Objective: To investigate the expression of p73 and to analyze its role in ovarian epithelial tumors. Methods: The expression of p73 protein in 20 cases of benign ovarian tumor,9 cases of borderline ovarian tumor and 31 cases of epithelial ovarian carcinoma was analyzed with immunohistochemical technique. Results: The expression of p73 was not positive in benign ovarian tumors(0/20), but positive expression was found in 2/9 (22.22%) of borderline trmors and 13/31 (41.94%) of primary ovarian epithelial malignant tumors. There were obvious differences of p73 expression among the three groups (P0.05). The expression of p73 was negatively correlated with the differentiation of malignant tumor (P0.05)and it had higher expression in cases of lower differentiation. There was no difference of p73 expression among cases with different differentiation (P0.05). Conclusion: p73 gene takes part in the development of ovarian epithelial tumors. It might play an important role in the genesis of ovarian cancer.
Abstract Background Biliary atresia (BA) is a severe cholangiopathy possibly resulting from virus-induced and immune-mediated injury of the biliary system. IFN-γ, secreted from CD4 + Th1 cells and CD8 + cytotoxic T cells, is a major mediator of liver pathology. Programmed death protein-1 (PD-1) signaling suppresses T cell function. However, how PD-1 modify T cell function in BA remains incompletely understood. Methods Frequencies of PD-1 expressing CD4 + and CD8 + T cells were analyzed in the liver and blood from BA and control subjects. Associations of PD-1 + CD4 + /CD8 + T cell abundances with liver function indices were measured. Function of PD-1 was measured by administration of an anti-PD-1 antibody in a Rhesus Rotavirus (RRV)-induced BA model. Survival, histology, direct bilirubin, liver immune cell subsets and cytokine production were analyzed. Results PD-1 was significantly upregulated in CD4 + and CD8 + T cells in patients with BA compared with control subjects. PD-1 expression in T cells was negatively associated with IFN-γ concentration in liver (PD-1 + CD4 + T cells in liver vs. IFN-γ concentration, r = − 0.25, p = 0.05; PD-1 + CD8 + T cells in liver vs. IFN-γ concentration, r = − 0.39, p = 0.004). Blockade of PD-1 increased IFN-γ expression in CD4 + T and CD8 + T cells (RRV vs. anti-PD-1 treated RRV mice: 11.59 ± 3.43% vs. 21.26 ± 5.32% IFN-γ + in hepatic CD4 + T cells, p = 0.0003; 9.33 ± 4.03% vs. 22.55 ± 7.47% IFN-γ + in hepatic CD8 + T cells, p = 0.0001), suppressed bilirubin production (RRV vs. anti-PD-1 treated RRV mice: 285.4 ± 47.93 vs. 229.8 ± 45.86 μmol/L total bilirubin, p = 0.01) and exacerbated liver immunopathology. Conclusions PD-1 plays a protective role in infants with BA by suppressing IFN-γ production in T cells. Increasing PD-1 signaling may serve as a therapeutic strategy for BA.
Abstract Positive cofactor 4 ( PC 4) participates in DNA damage repair and involved in nonhomologous end joining ( NHEJ ). Our previous results demonstrated that knockdown of PC 4 downregulated the expression of XRCC 4‐like factor ( XLF ) in esophageal squamous cell carcinoma. However, the mechanism how PC 4 regulates the expression of XLF remains unclear. Here, we found that knockdown of PC 4 increased radiosensitivity of non‐small cell lung cancer ( NSCLC ) both in vivo and in vitro. Furthermore, we found that PC 4 knockdown downregulated the expression of XLF , whereas recovering XLF expression restored radioresistance in the PC 4‐knockdown NSCLC cells. In addition, PC 4 knockdown inhibited XLF expression by transcriptionally suppressing of XLF . Moreover, PC 4 expression correlated with radiosensitivity and was an independent prognostic factor of progression‐free survival ( PFS ) in patients with NSCLC . These findings suggest that PC 4 could be used as a promising therapeutic target for NSCLC .
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