Zhang H.-Y.,General Hospital of Beijing Military Area |
Liang F.,Surgery Academy |
Jia Z.-L.,General Hospital of Beijing Military Area |
Song S.-T.,Affiliated Hospital of Academy of Military Medical science |
Jiang Z.-F.,Affiliated Hospital of Academy of Military Medical science
Oncology Letters | Year: 2013
The tumor suppressor gene, PTEN, has previously been demonstrated to be involved in breast tumorigenesis and tumor progression. The aim of the present study was to investigate the expression and significance of PTEN in breast carcinomas, to detect the mutation frequency of PTEN in sporadic breast carcinoma tissues and to determine the association between PTEN promoter methylation and gene expression. Immunohistochemical methods were used to analyze the expression of the PTEN gene in 146 cases of breast carcinoma and 10 cases of normal breast tissue closely adjacent to the carcinoma. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis was used to analyze conformation polymorphisms in 45 breast carcinoma and 10 normal breast tissues. Point mutations of abnormal single stranded conformation were detected by DNA sequencing. The methylation of the PTEN promoter was analyzed by methylation-specific PCR. Expression of PTEN was detected in 57.5% (84/146) of patients with breast carcinoma. By contrast, PTEN expression was detected in 100% of normal samples. Expression of PTEN was found to negatively correlate with the tumor size, the pathological stage and the expression of the estrogen receptor (ER) and the progesterone receptor (PR) in breast cancer. The 2-year disease-free survival of patients with a high expression of PTEN was higher compared with those with low PTEN expression (P<0.05). Missense mutations in exon 2 of PTEN were identified in 1/45 breast cancer cases. PTEN promoter methylation was detected in 31.1% (14/45) of breast carcinomas, of which 64.3% (9/14) were associated with a loss of PTEN expression. The tumor suppressor gene, PTEN, was abnormally expressed in the breast carcinomas. The number of PTEN mutations were low (1/45) in the sporadic breast cancer cases analyzed in the present study and PTEN promoter methylation may have been the main mechanism leading to the decreased expression of PTEN. These results indicate that PTEN is important for the tumorigenesis, development and prognosis of breast cancer.
Zhang X.-G.,General Hospital of Beijing Military Area |
Zhang Y.-Q.,China National Institute of Standardization |
Zhao D.-K.,General Hospital of Beijing Military Area |
Wu J.-X.,General Hospital of Beijing Military Area |
And 4 more authors.
European Review for Medical and Pharmacological Sciences | Year: 2014
OBJECTIVE: To evaluate the relationship between blood glucose fluctuation and macrovascular dysfunction. PATIENTS AND METHODS: Eighty-eight type 2 diabetes mellitus (T2DM) patients with or without coronary heart disease (CHD) and 30 healthy control subjects were recruited. Glycosylated hemoglobin A1c (HbA1c), fasting insulin (FIns), and Creaction protein (CRP) and some other general clinical variables were measured. A 72-hour continuous glucose monitoring (CGM) and brachial artery endothelium-dependent flow-mediated dilation (FMD) assessment were performed. The glucose excursion, MAGE (mean amplitude of glycemic excursions), LAGE (largest amplitude of glycemic excursions), MPPGE (mean postprandial glycemic excursions), MODD (absolute means of daily differences), and IAUC70 (incremental area under the curve below 70 mg/dl) during the CGM were analyzed. Correlations between the various variables were analyzed. RESULTS: Enhanced blood glucose fluctuation was observed in T2DM patients with CHD as compared to other participants. And blood glucose fluctuation was correlated with FMD, CRP and HOMA-IR. CONCLUSIONS: Blood glucose fluctuation is an important factor that affects inflammatory response and possibly induces CHD in T2DM patients.
PubMed | Affiliated Hospital of Academy of Military Medical science, General Hospital of Beijing Military Area and CAS Beijing Institute of Genomics
Type: | Journal: World journal of surgical oncology | Year: 2015
Non-sentinel lymph node (NSLN) status prediction with molecular biomarkers may make some sentinel lymph node (SLN) positive breast cancer patients avoid the axillary lymph node dissection, but the available markers remain limited.SLN positive patients with and without NSLN invasion were selected, and genes differentially expressed or fused in SLN metastasis were screened by next-generation RNA sequencing.Six candidates (all ER/PR+, HER2-, Ki-67 <20%) with metastatic SLNs selected from 305 patients were equally categorized as NSLN negative and positive. We identified 103 specifically expressed genes in the NSLN negative group and 47 in the NSLN positive group. Among them, FABP1 (negative group) and CYP2A13 (positive group) were the only 2 protein-encoding genes with expression levels in the 8th to 10th deciles. Using a false discovery rate threshold of <0.05, 62 up-regulated genes and 98 down-regulated genes were discovered in the NSLN positive group. Furthermore, 10 gene fusions were identified in this group with the most frequently fused gene being IGLL5.The biomarkers screened in present study may broaden our understanding of the mechanisms of breast cancer metastasis to the lymph nodes and contribute to the axillary surgery selection for SLN positive patients.
Cai X.,Chinese Institute of Basic Medical Sciences |
Wang J.,Chinese Institute of Basic Medical Sciences |
Wang Y.,Chinese Institute of Basic Medical Sciences |
Yang Y.,General Hospital of Beijing Military Area |
And 3 more authors.
Molecular Biology Reports | Year: 2010
Interleukin-22 (IL-22) is a member of the IL-10 family. Its potential in clinical use has been highlighted for its important roles in promoting antimicrobial defense and preventing epithelial damages. Previous studies have reported that IL-22 can be expressed using prokaryotic systems and purified from inclusion bodies, however the recovery rate was poor. To produce functional IL-22 with a high yield, human IL-22 was inserted into the eukaryotic expression vector pPICZαA and transformed into Pichia pastoris. The expression of recombinant human IL-22 (rhIL-22) was induced by methanol and accounted for about 85% of the total secreted proteins. A simple purification strategy was established to purify the rhIL-22 from the culture supernatant, yielding 100 mg/l at 90% purity by chromatography with a SP Sepharose FF column. Bioactivity analysis showed the purified rhIL-22 demonstrated a specific activity that was comparable with the commercial one. This study provides a new strategy for large-scale production of bioactive IL-22 for use in basic studies and therapeutic applications. © 2009 Springer Science+Business Media B.V.
PubMed | General Hospital of Beijing Military Area and Chinese Institute of Basic Medical Sciences
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2015
We analyzed the susceptibility of intestinal stromal tumors using cell culture and proteomics. Human SGC7901 gastric cells were selected and divided into a blank control group (untransfected SGC7901 cells), a negative control group [SGC7901 cells transfected with negative interference control-small interfering RNA (siRNA)], and a COOH-terminus tensin-like molecule (CTEN)-siRNA-1 group (SGC7901 cells transfected with CTEN-siRNA-1). The cells were successfully transfected and subjected to analyses of cell proliferation, cell cycle, cell invasion, CTEN expression, and proteomics. The percentages of cells in the G0/G1, S, and G2/M phases were similar in the three groups (P > 0.05), and the OD values were also similar at 24, 48, and 72 h (P > 0.05). Compared with the levels in the blank and negative control groups, CTEN protein in the CTEN-siRNA-1 group decreased by 66 and 65%, respectively, and significantly fewer cells in the CTEN-siRNA-1 group were capable of invasion (P < 0.05). Proteomic analysis showed that in the CTEN-siRNA-1 group, 283 proteins were upregulated and 242 were downregulated; from these, the expression levels of E-cadherin and ERK proteins changed significantly. Silencing the expression of CTEN in intestinal stromal tumor cells reduces their invasion capability. Moreover, silencing CTEN at different stages can also regulate the expression levels of E-cadherin and ERK proteins.
Wang L.-P.,General Hospital of Beijing Military Area
Chinese Journal of Pathology | Year: 2010
Objective To study the serrated lesions of colon and to compare the malignant potential between traditional serrated adenomas ( TSA ) and conventional adenomas (CAD). Methods A total of 5347 cases of colorectal polyps encountered in five regional hospitals during a five-year period were retrospectively reviewed. The serrated lesions were classified on the basis of histologic examination. One hundred and eighty-seven cases of CAD ( including 160 cases of tubular adenoma and 27 cases of villous adenoma) and 36 cases of invasive adenocarcinoma were randomly selected as the controls. The degree of dysplasia and expressions of Ki-67, p53 and beta-catenin in TSA and CAD were compared. Results Amongst the 5347 colorectal polyps studied, 258 cases (4.8%) of serrated lesions were found, which included 112 cases (43. 4%, 112/258) of hyperplastic polyp, 78 cases (30. 2% ,78/258) of TSA and 26 cases ( 10. 1% , 26/258 ) of sessile serrated adenoma. Sixty-two cases of TSA were identified from 3 hospitals, in which moderate dysplasia was found in 13 cases. High-grade intraepithelial neoplasia and ICA were found in 6 cases (9. 6% ). Compared with the 187 cases of CAD, moderate dysplasia were found in 27 cases and high-grade intraepithelial neoplasia and invasive adenocarcinoma were found in 25 cases ( 13. 3% , X = 19. 373 ,P = 0.000). There was statistically significant difference between TSA and CAD in the degree of dysphasia. The expression of Ki-67, p53 and beta-catenin in TSA and CAD showed no significant difference (P > 0.05 ) . Conclusions The incidence of serrated lesions is lower in northern Chinese population than that in Caucasians. TSA has obvious malignant potential; but the rate associated with highgrade intraepithelial neoplasia and invasive adenocarcinoma is lower than that in CAD.
Tian Y.,General Hospital of Beijing Military Area |
Liu Y.,Xi'an Jiaotong University |
He P.,Xi'an Jiaotong University |
Liu F.,Xi'an Jiaotong University |
And 7 more authors.
PLoS ONE | Year: 2014
Tetra-arsenic tetra-sulfide (As4S4) is an arsenic compound with anti-tumor activity, especially in acute promyelocytic leukemia (APL) that are resistant to retinoic acid (RA). Although recent studies revealed that the therapeutic action of As4S4 is closely associated with the induction of cellular apoptosis, the exact molecular mechanism of action of As4S4 in RA-resistant APL remains to be clarified. In this study, we found that As4S 4-induced apoptosis was accompanied by reduced mRNA and protein expression of SET gene in RA-resistant NB4-R1 cells. Moreover, RNAi knockdown of SET gene further promoted As4S4-induced apoptosis, while SET over-expression inhibited it, suggesting that As4S4 induces apoptosis through the reduction of SET protein in NB4-R1 cells. We also demonstrated that the knockdown of SET gene resulted in the upregulation of protein phosphatase 2 (PP2A) expression and the downregulation of promyelocytic leukemia and retinoic acid receptor α fusion gene (PML-RARα) expression, which were enhanced by As4S4 treatments. By contrast, over-expression of SET gene resulted in PP2A downregulation and PML-RARα upregulation, which were abolished by As4S4 pretreatment. Since PP2A is a pro-apoptotic factor and PMLRARα is an anti-apoptotic factor, our results suggest that As4S 4-induced apoptosis in NB4-R1 cells is through the downregulation of SET protein expression, which in turn increases PP2A and reduces PML-RARα expressions to lead to cell apoptosis. © 2014 Tian et al.
Ding Y.,General Hospital of Beijing Military Area |
Qiu L.,General Hospital of Beijing Military Area |
Xu Q.,General Hospital of Beijing Military Area |
Song L.,General Hospital of Beijing Military Area |
And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2014
Objective: To evaluate the relationship between the subtype of cells/cellular constituents (the density of T lymphocyte subsets, B lymphocyte, macrophages, and FOXP3 positive cells in 93 patients with meningioma, WHO grades I and II) in the tumor microenvironment and clinicopathological parameters (gender, age, tumor location, size, recurrence and pathological type) of meningioma. Methods: Immunohistochemical demonstrations of CD20 and CD4 lymphocytes, CD68, and FOXP3 expression were performed. In order to assess the densities of CD4, CD20, CD68 and FOXP3 positive cells in 93 meningioma patients, the results were derived from independent reviews by two pathologists. Chi-square test was used for independent samples. Results: There were no relationships between the CD4+, CD68+ cell subsets and patients' age, sex, tumor size, grade and the recurrence of tumor. However, patients with recurrence had a significantly higher density of CD20+ B cells compared to patients with no recurrence (P = 0.003). For the Foxp3+ cell subset, results showed us that more female patients had high density of Foxp3+ cells compared with male patients, while the opposite results were observed in the low density group (P = 0.009). Furthermore, the density of Foxp3+ cells was significantly correlated with the tumor size (P = 0.004) and the pathological types (P = 0.004). Conclusion: Results in this study demonstrate that higher CD20+ B cell density in the tumor is associated with lower tumor recurrence and the density of Foxp3+ cells is significantly correlated with the patients' sex, tumor size and the pathological types. The results also suggest that understanding of the cellular constituents of tumors and the tumor microenvironment may help investigate the tumor pathogenesis and immunotherapies in meningioma.
Wang J.,General Hospital of Beijing Military Area |
Wang L.-P.,General Hospital of Beijing Military Area |
Xu S.,General Hospital of Beijing Military Area |
Yang G.-Z.,General Hospital of Beijing Military Area
Chinese Journal of Pathology | Year: 2013
Objective: To study the clinicopathologic features and differential diagnosis of proximal gastric mucosa and mucosa of Barrett's esophagus (BE) in biopsy specimens. Method: Thirty-eight cases of Barrett's esophagus (diagnosed using WHO criteria) and 44 cases of proximal gastric mucosa were studied by immunohistochemistry (for CK7, CK20, CK4, CK8, S-100 protein, MUC6, COX2 and bcl-2) and fluorescence in-situ hybridization (FISH) (for hTERC gene). The pathologic features were analyzed. Results: The differences in expression of CK7, CK20, MUC6, COX2 and bcl-2 between BE and proximal gastric mucosa with intestinal metaplasia were not statistically significant (P > 0. 05). There was however a statistically significant difference in expression of S-100 protein (P < 0. 05). The expression of CK7/CK4 and CK7/CK8 in BE showed positive correlation (P < 0.05). However, such correlation was not demonstrated in proximal gastric mucosa (P > 0. 05). The results of hTERC gene expression by FISH showed a statistically significant difference between the two groups: 57. 9% (22/38) in BE and 13. 6% (6/44) in proximal gastric mucosa (P < 0. 05). Conclusions: The significance of CK7 and CK20 expression is uncertain in the differential diagnosis between BE and proximal gastric mucosa. On the other hand, positivity for CK7/CK4/CK8 may support the diagnosis of BE and play a role in distinguishing between the two groups. S-100 protein expression and detection of hTERC gene amplification also contribute to the diagnosis of BE.
PubMed | General Hospital of Beijing Military Area and PLA Fourth Military Medical University
Type: Journal Article | Journal: Journal of periodontology | Year: 2016
Human periodontal ligament stem cells (PDLSCs) display efficient osteogenic differentiation capacity but fail to rescue bone breakdown associated with periodontitis. Endoplasmic reticulum (ER) stress and the unfolded protein response have recently been linked to inflammation and osteogenic differentiation. Therefore, the role of the double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK) pathway in the impaired osteogenic differentiation ability of PDLSCs treated with tumor necrosis factor (TNF)- was investigated.PDLSCs were isolated and stimulated with osteogenic media containing 1, 10, or 20 ng/mL TNF-. Assessment included: 1) expression of runt-related transcription factor 2 and osteocalcin; 2) mRNA expression and activity of alkaline phosphatase; and 3) formation of mineralization nodules. Furthermore, expression of PERK pathway-related factors: 1) glucose-regulated protein (GRP) 78; 2) PERK; 3) activating transcription factor (ATF) 4; and 4) CCAAT-enhancer-binding proteins (C/EBP) homologous protein were also measured. Osteogenic differentiation and inhibition of the PERK pathway were also examined in cells pretreated with an inhibitor of ER stress, 4-phenylbutyric acid (PBA), followed by TNF- stimulation. Finally, PERK small interfering RNA was used to examine osteogenic differentiation attenuated by TNF-.Higher concentrations of TNF- (10 and 20 ng/mL) impaired osteogenic differentiation of PDLSCs but activated the PERK pathway. Pretreatment of PDLSCs with lower concentrations of 4-PBA prevented the TNF--induced upregulation of GRP78, PERK, and ATF4 and recovered differentiation ability. Finally, PERK knockdown also restored osteogenic differentiation.TNF- attenuates osteogenic differentiation ability of PDLSCs through activation of the PERK pathway.