ABSTRACT
Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors and mainly invade the sphenoid, cavernous sinus or dura mate. Aberrant regulation of the Wnt signaling pathway plays an important role in tumorigenesis. This study was designed to investigate the relationships between secreted frizzled-related proteins (sFRPs), WIF1 genes and the invasion of NFPAs by tissue microassays (TMAs) of samples from 163 patients. Significantly weaker staining of WIF1 and sFRP4 were detected in the invasive group compared with the non-invasive group by TMAs (pâ¯=â¯0.002, pâ¯<â¯0.001). Univariate analysis showed a significant correlation between tumor invasion and low expression of WIF1 and sFRP4 (pâ¯=â¯0.002, pâ¯<â¯0.001). A similar trend was observed when analyzing the mRNA and protein levels through RT-PCR and western blot experiments. Methylation of the WIF1 promoter was significantly increased in invasive NFPAs compared with the noninvasive group (pâ¯=â¯0.004). The average progression free survival time in the high WIF1 group was longer than that in the low WIF1 group (pâ¯=â¯0.025). Furthermore, RT-PCR measured the levels of 11 miRNAs targeting WIF1 according to the Targetscan database and PubMed. The levels of miRNA-137, miRNA-374a-5p and miRNA-374b-5p in the invasive group were 0.037-fold, 0.577-fold and 0.44-fold that of the noninvasive group (pâ¯=â¯0.003, pâ¯=â¯0.049 and pâ¯=â¯0.047). Overexpression of miRNA-137 could inhibit the proliferation and invasion of GH3 cells through cell viability and Transwell experiments (pâ¯<â¯0.05). Furthermore, the WIF1 level was upregulated after overexpression of miRNA-137 compared with miRNA-137-NC (control miRNA) in GH3 cells. Our data suggest that WIF1 may be potential biomarker for the aggressiveness of NFPAs. miRNA-137 plays an important role in the Wnt signaling pathway by affecting promoter methylation of WIF1.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Adenoma/genetics , Gene Expression Regulation, Neoplastic , Genes, Neoplasm , Pituitary Neoplasms/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adenoma/pathology , Adult , Aged , Cell Line, Tumor , Cell Proliferation/genetics , DNA Methylation/genetics , Female , Humans , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Middle Aged , Neoplasm Invasiveness , Pituitary Neoplasms/pathology , Progression-Free Survival , Promoter Regions, Genetic , Proto-Oncogene Proteins/metabolism , Repressor Proteins/metabolism , Up-Regulation/genetics , Young AdultABSTRACT
Objective To investigate the effect of ganoderic acid A( GA-A) on apoptosis, invasion and KDR expression of human U251 cells.Methods Ganoderic acid A( GA-A) was prepared, human U251 cells were treated with 0.1, and 0.5 mmol/L GA-A, and the experiment was divided into blank control, low concentration and high concentration group.The expressions of KDR mRNA and KDR protein was assayed by RT-PCR and Western blot.The effect of GA-A on the proliferation and invasion capability of U251 cells was determined by CCK-8 and transwell assay in vitro, respectively.Flow cytometry was used to detect the influence of GA-A on the cell cycle and apoptosis of U251 cells, and TUNEL staining was detected the cell apoptosis too.Results Compared with the control group, KDR mRNA and protein expression of high concentration and low concentration group were significantly decreased(P <0.05), GA-A can significantly reduce the cell growth rate, reduce the proportion of cells in G1 phase and increase the proportion of S phase and G2 /M phase,cells apoptosis was significantly increased in the high concentration and low concentration group ( P <0.01), and cells proliferation and invasion was significantly decreased (P <0.05).Compared with low concentration group, the high concentration group induce cell apoptosis and inhibit the expression of KDR more significant (P <0.05). Conclusions Ganoderma acid A can induce apoptosis in U251 cells, inhibit proliferation and invasion, and can inhibit the expression of KDR mRNA and protein, which may be one of the mechanisms of anti-tumor.
ABSTRACT
Objective To study the clinical effect of microsurgical surgery for the treatment of intracranial aneurysms in the acute phase. Methods 88 patients with intracranial aneurysm who were treated with the microscopic surgery in our hospital were selected as the research object. The prognosis was evaluated by Glasgow scale ( GOS) ,and the mortality rate during the follow-up period and postoperative complications were observed. Results All the patients received surgery success. The operation time was (60. 5 ± 20. 3) min,and the intraop-erative blood loss was (45. 2 ± 21. 5) mL. 12 months after operation,according to the GOS score of daily living ability,42 patients were of good prognosis and the other 46 cases were of poor prognosis. The good prognosis rate was 47. 7% and it is significantly higher than that of 3 months and 6 months after surgery. The difference was statistically significant (P<0. 05). There were 4 cases died among the 88 patients with a mortality of 4. 5%. Conclusion Using microsurgical treatment to treat intracranial aneurysms can receive good prognosis and low mortality rate. Complications were significantly improved after symptomatic treatment.
