Yulan Zhao

Analysis of MiR-195 and MiR-497 expression, regulation and role in breast cancer

Purpose: To investigate expression, regulation, potential role and targets of miR-195 and miR-497 in breast cancer. Experimental Design: The expression patterns of miR-195 and miR-497 were initially examined in breast cancer tissues and cell lines by Northern blotting and quantitative real-time PCR. Combined bisulfite restriction analysis and bisulfite sequencing were carried out to study the DNA methylation status of miR-195 and miR-497 genes. Breast cancer cells stably expressing miR-195 and miR-497 were established to study their role and targets. Finally, normal, fibroadenoma and breast cancer tissues were employed to analyze the correlation between miR-195/497 levels and malignant stages of breast tumor tissues. Results: MiR-195 and miR-497 were significantly downregulated in breast cancer. The methylation state of CpG islands upstream of the miR-195/497 gene was found to be responsible for the downregulation of both miRNAs. Forced expression of miR-195 or miR-497 suppressed breast cancer cell proliferation and invasion. Raf-1 and Ccnd1 were identified as novel direct targets of miR-195 and miR-497. miR-195/497 expression levels in clinical specimens were found to be correlated inversely with malignancy of breast cancer. Conclusions: Our data imply that both miR-195 and miR-497 play important inhibitory roles in breast cancer malignancy and may be the potential therapeutic and diagnostic targets. Clin Cancer Res; 17(7); 1722–30. ©2011 AACR.

Prognostic role of microRNA-21 in various carcinomas: a systematic review and meta-analysis

Eur J Clin Invest 2011; 41 (11): 1245–1253

Prognostic role of C-reactive protein in breast cancer: a systematic review and meta-analysis

Background Recent studies have shown that C-reactive protein (CRP) may be associated with breast cancer. The purpose of this study is to summarize the predictive role of CRP for survival in breast cancer as shown in all available studies worldwide. Methods Related studies were identified and evaluated for quality through multiple search strategies. Data were collected from studies comparing overall, cancer-specific, and disease-free survival (OS, CSS, and DFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratios (HRs) of CRP for survival were calculated. Results A total of 10 studies (n=4,502) were included for this meta-analysis (9 for OS, 3 for CSS, and 3 for DFS). For overall and disease-free survival, the pooled HRs of CRP were significant at 1.62 (95% confidence interval [95% CI], 1.20-2.18) and 1.81 (95% CI, 1.44-2.26), respectively. For cancer-specific survival, the pooled HR in higher CRP expression in breast cancer was 2.08 (95% CI, 1.48-2.94), which could strongly predict poorer survival in breast cancer. Conclusions CRP has a critical prognostic value in patients with breast cancer as an inflammation biomarker.

Prognostic role of C-reactive protein and interleukin-6 in dialysis patients: a systematic review and meta-analysis.

Inflammation may be associated with mortality in dialysis patients. This study aims to summarize the prognostic value of two common inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6) for dialysis outcome. A total of 109 CRP studies and 22 IL-6 studies were identified from PubMed and EMBASE after systematic searching and assessment. The combined hazard ratios (HRs) of CRP and IL-6 for mortality were analyzed. For all-cause mortality (ACM), both CRP and IL-6 could significantly predict the outcome, with the pooled HRs of 1.142 (95%CI: 1.118-1.166) and 1.152 (95%CI: 1.094-1.214) for CRP and IL-6, respectively. For cardiovascular disease mortality (CVDM), the pooled HR of CRP (1.182, 95%CI: 1.134-1.232) was close to that of IL-6 (1.181, 95%CI: 1.068-1.307). Therefore, elevated levels of CRP or IL-6 were significantly associated with higher ACM and higher CVDM in dialysis patients. The predictive value of the inflammatory biomarkers may be useful in clinical practice.

Prognostic role of hormone receptors in ovarian cancer: a systematic review and meta-analysis.

Objective The aim of this study was to summarize the global predicting role of hormone receptors for survival in ovarian cancer. Methods Eligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall or progression-free/disease-free/relapse-free survival in patients with elevated levels of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) with those in patients with lower levels. Studies were pooled, and combined hazards ratios (HRs) of ER, PR, and HER2 for survival were calculated, respectively. Results A total of 35 studies were included for meta-analysis (23 for ER, 19 for PR, and 8 for HER2). For overall survival, the pooled HR of PR reached 0.88 [95% confidence interval (CI), 0.82-0.95], which means that elevated PR level could significantly indicate better survival. In contrast, elevated levels of HER2 could predict worse outcome with an HR of 1.41 (95% CI, 1.05–1.89). Increased level of ER was not significantly prognostic (HR, 0.94; 95% CI, 0.87–1.01). For progression-free survival/disease-free survival/recurrence-free survival, elevated PR level also had predictive value for better outcome with a pooled HR of PR of 0.80 (95% CI, 0.67–0.95). Oppositely, elevated HER2 level could predict poorer outcome with an HR of 1.55 (95% CI, 1.11–2.16). Estrogen receptor failed to predict outcome with an HR of 0.90 (95% CI, 0.78–1.03). Conclusions In patients with ovarian cancer, elevated level of PR predicted favorable survival, and elevated level of HER2 was associated with worse survival.

Sequential Responses to High-fat and High-calorie Feeding in an Obese Mouse Model

Objective: Reports on the immediate and long‐term responses to high‐fat and high‐calorie (HFC) feeding are controversial. Therefore, we examined the sequential effects of an HFC diet.

Impact of Serum Amyloid A on Tissue Factor and Tissue Factor Pathway Inhibitor Expression and Activity in Endothelial Cells

Objective—Although serum amyloid A (SAA) is a useful biomarker of coronary artery disease (CAD), its direct role in procoagulation is obscure. This study investigates the impact of SAA on the expression and activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in endothelial cells. Methods and Results—SAA was found to disturb the balance of TF and TFPI expression and activity in human endothelial cells. SAA (20 &mgr;g/mL) markedly induced TF expression between 4 to 8 hours in both protein and mRNA levels, as well as TF activity. Conversely, incubation of SAA (20 &mgr;g/mL) for 24 and 48 hours was found to significantly inhibit TFPI secretion, transcription, and activity. Pretreatment with formyl peptide receptor-like 1 (FPRL1) inhibitors (Pertussis toxin and WRWWWW) could block the SAA effects on TF and TFPI. Furthermore, pretreatment with the respective specific mitogen-activated protein kinase (MAPK) inhibitors (SB203580, PD98059, and SP600125) and NF&kgr;B inhibitor (Bay-11 to 7082) could block SAA-dependent TF induction. SAA also directly induced activation of MAP kinases and NF&kgr;B. Conclusions—The stimulating effect of SAA was faster-acting on the expression and activity of TF and the inhibitory effect was slower-acting on TFPI. The effects are mediated through FPRL1, MAP kinases and NF&kgr;B.

Prognostic role of microRNA-155 in various carcinomas: Results from a meta-analysis

BACKGROUND: Recent studies have shown that microRNAs (miRNA) have prognostic values in cancers. This meta-analysis seeks to summarize the global predicting role of miR-155 for survival in patients with a variety of carcinomas. METHODS: Eligible studies were identified through multiple search strategies. Data were extracted from studies investigating the relationship between miR-155 expression and survival in cancer patients. Combined hazard ratios (HRs) of miR-155 for outcome were analyzed. RESULTS: A total of 16 studies dealing with various carcinomas were included for this meta-analysis. For overall survival, higher miR-155 expression could significantly predict worse outcome with the pooled HR of 2.057 (95% CI: 1.392–3.039). For relapse or progress-free survival, elevated miR-155 was also a significant predictor, with a combined HR of 1.918 (95% CI: 1.311–2.806,). In addition, subgroup analysis showed that higher expression of miR-155 had the trends to predict worse outcome in lung cancer. However, the HRs did not reach the statistical significance. CONCLUSION: Our findings suggest that miR-155 detection has a prognostic value in cancer patients. Regularly measuring miR-155 expression may be useful in clinical practice.

Prognostic role of epidermal growth factor receptor in head and neck cancer: A meta‐analysis

To evaluate the predicting value of the epidermal growth factor receptor (EGFR) for survival in patients with head and neck cancer (HNC).

Celecoxib inhibits serum amyloid a-induced matrix metalloproteinase-10 expression in human endothelial cells.

Background: Although serum amyloid A (SAA) is an established biomarker of coronary artery disease (CAD), its direct role in matrix degradation is obscure. This study investigated the effect of SAA on the expression of matrix metalloproteinase-10 (MMP-10) in endothelial cells. The effect of celecoxib on SAA-dependent MMP-10 expression and its possible mediator were also investigated. Methods and Results: From our time course microarray screening, SAA (20 μg/ml) was found to increase MMP-10 mRNA expression over time (4–48 h) in human endothelial cells. Quantitative real-time PCR confirmed this transcriptional induction. Correspondingly, secreted MMP-10 protein was also markedly induced by SAA treatment for 24 h in a dose-dependent manner. We further examined cyclooxygenase-2 (COX-2) and its major product, prostaglandin E2 (PGE2), as possible mediators of MMP-10 induction. Direct PGE2 treatment could result in MMP-10 induction. Celecoxib, a selective COX-2 inhibitor, suppressed MMP-10 secretion induced by SAA. Conclusions: SAA induced MMP-10 expression and celecoxib prevented its induction. MMP-10 induction was at least partly mediated by PGE2.