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Zhu W.,Yuhuangding Hospital of Yantai | Liu J.,Yuhuangding Hospital of Yantai | Zou P.,Yuhuangding Hospital of Yantai | Chen H.,Yuhuangding Hospital of Yantai
International Journal of Clinical and Experimental Medicine | Year: 2017

The methylation of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter is frequently observed in several cancer types. The potential correlation between the C>T allele at SNP rs16906252 and methylation in MGMT are being actively investigated and remain largely elusive. We studied the allelic pattern of MGMT methylation through meta-analysis. All eligible studies were identified by searching PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure Database. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixed- or random-effect model. Genotype and allelic frequency compared between cases and controls together with further subgroup analyses were carried out by cancer type. A total of 6 studies involving 1775 cancer cases were analyzed. Meta-analysis from this study indicated that the T allele of the rs16906252 SNP were strongly associated with increased risk for MGMT methylation in allelic model (OR = 9.70, 95% CI 4.12-22.86, Pheterogeneity = 0.021), heterozygote comparison OR = 11.28, 95% CI 4.46-28.52, Pheterogeneity = 0.024) and dominant model (OR = 6.61, 95% CI 3.23-13.54, Pheterogeneity = 0.003). Stratified analysis by cancer type indicated that the association became more prominent among glioblastoma, colorectal cancer and other cancer. Our study provides strong evidence that the T allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in cancer. Clarifying this association could advance our knowledge of the influence of MGMT promoter-enhancer single nucleotide polymorphism rs16906252 on MGMT promoter methylation in cancer. © 2017, E-Century Publishing Corporation. All rights reserved.


Zhang G.,Yantai University | Wang Y.,Chinese PLA 107 Hospital | Zhang Y.,Anhui Medical University | Wan X.,Anhui Agricultural University | And 17 more authors.
Current Molecular Medicine | Year: 2012

The purpose of this study was to test the hypothesis that administration of epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in widely consumed tea, inhibits cell proliferation, invasion, and angiogenesis in breast cancer patients. EGCG in 400 mg capsules was orally administered three times daily to breast cancer patients undergoing treatment with radiotherapy. Parameters related to cell proliferation, invasion, and angiogenesis were analyzed while blood samples were collected at different time points to determine efficacy of the EGCG treatment. Compared to patients who received radiotherapy alone, those given radiotherapy plus EGCG for an extended time period (two to eight weeks) showed significantly lower serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and reduced activation of metalloproteinase-9 and metalloproteinase-2 (MMP9/MMP2). Addition of sera obtained from patients treated with combination of radiotherapy and EGCG feeding for 2-8 weeks to in vitro cultures of highly-metastatic human MDA-MB-231 breast cancer cells resulted in the following significant changes: (1) suppression of cell proliferation and invasion; (2) arrest of cell cycles at the G0/G1 phase; (3) reduction of activation of MMP9/MMP2, expressions of Bcl-2/Bax, c-Met receptor, NF-κB, and the phosphorylation of Akt. MDA-MB-231 cells exposed to 5-10 μM EGCG also showed significant augmentation of the apoptosis inducing effects of γ-radiation, concomitant with reduced NF-κB protein level and AKT phosphorylation. These results provide hitherto unreported evidence that EGCG potentiated efficacy of radiotherapy in breast cancer patients, and raise the possibility that this tea polyphenol has potential to be a therapeutic adjuvant against human metastatic breast cancer. © 2012 Bentham Science Publishers.


PubMed | Chinese University of Hong Kong, Yuhuangding Hospital of Yantai, Shanghai JiaoTong University and Soochow University of China
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2014

Infection caused by bacteria is one of the crucial risk factors for tendon adhesion formation. Silver nanoparticles (AgNP)-loaded physical barriers were reported to be effective in anti-infection and anti-adhesion. However, high silver load may lead to kidney and liver damages. This study was designed for Ibuprofen (IBU)-loaded poly(L-lactide) (PLLA) electrospun fibrous membranes containing a low dosage of Ag to evaluate its potential in maintaining suitable anti-infection and good anti-adhesion effects. The in vitro drug release study showed a sustained release of Ag ions and IBU from the membrane. Inferior adherence and proliferation of fibroblasts were found on the Ag4%-IBU4%-loaded PLLA electrospun fibrous membranes in comparison with pure PLLA and 4% Ag-loaded PLLA membranes. In the antibacterial test, all Ag-loaded PLLA electrospun fibrous membranes prevented the adhesion of Staphylococcus aureus and Staphylococcus epidermidis. Taken together, these results demonstrate that Ibuprofen is effective in enhancing the anti-adhesion and anti-proliferation effects of 4% Ag-loaded PLLA fibrous membrane. The medical potential of infection reduction and adhesion prevention of Ag4%-IBU4%-loaded PLLA electrospun fibrous membrane deserves to be further studied.


PubMed | Nanjing Institute of Technology, Nanjing Medical University and Yuhuangding Hospital of Yantai
Type: | Journal: Scientific reports | Year: 2016

Preeclampsia is a common, pregnancy-specific disease and a major contributor to maternal and foetal morbidity and mortality. Some placental abnormalities, including deficient implantation, abnormal trophoblast cell function, and improper placental vascular development, are believed to lead to preeclampsia. The long noncoding RNA SPRY4-IT1 is more highly expressed in preeclamptic human placentas than in normal placentas. We assessed the role of epithelial-mesenchymal transition (EMT)-associated invasion and migration in HTR-8/SVneo trophoblast cells. Overexpression of SPRY4-IT1 suppressed trophoblast cell migration and invasion, whereas reduced expression of SPRY4-IT1 prevented the EMT process. Mechanistically, an RNA immunoprecipitation experiment showed that SPRY4-IT1 bound directly to HuR and mediated the -catenin expression associated with EMT in HTR-8/SVneo cells. Moreover, the expression levels of genes in the WNT family, such as WNT3 and WNT5B, were changed after transfection of HTR-8/SVneo with SPRY4-IT1. Together, our results highlight the roles of SPRY4-IT1 in causing trophoblast cell dysfunction by acting through the Wnt/-catenin pathway, and consequently in impairing spiral artery remodelling. These results suggest a new potential therapeutic target for intervention against preeclampsia.


PubMed | 1 Shandong Medical College, Shandong Cancer Hospital and Yuhuangding Hospital of Yantai
Type: Clinical Trial, Phase I | Journal: The British journal of radiology | Year: 2016

This Phase I study aimed to assess the safety and efficacy of concurrent selective lymph node (SLN) late-course accelerated hyperfractionated (LCAF) intensity-modulated radiotherapy (IMRT) and S-1 plus cisplatin (CDDP) for the locally advanced oesophageal squamous-cell carcinoma (ESCC).The total dose of SLN LCAF IMRT was 59.6Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy (CCRT) was administered as follows: CDDP 25mgm(-2) on Days 1-3 and Days 22-24; S-1 was applied in a de-escalating dosage with a decrement of 10mgm(-2) per day, from its full dose level of 80mgm(-2), orally twice daily on Days 1-14 and Days 22-35. We inferred the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended dose, according to adverse reaction during CCRT.Totally, 15 patients with ESCC with T2-4N0-1M0-1a were enrolled in Dose Level 1 (80mgm(-2)). In the initial five patients, two patients developed DLTs. As MTD was not reached, five additional patients were treated with the same dose level, and DLTs occurred in only one patient. Similar results were found in the last five patients. After CCRT, the objective response rates were 100% for primary tumours and 86.2% for metastatic lymph nodes, respectively. Totally, the observed Grade 3 toxicities during CCRT were leukopenia (20%), neutropenia (20%) and dermatitis (13.3%), and no Grade 4 toxicity occurred. The Kaplan-Meier-estimated overall and progression survival rates were 86.7% and 66.7% (1 year), 73.3% and 60% (2 years) and 73.3% and 60% (3 years).The concurrent SLN LCAF IMRT and chemotherapy with S-1 and CDDP was well tolerated and showed promising efficacy. The dose of S-1 in this regimen was recommended with 80mgm(-2) orally twice daily on Days 1-14 and Days 22-35.CCRT with S-1 plus CDDP exhibited encouraging results with milder toxicities, high objective response rates and ideal overall survival time.


Sun Y.,Yuhuangding Hospital of Yantai
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2013

Research for surgical methods and experience of sinus fibrous dysplasia treatment by auxiliary nasal endoscopy image navigation. Retrospective analysis of the records of 4 patients from March 2006 to December 2011 who were diagnosed as fibrous dysplasia of nasal sinuses, 2 male and 2 female, aged from 19 yrs to 55 yrs and average age was 38 yrs; 3 of them were destroyed of sinus floor, the other who had the bone fiber of sphenoidal sinus. By using 16 multi slice spiral CT and 3D reconstruction, the 4 cases were all treated by drill grinding abnormal fibrous tissue in the nasal sinus cavities with auxiliary nasal endoscopy image navigation, to achieve contour in the bone fiber cavities. Lesions of 4 cases were accurately found and grinded under auxiliary nasal endoscopy image navigation. For 3 patients, headache, nasal congestion, facial discomfort and other symptoms have gradually disappeared after operation. However, one patient with sinus floor destroyed suffered facial swelling and pain 3 month after operation, with ineffective conservation treatment outcomes. After CT re-scan, it showed that there were a large number of bone residue in maxillary sinus during the re-operation. The reason was that the surgical cavity was not rinsed off which leaded to maxillary sinus congestion. With the methods of expansion of the maxillary sinus, flushing the cavity, and postoperative nasal and maxillary sinus rinse, symptoms disappeared 1 month later without recurrence. Patients with fibrous dysplasia of nasal sinuses are treated thoroughly, securely, and effectually, by drill grinding abnormal fibrous tissue in the nasal sinus cavities with auxiliary nasal endoscopy image navigation, to achieve contour in the bone fiber cavities.


Zhao W.,Yuhuangding Hospital of Yantai | Bian Y.,Yuhuangding Hospital of Yantai | Zhu W.,Yuhuangding Hospital of Yantai | Zou P.,Yuhuangding Hospital of Yantai | Tang G.,Yuhuangding Hospital of Yantai
Tumor Biology | Year: 2014

Regulator of telomere elongation helicase 1 (RTEL1) is critical for genome stability and tumor avoidance. Many studies have reported the associations of RTEL1 rs6010620 with glioma risk, but individually published results were inconclusive. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship. The PubMed, Embase, and Web of Science were systematically searched to identify relevant studies. The odds ratio (OR) and 95 % confidence interval (95 % CI) were computed to estimate the strength of the association using a fixed or random effects model. Ten studies were eligible for meta-analysis including data on glioma with 6,490 cases and 9,288 controls. Overall, there was a significant association between RTEL1 rs6010620 polymorphism and glioma risk in all four genetic models (GG vs. AA: OR=1.87, 95 % CI=1.60-2.18, Pheterogeneity =0.552; GA vs. AA: OR=1.30, 95 % CI=1.16-1.46, Pheterogeneity =0.495; dominant model-GG+GA vs. AA: OR=1.46, 95 % CI=1.31-1.63, Pheterogeneity =0.528; recessive model-GG vs. GA+AA: OR=1.36, 95 % CI=1.27-1.46, Pheterogeneity =0.093). Subgroup analyses by ethnicity showed that RTEL1 rs6010620 polymorphism resulted in a higher risk of glioma among both Asians and Caucasians. In the stratified analysis by ethnicity and source of controls, significantly increased risk was observed for Asians and Europeans in all genetic models, population-based studies in all genetic models, and hospital-based studies in three genetic models (heterozygote comparison, homozygote comparison, and dominant model). Our meta-analysis suggested that RTEL1 rs6010620 polymorphism is likely to be associated with increased glioma risk, which lends further biological plausibility to these findings. © 2014 International Society of Oncology and BioMarkers (ISOBM).


Xiu C.,Yuhuangding Hospital of Yantai | He Q.,Yuhuangding Hospital of Yantai | Zou P.,Yuhuangding Hospital of Yantai | Zhang H.,Yuhuangding Hospital of Yantai
International Journal of Clinical and Experimental Medicine | Year: 2016

X-ray cross-complementing group 4 (XRCC4) is crucial for cells to maintain genetic stability thereby inflicting carcinogenesis. To date, epidemiologic findings have reached conflicting and ambiguous conclusions on the role of XRCC4 rs1805377 polymorphism in cancer risks. We made a comprehensive quantitative evaluation by performing a meta-analysis. Eligible publications assessing the association between XRCC4 rs1805377 polymorphism and cancer risks from PubMed, Embase and China national knowledge infrastructure (CNKI) databases were indentified. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess association strengths with the fixed-effect model or the random-effects model dependent on the heterogeneity. At the same time, subgroup analysis and sensitivity analysis were conducted. A total of 8 studies including 1911 cases and 2688 controls were included based on the search criteria. It was revealed by this meta-analysis that, in the Asian population, there was significant correlation between XRCC4 rs1805377 polymorphism and the risk of cancers (GG vs. AA: OR = 1.28, 95% CI = 1.05-1.57, Pheterogeneity = 0.392). In further stratified analyses, XRCC4 rs1805377 polymorphism was associated with increased glioma risk among Asians in homozygote comparison (GG vs. AA: OR = 1.59, 95% CI = 1.12-2.25, Pheterogeneity = 0.261). Significantly elevated cancers risk were also observed in population-based studies (GG versus AA: OR = 1.38, 95% CI = 1.11-1.72, Pheterogeneity = 0.571) and using other method studies (GG versus AA: OR = 1.63, 95% CI = 1.11-2.39, Pheterogeneity = 0.275). This meta-analysis indicated that XRCC4 rs1805377 polymorphism probably was associated with gliomas susceptibility in Asians. © 2016, E-Century Publishing Corporation. All rights reserved.


Ma Z.-G.,Yuhuangding Hospital of Yantai
Journal of Leukemia and Lymphoma | Year: 2010

Objective: To study cytotoxic and antineoplastic effect in vitro of tephroseris kirilowii turez, houlub extract on U266 multiple myeloma cell line. Methods: U266 cells were cocultured with the tephroseris kirilowii turez, houlub extract. Cytotoxicity assay was used by CCK-8 detection kit. Cell cycle and apoptosis were determined using flow cytometry (FCM) analysis. Results: Extract of tephroseris kirilowii turez, houlub showed strong cytotoxicity against U266 cells.The IC 50 was about 3.2 mg/L. After exposure of U266 cells to the drug, the distribution of cell cycle was changed compared with that of the controls. When the durg concentration was 1.25, 2.5, 5 and 10 mg/L, respectively, the pencentages of cells in the G 0/G 1 phase were decreased with (34.12±0.49)%, (38.06±0.63)%, (27.46±0.61)%, (15.91±0.32)%, respectively, while those in the S phase were increased with (4.98±0.50)%, (4.01±0.22)%, (4.16±0.15)% and (5.04±0.12)% in G 2/M phase were increased with (50.05±1.12)%, (51.27±0.71)%, (51.84±0.73)% and (55.11±0.25)%, respectively, and apoptosis cells were increased. Apoptosis of U266 cells inadose-depadeut manner could be deteted with staining of Annexix V FITC/PI testing through FCM. Conclusion: Tephroseris kirilowii turez extract showed strong cytotoxic effect on U266 cells. The antineoplsastic mechanism of the drug can be partly due to its induced apoptotic effect.


PubMed | Yuhuangding Hospital of Yantai
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2014

Regulator of telomere elongation helicase 1 (RTEL1) is critical for genome stability and tumor avoidance. Many studies have reported the associations of RTEL1 rs6010620 with glioma risk, but individually published results were inconclusive. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship. The PubMed, Embase, and Web of Science were systematically searched to identify relevant studies. The odds ratio (OR) and 95 % confidence interval (95 % CI) were computed to estimate the strength of the association using a fixed or random effects model. Ten studies were eligible for meta-analysis including data on glioma with 6,490 cases and 9,288 controls. Overall, there was a significant association between RTEL1 rs6010620 polymorphism and glioma risk in all four genetic models (GG vs. AA: OR=1.87, 95 % CI=1.60-2.18, P heterogeneity=0.552; GA vs. AA: OR=1.30, 95 % CI=1.16-1.46, P heterogeneity=0.495; dominant model-GG+GA vs. AA: OR=1.46, 95 % CI=1.31-1.63, P heterogeneity=0.528; recessive model-GG vs. GA+AA: OR=1.36, 95 % CI=1.27-1.46, P heterogeneity=0.093). Subgroup analyses by ethnicity showed that RTEL1 rs6010620 polymorphism resulted in a higher risk of glioma among both Asians and Caucasians. In the stratified analysis by ethnicity and source of controls, significantly increased risk was observed for Asians and Europeans in all genetic models, population-based studies in all genetic models, and hospital-based studies in three genetic models (heterozygote comparison, homozygote comparison, and dominant model). Our meta-analysis suggested that RTEL1 rs6010620 polymorphism is likely to be associated with increased glioma risk, which lends further biological plausibility to these findings.

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