ABSTRACT
The HLA-I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The loss of surface expression of HLA-I molecules is particularly important as this enables tumor cells to evade recognition and lysis by cytotoxic T-lymphocytes. Transcriptional control of the APM genes is regulated by the nuclear factor kappa B (NF-κB). BCRFl is an Epstein-Barr virus homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). vIL-10 shares many immunosuppressive effects with hIL-10 but lacks the immunostimulatory effect of hIL-10. The aim of this study was to assess whether vIL-10 inhibits APM components (TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I) through the NF-κB signaling pathway in nasopharyngeal carcinoma. This work demonstrated that vIL-10 inhibited NF-κB activation by blocking IKK phosphorylation and promoting the expression of IKB. TNF-α treatment led to a strong translocation of NF-κB p65, whereas pretreatment with vIL-10 before TNF-α treatment blocked NF-κB p65 translocation. vIL-10 also inhibited TNF-α-induced DNA-binding of NF-κB p65 in the nucleus. Furthermore, chromatin immunoprecipitation analysis demonstrated that NF-κB p65 could bind to the TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I gene promoters, and after TNF-α stimulation, the down-regulation of TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I transcription by vIL-10 correlated with the suppression of NF-κB in CNE-2 cells. Surprisingly, vIL-10 inhibits only TAP-1 and LMP-7 transcription in CNE-1 cells. Taken together, these results suggest that the inhibition of NF-κB activity may be an important mechanism for vIL-10 suppression of APM (TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I) gene transcription in CNE-2 cells.
ABSTRACT
The human leukocyte antigen (HLA)-I and antigen-processing machinery (APM) are crucial in the anti-cancer immune response. The aim of this study was to assess the clinical significance of the APM components [transporters associated with antigen processing (TAP)-1 and -2 and HLA-I] in nasopharyngeal carcinoma (NPC). A total of 58 NPC specimens and 20 healthy specimens used as control were evaluated by semiquantitative immunohistochemistry for three APM components (TAP-1, TAP-2 and HLA-I). The expression of the APM components in NPC was downregulated. CD4+ and CD8+ T cells were measured by flow cytometry and IL-10 was measured by ELISA. The number of CD8+ T cells and the expression of IL-10 were higher and the number of CD4+ T cells was lower in NPC, compared to the controls. The number of CD8+ T cells and the expression of IL-10 were negatively correlated with TAP-1, TAP-2 and HLA-I expression. The clinical phase, lymph node metastasis, distant metastasis, pathological type, TAP-1 expression, TAP-2 expression and HLA-I expression were identified as prognostic factors by the Kaplan-Meier analysis. A multivariate analysis using a Cox regression model indicated that distant metastasis and the downregulation of HLA-I expression were independent unfavorable prognostic factors. In conclusion, the lower expression of HLA-I induced immunosuppression in NPC patients and was associated with a poor prognosis.
ABSTRACT
OBJECTIVE: To study the anatomy and preparation methods of an improved lateral arm free flap (LAFF) for the future clinical application. METHODS: Twenty-two adult upper extremities from cadavers after injected with red latex through common carotid arteries were used. The course, branches, distribution and variations of the blood vessels and nerves of the improved LAFF were observed. The outer diameters of the vessels were measured. RESULTS: The mean length of vascular pedicle of the improved LAFF was (14.85 ± 1.28) cm, significantly more than that (5.46 ± 2.60) of traditional LAFF (t = -8.483, P < 0.001). The mean outer diameters of pedicle arteries and veins in the improved LAFF were (2.24 ± 0.66) mm and (2.22 ± 0.52) mm, significantly more than those (1.15 ± 0.21 and 1.26 ± 0.23) in traditional LAFF (t = -8.690, P < 0.001; t = -15.057, P < 0.001), respectively. CONCLUSION: The improved LAFF has a longer vascular pedicle and larger artery and vein in diameter than conventional LAFF, and is more suitable for the repair of the small and medium-sized defects of the head and neck.
Subject(s)
Free Tissue Flaps/blood supply , Free Tissue Flaps/innervation , Skin/anatomy & histology , Adult , Arm/anatomy & histology , Humans , Plastic Surgery Procedures , Skin TransplantationABSTRACT
OBJECTIVE: To explore the feasibility of endoscope-assisted thyroidectomy with minimal neck incision. METHODS: Endoscope-assisted thyroid surgeries had been accomplished through incision above sternal notch and in submental area respectively from August 2003 to August 2005, including 11 partial lobectomy, 3 lobectomy, 2 two-sides partial lobectomy, 1 isthmectomy. RESULTS: In this group, 12 cases approached through above sternal notch, 5 cases approached through the submental area, and all were successful. The mean length of incisions was 2.3 cm (range from 1.5 cm to 3.0 cm). No one was converted to open surgery. The mean time of operation was 61.3 minutes (range from 30 minutes to 120 minutes). The mean volume of hemorrhage during the operation was 15.6 ml (range from 10 to 40 ml). The mean volume of drainage of post-operation was 22.5 ml (range from 6 ml to 40 ml). The mean length of stay was 4. 5 days (range from 3 days to 6 days). There were no hoarseness and no low serum calcium. Following visits were performed after operation from 1 month to 12 months, and there were no stiff feelings on skin. The cosmetic outcomes of the incisions were good, except 1 case for scar physique. CONCLUSIONS: Endoscope-assisted thyroidectomy was safe and feasible with good cosmetic outcome. The selection of approach with minimal incision depends on the location of neoplasm.
