Wang D.,Shenyang University
European journal of medical research | Year: 2012
Accumulated evidence reveals that cyclooxygenase-2 (COX-2) was overexpressed in eutopic endometrium of endometriosis, which may play a critical role in the pathogenesis of endometriosis. However, few studies have been performed to explore the molecular mechanisms underlying the abnormal high expression of COX-2 in endometriosis. Considering the fact that a number of recent studies have shown DNA methylation affecting some genes in endometriosis, the present study was therefore aimed to determine whether the observed high expression COX-2 in endometriosis is caused by the hypomethylation of CpG island within the promoter of this gene. The endometrial tissues were collected from 60 women with endometriosis (endometriosis group) and 20 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation specific PCR. Quantitative real-time RT-PCR was performed to measure COX-2 mRNA level in endometrial tissues. The frequency of promoter hypermethylation of COX-2 was lower in eutopic endometrium of the endometriosis group (41.7%) than that in the control group (75.0%), P < 0.05. COX-2 mRNA level in the eutopic endometrium of the endometriosis group was 2.61-fold higher than that in the control group (P < 0.01). COX-2 mRNA level in unmethylated endometrium of the endometriosis group or the control group was 2.39-fold and 2.66-fold, respectively, higher than that in the methylated endometrium of the same group (P < 0.01). The hypomethylation within the promoter of COX-2 may be responsible for the elevated gene expression in eutopic endometrium of endometriosis.
Ma L.H.,Shenyang University
Journal of neurosurgery | Year: 2012
This study was undertaken to analyze outcomes in patients with newly diagnosed brain metastases from non-small cell lung cancer (NSCLC) who were treated with hypofractionated stereotactic radiotherapy (HSRT) with or without whole-brain radiotherapy (WBRT). One hundred seventy-one patients comprised the study population. Fifty-four patients received HSRT alone, and 117 patients received both HSRT and WBRT. The median survival time (MST) was determined using the Kaplan-Meier method. Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) were also used to evaluate the results. Univariate and multivariate analyses were performed to determine significant prognostic factors for overall survival. Tumor control, radiation toxicity, and cause of death in the HSRT and HSRT+WBRT groups were evaluated. The MST for all patients was 13 months. According to the Kaplan-Meier method, the probability of survival at 1, 2, and 3 years was 51.2%, 21.7%, and 10.1%. The MSTs for RPA Classes I, II, and III were 19, 12, and 5 months, respectively; and the MSTs for GPA Scores 4, 3, 2, and 1 were 24, 14, 12, and 6 months, respectively. The MSTs in the HSRT+WBRT and HSRT groups were 13 and 9 months (p = 0.044), respectively, for all patients, 13 and 8 months (p = 0.031), respectively, for patients with multiple brain metastases, and 16 and 15 months (p = 0.261), respectively, for patients with a single brain metastasis. The multivariate analysis showed that HSRT+WBRT was a significant factor only for patients with multiple brain metastases (p = 0.010). The Kaplan-Meier-estimated tumor control rates at 3, 6, 9, and 12 months were 92.2%, 82.7%, 79.5%, and 68.3% in the HSRT+WBRT group and 73.5%, 58.4%, 51.0%, and 43.3% in the HSRT group, respectively, in all 165 patients (p = 0.001). The estimated tumor control rates at 3, 6, 9, and 12 months were 94.3%, 81.9%, 79.6%, and 76.7%, respectively, in the HSRT+WBRT group and 77.8%, 61.4%, 52.6%, and 48.2%, respectively, in the HSRT group in the 80 patients harboring a single metastasis (p = 0.009). The estimated tumor control rates at 3, 6, 9, and 12 months were 90.5%, 83.5%, 79.5%, and 60.9%, respectively, in the HSRT+WBRT group and 68.2%, 54.5%, 48.5%, and 36.4%, respectively, in the HSRT group in the 85 patients with multiple metastases (p = 0.010). The toxicity incidences of Grade 3 or worse were 6.0% (7 of 117 patients) in the HSRT+WBRT group and 1.9% (1 of 54 patients) in the HSRT group (p = 0.438). The differences in neurological death rates between the HSRT+WBRT group and the HSRT group were not statistically significant (34.4% vs 44.7%, p = 0.125, in all patients; 30.0% vs 52.0%, p = 0.114, in patients with a single metastasis; and 38.0% vs 36.4%, p = 0.397, in patients with multiple metastases). The overall survival results in the present study were similar to those in other studies. Hypofractionated stereotactic radiotherapy provides an alternative method to traditional stereotactic radiosurgery. We suggest that WBRT should be combined with HSRT in patients with single or multiple newly diagnosed brain metastases from NSCLC.
Guo P.,Shenyang University
PloS one | Year: 2013
Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors, which may play a vital role in carcinogenesis. However, there is no study investigating the relationship among Legumain expression, clinicopathologic, biological variables and patient prognosis in gastric carcinoma. In this study, a tissue microarray (TMA) containing 282 samples of primary gastric cancer was assessed for Legumain expression by immunohistochemistry. The TMA included 98 lymph node metastasis samples. The protein expression levels of Legumain were evaluated by Western blot analysis. Cytoplasmic immunoreactivity of Legumain was over-expressed in gastric cancer compared with paired normal gastric mucosa. Increased Legumain levels were significantly correlated with clinical stage, presence of distant metastasis. Legumain was significantly over-expressed in primary gastric cancer with metastasis than without metastasis. Patients with Legumain-positive localized tumors had lower 5-year overall survival (OS) than those with Legumain-negative tumors. Multivariate survival analysis showed that Legumain was an independent prognostic marker for OS (HR 1.459, 95% CI 1.251-1.703, P = 0.007). Legumain expression could serve as a prognostic biomarker in patients at risk of developing metastasis or recurrence with gastric carcinoma.
Song L.,Shenyang University
PloS one | Year: 2012
Silicosis is an occupational lung disease caused by inhalation of silica dust and characterized by lung inflammation and fibrosis. Previous study showed that Tregs regulate the process of silicosis by modulating the maintenance of immune homeostasis in the lung. Th17 cells share reciprocal developmental pathway with Tregs and play a pivotal role in the immunopathogenesis of many lung diseases by recruiting and activating neutrophils, but the regulatory function of Tregs on Th17 response in silica induced lung fibrosis remains to be explored. To evaluate the role of Th17 and IL-17 in the development of silicosis and their interaction with Tregs, Treg-depleted mice model was generated and exposed to silica to establish experimental model of silica-induced lung fibrosis. Here we showed that silica increased Th17 response in lung fibrosis. Tregs depletion enhanced the neutrophils accumulation and attenuated Th17 response in silica induced lung fibrosis. Both mRNA and protein results showed that Tregs exerted its modulatory function on Th17 cells and IL-17 by regulating TGF-β1 and IL-1β. Our study suggested that Tregs could promote Th17 cells differentiation by regulating TGF-β1 and IL-1β in silica induced lung fibrosis of mice, which further the understanding of the progress of silicosis and provide a new insight in the regulatory mechanism of Th17 by Tregs in lung inflammation.
Ma H.,Shenyang University
Journal of separation science | Year: 2012
A simple and efficient method based on cloud-point extraction combined with high-performance liquid chromatography was developed and validated for the determination of larotaxel in rat plasma. Nonionic surfactant Triton X-114 was chosen as the extraction solvent. Variable parameters affecting the cloud-point extraction efficiency, for example the nature and concentration of surfactant, NaOH concentration, incubation temperature, and time were evaluated and optimized. Chromatographic separation was accomplished on a Diamonsil C(18) column (150 mm × 4.6 mm, 5 μm) using a mobile phase consisting of acetonitrile and 0.1% phosphoric acid with pH 4.0 (60:40, v/v). The calibration curve showed good linearity over the range of 0.05-10 μg/mL. Under the optimum conditions, the method was shown to be reproducible and reliable with intraday precision below 5.7%, interday precision below 7.2%, accuracy within ±3.5%, and mean extraction recovery of 91.8-94.2%. The validated method was successfully applied to the pharmacokinetic study of larotaxel in rat plasma after a single intravenous administration of larotaxel injection and larotaxel-loaded liposome, respectively. The results indicated that the larotaxel-loaded liposome led to significant differences in pharmacokinetic profile. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.