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Cheng Z.-D.,Anhui Medical University | Hu S.-L.,Anhui Medical University | Sun Y.-B.,Anhui Province Hospital | Xu W.-P.,Anhui Evidence based Medicine Center | And 2 more authors.
Chinese Journal of Cancer | Year: 2010

Background and Objective: Transcriptional silencing induced by CpG island methylation is believed to be one of the important mechanisms of carcinogenesis. Checkpoint with fork head-associated and ring finger (CHFR) governs the transition from prophase to prometaphase in response to mitotic stress. This study was to analyze the relationship between the methylation of CHFR gene and the clinicopathologic features of gastric cancer, and the difference of results between methylation- specific polymerase chain reaction (MSP) and combined bisulfite restriction analysis (COBRA) in detecting aberrant methylation of CHFR gene in gastric cancer. Methods: Both MSP and COBRA methods were used to detect the promoter methylation of CHFR gene in gastric cancer specimens from 64 patients. The relationship between methylation status of CHFR gene and the clinicopathologic features of gastric cancer were analyzed using SPSS16.0. Results: The methylation rates of CHFR gene promoter were significantly higher in gastric cancer samples than in the corresponding paracancer normal gastric mucosa by MSP (51.6% vs. 18.8%, P < 0.001). However, there was no significant correlation between methylation status of CHFR gene and the clinicopathologic parameters of gastric cancer, including age, gender, tumor size, clinical stage, Borrman type, tumor Invasion depth, differentiation, and lymph node metastasis (P > 0.05). Aberrant methylation of the CHFR gene was detected in 27 (42.2%) of the 64 specimens of gastric cancer using COBRA, which did not significantly differ from that using MSP (P > 0.05). Conclusions: Aberrant methylation of the CHFR gene is a frequent event in the carcinogenesis of gastric cancer. Detecting the methylation of CHFR gene In gastric mucosa may conduce to the diagnosis of gastric cancer. No difference was found between MSP and COBRA in detecting promoter methylation of CHFR gene in gastric cancer.


Hu S.-L.,Anhui Medical University | Huang D.-B.,Anhui Medical University | Sun Y.-B.,Anhui Medical University | Wu L.,Anhui Evidence based Medicine Center | And 5 more authors.
Medical Oncology | Year: 2011

Runx3 and CHFR genes were defined as tumor suppressor genes in gastric cancer (GC) recently. This paper was to investigate the roles of methylation and expression status of Runx3 and CHFR genes in GC patients. Methylation-specific polymerase chain reaction (MSP) and bisulfite DNA sequencing (BSP) were used to detect methylation status of Runx3 and CHFR genes in GC patients. The expression of Runx3 and CHFR in GC patients was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical analysis. The expression of the protein and mRNA decreased remarkably in the patients with aberrant promoter methylation of Runx3 and CHFR genes. The methylation status of Runx3 and CHFR were inversely related to the tumor size, tumor invasion depth and tumor differentiation in GC patients. Moreover, the protein expression of Runx3 and CHFR were significantly correlated with tumor invasion depth and tumor differentiation, respectively. Aberrant promoter methylation of Runx3 and CHFR genes may be involved in the carcinogenesis and development of GC and may provide useful clues for the prediction of the malignant behaviors of GC. © 2010 Springer Science+Business Media, LLC.


Fang Z.-L.,Anhui Medical University | Shen G.,Anhui Evidence Based Medicine Center | Hu S.-L.,Anhui Medical University | Hu S.-L.,Anhui Evidence Based Medicine Center | And 4 more authors.
Chinese Journal of Evidence-Based Medicine | Year: 2011

Objective To assess the efficacy and safety of rosiglitazone in treating type 2 diabetes mellitus (T2DM) with essential hypertension (HBP). Methods Such databases as The Cochrane Library (Issue 4, 2009), PubMed (1970 to May 2010), CBM (1978 to May 2010), CNKI (1996 to May 2010), WanFang Database (1999 to May 2010), VIP (1996 to May 2010), and Google Scholar were searched on computer, and the relevant journals such as Chinese Journal of Diabetes Mellitus were also hand researched to investigate references and collect randomized controlled trials (RCTs) about rosiglitazone (experimental group) compared with non-rosiglitazone (control group) in treating T2DM with HBP. The data were extracted according to the inclusion and exclusion criteria by two reviewers independently, the quality of the included studies was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0, and meta-analysis was conducted by using RevMan 5.0 software. Results Among 10 RCTs involving 738 patients, one was in English from Greece, while nine were in Chinese. The average score quality of the included studies was in C level. The results of meta-analyses showed that the experimental group was more effective than the control group in lowering blood pressure levels (SBP: WMD= -17.83 mmHg, 95%CI -27.63 to -8.02; DBP: WMD=-7.81 mmHg, 95%CI -10.18 to -5.44), blood glucose levels (FBG: WMD= -1.66 mmol/L, 95%CI -3.08 to -0.23; PBG: WMD= -2.38 mmol/L, 95%CI - 4.12 to -0.64), triglyceride (TG) levels (WMD= -0.29 mmol/L, 95%CI -0.43 to -0.14), low-density lipoprotein cholesterol (LDL-C) levels (WMD= -0.76 mmol/L, 95%CI -1.02 to -0.50), insulin levels (FINS: WMD= -7.06 mU/L, 95%CI -9.47 to -4.65; PINS: WMD= -98.86 mU/L, 95%CI -116.38 to -81.34), glycosylated hemoglobin (HbA1c) levels (WMD=-0.75%, 95%CI -1.07 to -0.42), and insulin resistance index (HOMA-IR) (WMD= -1.61, 95%CI -2.18 to -1.05); the experimental group was more effective than the control group in increaseing the high-density lipoprotein cholesterol levels (HDL-C) (WMD=0.21 mmol/L, 95%CI 0.12 to 0.30), and insulin sensitivity index (ISI) (WMD=1.64, 95%CI 1.48 to 1.80); the therapeutic effect for hypertension was greater in the experimental group than in the control group (OR=9.35, 95%CI 4.76 to 18.35); there were no significant differences in cholesterol levels (TC) (WMD= -0.22 mmol/L, 95%CI -0.55 to 0.10), body mass index (BMI) (WMD= -0.26 kg/m2, 95%CI -0.86 to 0.33), heart rates (HR) (WMD=0.50 bpm, 95%CI -4.98 to 5.98), and urine albumin excretion (UAE) (WMD= -16.00mg/24h, 95%CI -37.90 to 5.90); additionally, there were also no significant differences in adverse reactions between the two groups, such as edema (OR=3.01, 95%CI 0.62 to 14.54), gastrointestinal discomfort (OR=1.19, 95%CI 0.63 to 2.24), headache and fatigue (OR=9.79, 95%CI 0.51 to 186.95), and anemia (OR=2.38, 95%CI 0.09 to 59.90). Conclusion To treating patients suffering from T2DM with HBP, the rosiglitazone is much effective than the control group in lowering blood pressure, blood glucose and lipid, reducing insulin resistance and improving β-cell function. © 2011 Editorial Board of Chin J Evid-based Med.


Hu S.-L.,Anhui Medical University | Kong X.-Y.,Anhui Medical University | Cheng Z.-D.,Anhui Medical University | Sun Y.-B.,Anhui Province Hospital | And 6 more authors.
Tumori | Year: 2010

Aims and background. Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including gastric cancer. A number of reports on methylation of various genes in gastric cancer have been published, but most of these studies focused on cancer tissues or only a single gene. In this study, we determined the promoter hypermethylation status and mRNA expression of 4 genes: p16, Runx3, DAPK and CHFR. Methods. Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of p16, Runx3, DAPK and CHFR gene promoters in cancer and adjacent normal gastric mucosa specimens from 70 patients with gastric cancer, as well as normal gastric biopsy samples from 30 people without cancer serving as controls. In addition, them RNA expression of p16, Runx3, DAPK and CHFR was investigated in 34 gastric cancer patients by RT-PCR. Bisulfite DNA sequence analysis was applied to check the positive samples detected by MSP. Results. When carcinoma specimens were compared with adjacent normal gastric mucosa samples, a significant increase in promoter methylation of p16, Runx3, DAPK and CHFR was observed, while all 30 histologically normal gastric specimens were methylation free for all 4 genes. The methylation rate of the 4 genes increased from normal stomach tissue to tumor-adjacent gastric mucosa to gastric cancer tissue. Concurrent methylation in 2 or more genes was found in 22.9% of tumor-adjacent normal gastric mucosa and 75.7% of cancer tissues. No correlation was found between hypermethylation and other clinicopathological parameters such as sex, age, and tumor location. However, the frequency of DAPK and CHFR methylation in cancer tissues was significantly associated with the extent of differentiation and lymph node metastasis (P <0.05) and the frequency of Runx3 methylation was significantly associated with tumor size (P <0.05). Weak expression and loss of expression of the 4 genes was observed in cancer tissues and was significantly associated with promoter hypermethylation (P <0.05). Conclusions. Promoter hypermethylation of p16, Runx3, DAPK and CHFR is frequent in gastric cancer. DAPK and CHFR promoter hypermethylation may be an important help in evaluating the differentiation grade and lymph node status of gastric cancer. Weak gene expression and loss of gene expression due to promoter hypermethylation may be a cancer-specific event. Free full text available at www.tumorionline.it.


Shen J.-J.,Anhui Medical University | Hu S.-L.,Anhui Medical University | Hu S.-L.,Anhui Evidence Based Medicine Center | Shen G.,CPC Anhui Provincial Hospital Authorities Cadre Ward | And 4 more authors.
Chinese Journal of Cancer Prevention and Treatment | Year: 2010

OBJECTIVE: To evaluate the effectiveness and safety of lapatinib on the prognosis of HER-2 positive patients with metastatic and advanced breast cancer by meta-analysis. METHODS: Randomized controlled trials (RCTs) and quasi-RCTs in the following electronic databases: Pubmed, EMBASE, Cochrane library (Issue 2, 2010), CBM, CNKI, VIP, and Wanfang data base were searched. All the data were analyzed by Stata 10.0. RESULTS: Four studies involving a total of 1 028 participants met the inclusion criteria. The outcomes of meta-analysis implied that: Compared with adjuvant chemotherapy alone, lapatinib plus adjuvant chemotherapy could improve the time to progression, TTP (HR = 0.54, 95% CI: 0.44-0.66, P<0.001) and progession free survival, PFS (HR = 0.51, 95% CI: 0.34-0.76, P = 0.001); overall response rate, ORR (RR = 1.69, 95% CI: 1.33-2.14, P<0.001); clinical benefit rate, CBR (RR = 1.63, 95% CI: 1.34-1. 99, P<0.001). There were also statistical differences between the 2 therapies in diarrhea (RR = 2.07, 95% CI: 1.42-3. 02, P<0.001) and rash (RR = 2.31, 95% CI: 1.64-3.25, P = 0.007). CONCLUSIONS: Lapatinib plus adjuvant chemotherapy can improve the time to progression, progression free survival, overall response rate and clinical benefit rate. However, it also elevates the incidence rate of diarrhea and rash.

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