: The expression and activation of YAP-1 were accessed by real-time PCR, immunohistochemistry staining, western blot, and flow cytometry. The potential regulation effect of YAP-1 on Regulatory T cells (Tregs) differentiation was predicted using bioinformatics tools and verified by in vitro studies. RESULTS: Significant overexpression and activation of YAP-1 was detected within peripheral blood mononuclear cells and showed positive linear correlation to Treg percentage; it may serve as a valuable indicator of a bad prognosis. Using in vitro studies, we found that overexpression and activation of YAP-1 can promote naïve T cell polarization stimulation to Tregs by increasing the expression of TGFBR2. The YAP-1/TEADs DNA binding site was spotted within the promoter region of TGFBR2 and related to its transcription activity. YAP-1 acted as a co-activator of TGFBR2 transcription by binding directly to the TGFBR2 promoter through TEADs. CONCLUSION: Overexpression and activation of YAP-1 in HCC T cells can induce immunosuppression by promoting Treg differentiation via transcriptional enhancement of TGFBR2.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinasas/genética , Receptores de Factores de Crecimiento Transformadores beta/genética , Linfocitos T Reguladores/inmunología , Proteínas Adaptadoras Transductoras de Señales/inmunología , Adulto , Sitios de Unión , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Diferenciación Celular , Proliferación Celular , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Proteínas Nucleares/inmunología , Fosfoproteínas/inmunología , Cultivo Primario de Células , Regiones Promotoras Genéticas , Unión Proteica , Proteínas Serina-Treonina Quinasas/inmunología , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/inmunología , Transducción de Señal , Linfocitos T Reguladores/patología , Factores de Transcripción de Dominio TEA , Factores de Transcripción/genética , Factores de Transcripción/inmunología , Transcripción Genética , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND: This study aimed to investigate the mechanism of galectin (Gal)-1 of regulating Treg/Th17 in pathogenesis of acute rejection after liver transplantation in rat. METHODS: Mononuclear cells were induced to immature dendritic cells (imDCs), which were transfected with or without NF-κB/RelB. Western Blot was performed to detect the expression of NF-κB/RelB. the expression of CD11c, CD45RB, CD80 and MHC II were detected by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokines IL-27 and TGF-ß. Lewis and dark agouti (DA) rats were generally anaesthetized by isoflurane inhalation to establish liver transplant models. RESULTS: We demonstrate that Gal-1 disturbs maturation of imDCs by downregulating NF-κB/RelB expression, and Gal-1 negatively controls CD4+ proliferation though IL-27 pathway. CONCLUSIONS: In aggregate, Gal-1 promotes Treg differentiation in CD4+ T cells though NF-κB/RelB-IL-27 pathway. These findings suggest a new therapeutic target to mediate Treg population.
RESUMEN
OBJECTIVE: We evaluated microwave-assisted liver resection for hepatocellular carcinoma. PATIENTS AND METHODS: We enrolled 79 patients in this study, and microwave ablation was used for liver resection. Patients were randomized to group A (50.6%; n = 40), liver resection without microwave ablation, or group B (49.4%; n = 39), liver resection performed using microwave ablation. Data were analyzed for statistical significance. RESULTS: Of the participants enrolled, 60 were male, and the participant's average age was 59.32 ± 10.34 years. The mean overall tumor diameter was 4.39 (2.00) cm, and this did not differ between groups. Intraoperative blood loss in group B was significantly less than that in group A ( P < .001). No differences were reported between the 2 groups regarding surgical time ( P = .914), postoperative morbidity ( P = .718), and late postoperative complications ( P = .409). Postoperative drainage volume for group B was less than that of group A on the first ( P = .005) and third ( P = .019) day after surgery. The time of postoperative hospitalization in group B was significantly shorter than that in group A ( P < .001). Local recurrence was noted in 18.99% of cases (n = 15) in group B, which is less than that of group A ( P = 0.047), while in group B distant metastasis is less but not statistically significant ( P = 0.061). The 1-year and 3-year cumulative survival rates were 57% and 93.7%, respectively. CONCLUSIONS: The curative effects of liver resection combined with microwave ablation during operation are superior to only liver resection in the treatment of primary liver cancer.