Net platelet clot strength of thromboelastography platelet mapping assay for the identification of high on-treatment platelet reactivity in post-PCI patients.

High-on treatment platelet reactivity (HTPR) leads to more prevalence of thrombotic event in patients undergoing percutaneous coronary interventions (PCI). Dual antiplatelet therapy with aspirin in addition to one P2Y12 inhibitor is commonly administrated to reduce HTPR. However, 'one size fits all' antiplatelet strategy is widely implemented due to lacking benefits with tailored strategy. One reason for the failure of tailored treatment might be less specificity of the current indicators for HTPR. Therefore, searching for specific indicators for HTPR is critical. Thromboelastograph with platelet mapping (TEGpm) assay has been explored for identifying HTRP. Variables of TEGpm assay, including maximum amplitude (MA) induced by thrombin (MAthrombin), R time, platelet aggregation rate induced by ADP (TEGaradp) and MA induced by ADP (MAadp) have been demonstrated to be able to identify HTPR in post-PCI patients. However, these variables for HTPR might be less specific. Thus, in the present study, a novel variable nMAadp was derived by removing fibrin contribution from MAadp and analyzed for its usefulness in determining HTPR. In addition, MAthrombin, R time, MAadp and TEGaradp were also examined for determining HTPR. In conclusion, nMAadp and TEGaradp were demonstrated to be independent indicators for HTPR; nMAadp had the strongest power to identify HTPR with cutoff value of 26.3 mm; MAthrombin and R time were not significantly different between patients with and without HTPR; combination of TEGaradp and nMAadp further improved the ability to identify HTPR with an AUC of 0.893.

HDAC Inhibitor Attenuated NETs Formation Induced by Activated Platelets In Vitro, Partially Through Downregulating Platelet Secretion.

BACKGROUND: Accumulating studies in recent years have revealed that platelet activation is an important factor inducing neutrophil extracellular traps (NETs) formation in vivo, while the mechanism of this process is not fully elaborated, restricting its clinical use. Our previous study found that a histone deacetylase inhibitor (HDACi) could attenuate serum H3 elevation in septic mice, which was related to NETs formation, and others found HDAC6 to be involved in platelet activation, indicating that HDACis may attenuate platelet activation and result in reduced NETs formation. METHODS: Freshly isolated human platelets were activated by TRAP-6 with or without a HDACi, and secretion of α-granules was evaluated by testing PF4 in the supernatant using ELISA. NETs were induced by coincubating neutrophils with preactivated platelets, quantified by fluorescent intensity of Sytox green, monitored by live-cell imaging, and qualitatively analyzed by immunofluorescence. MAIN RESULTS: An in vitro bioreactive system to induce and monitor NETs formation using platelets and neutrophils was established. The PF4 elevation stimulated by TRAP-6 in the supernatant of platelets was attenuated by the HDACi, and NETs formation that was induced by coincubating neutrophils with the preactivated platelets was decreased in the presence of the HDACi. CONCLUSION: The HDACi attenuates NETs formation induced by activated platelets partially by modulating the secretion of platelets.

Establishment of thromboelastography reference intervals by indirect method and relevant factor analyses.

Thromboelastography (TEG) as a global coagulation test has been continuously developed for many decades in either research or clinical practice. The versatility of TEG test leads to difficulty in standardization and result interpretation. Reference intervals (RIs) of TEG may be one of the most controversial factors that influence its wide applications. RIs establishment with the traditional method is time-consuming and laborious as well as beyond general laboratory capability. Indirect method using stored data and with statistical calculation and small cost is emerging as an alternative approach for RIs determination. Gender, age, or both affect RIs and must be taken into account before RIs estimation. The present study retrospectively collected a total of 930 TEG results as subjects and established RIs with indirect method for Kaolin-activated TEG, including the parameters of R, K, αAngle, MA, and CI. Furthermore, gender, age, and gender-dependent age subsets analyses were performed to determine their effects on RIs of TEG. In this study, we found that TEG parameters showed more hypercoagulability in female than male, most of the measured TEG variables were significantly associated with aging, but only in male statistical significance was found among different age stratification and 60-year-old could be considered as cutting point to differentiate coagulation ability in male. In addition, RIs of TEG were estimated by indirect method suitably and verified to be valid in our study. Finally, the RIs of TEG by indirect method were basically significantly different to the RIs recommended by manufacturer, but the consistent percentage is relatively high in the most of measured parameters. In conclusion, it is suggestive that the indirect method for RIs establishment is feasible, but relevant factors, such as gender and age, specifically gender-dependent age effect, should be considered before RIs determinations.

Intercellular Adhesion Molecule-1 (ICAM-1) Polymorphisms and Cancer Risk: A Meta-Analysis.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) Lys469Glu (K469E) polymorphism and Gly 241Arg (G241R) polymorphism might play important roles in cancer development and progression. However, the results of previous studies are inconsistent. The aim of this study was to evaluate the association between ICAM-1 K469E and G241R polymorphisms and the risk of cancer by meta-analysis. METHODS: A comprehensive literature search (last search updated in November 2013) was conducted to identify case-control studies that investigated the association between ICAM-1 K469E and G241R polymorphisms and cancer risk. RESULTS: A total of 18 case-control studies for ICAM-1 polymorphisms were included in the meta-analysis, including 4,844 cancer cases and 5,618 healthy controls. For K469E polymorphism, no significant association was found between K469E polymorphism and cancer risk. However, subgroup analysis by ethnicity revealed one genetic comparison (GG vs. AA) presented the relationship with cancer risk in Asian subgroup, and two genetic models (GG+GA vs. AA and GA vs. AA) in European subgroup, respectively. For G241R polymorphism, G241R polymorphism was significantly association with cancer risk in overall analysis. The subgroup analysis by ethnicity showed that G241R polymorphism was significantly associated with cancer risk in European subgroup. CONCLUSION: ICAM-1 G241R polymorphism might be associated with cancer risk, especially in European populations, but the results doesn't support ICAM-1 K469E polymorphism as a risk factor for cancer.

The diagnostic accuracy of HE4 in lung cancer: a meta-analysis.

The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68-0.75), SPE 0.85 (95% CI: 0.81-0.88), PLR 4.68 (95% CI: 3.23-6.78), NLR 0.31 (95% CI: 0.24-0.39), and DOR 17.14 (95% CI: 9.72-30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future.

Serum galectin-3 as a potential marker for gastric cancer.

BACKGROUND: The identification of cancer biomarkers can advance the possibility for early detection and better monitoring of tumor progression. The aim of this study was to assess the diagnostic and prognostic value of serum galectin-3(Gal-3) in patients with gastric cancer (GC). MATERIAL AND METHODS: We measured serum Gal-3 levels using ELISA method in 87 patients with GC, 53 patients with benign gastric lesions, and 51 healthy controls. RESULTS: Serum levels of Gal-3 in patients with GC were significantly higher than those in benign disease patients and healthy controls (P<0.001), but no difference was found between benign disease patients and healthy controls (P=0.635). Additionally, serum Gal-3 level was associated with lymph node metastasis (P=0.001) and distant metastasis (P<0.001), whereas it was not related to gender (P=0.204), age (P=0.269), tumor size (P=0.399), location (P=0.715), TNM stage (P=0.385), differentiation (P=0.135), or invasion depth (P=0.273). The Kaplan-Meier survival analysis revealed that overall survival rates in patients with high Gal-3 levels were not significantly different that those with low Gal-3 levels (P=0.099). CONCLUSIONS: Results of the current study suggests that serum Gal-3 represents a potential diagnostic marker for patients with GC, and may be an adjunct to determine the individual prognosis of these patients.

IL-1α -889 C/T polymorphism and cancer susceptibility: a meta-analysis.

The -889 C/T polymorphism in the interleukin-1α (IL-1α) gene has been implicated in the risk of cancer, but the results are inconclusive. The present meta-analysis aimed to investigate the association between the -889 C/T polymorphism and cancer risk. A literature search in PubMed, Embase™, Web of Science™, Science Direct(®), SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases was carried out to identify studies investigating the association between IL-1α -889 C/T polymorphism and cancer risk. The odds ratio (OR) with 95% confidence interval (CI) were used to assess the strength of association. A total of 20 publications, involving 6,782 cases and 7,767 controls, were included in this meta-analysis. Combined analysis revealed a significant association between -889 C/T polymorphism and cancer risk under an allele model (OR =1.12, 95% CI =1.02-1.24, P=0.02), recessive model (OR =1.34, 95% CI =1.06-1.68, P=0.01), and homozygous comparison (OR =1.38, 95% CI =1.10-1.74, P<0.01). Subgroup analysis by ethnicity showed there was significant association between cancer risk and IL-1α -889C/T polymorphism in Asian populations under a recessive model (OR =2.57, 95% CI =1.11-5.98, P=0.03) and homozygous comparison (OR =2.60, 95% CI =1.12-6.04, P=0.03). Moreover, a subgroup analysis was conducted by source of control, and a statistically increased cancer risk was found in the hospital-based group, under a recessive model (OR =1.62, 95% CI =1.03-2.56, P=0.04) and homozygous comparison (OR =1.67, 95% CI =1.04-2.68, P=0.03). This meta-analysis suggests that IL-1α -889 C/T polymorphism contributes to cancer susceptibility. Further large and well-designed studies are needed to confirm this association.

Diagnostic role of circulating YKL-40 in endometrial carcinoma patients: a meta-analysis of seven related studies.

In the past decade, several studies have suggested a possible link between circulating YKL-40 levels and endometrial carcinoma (EC), but have arrived at inconsistent results. Therefore, we conducted the present meta-analysis and aim to disclose a more comprehensive evaluation of the sensitivity, specificity, and diagnostic accuracy of YKL-40 in EC. We systematically searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure databases for studies that evaluated the diagnostic value of YKL-40 in endometrial cancer. The STATA software 12.0 and Meta-Disc software were used to test the heterogeneity and to evaluate the overall test performance. A total of seven studies including 234 EC cases and 300 controls were included in our meta-analysis. The summary estimates of YKL-40 for EC diagnosis indicated a moderately high diagnostic accuracy for circulating YKL-40, with a sensitivity of 0.74, a specificity of 0.87, a PLR of 5.74, a NLR of 0.30, a DOR of 19.14, and an AUC of 0.80. On the basis of our meta-analysis, therefore, circulating YKL-40 could be promising and meaningful in the diagnosis of EC.

HBXIP expression predicts patient prognosis in breast cancer.

Emerging evidence demonstrated that hepatitis B virus X-interacting protein (HBXIP) has broad roles in cancers. The aim of the study is to investigate the association between HBXIP expression and clinicopathological features of breast cancer patients so as to determine whether HBXIP protein may be correlated with poor prognosis in breast cancer patients. HBXIP protein expression was assessed in a well-characterized series of breast cancer (n=196) with long-term follow-up, using immunohistochemistry method. Correlation between HBXIP expression and clinicopathological factors was analyzed. The effects of several variables on survival were tested by a Cox proportional hazards regression analysis. High HBXIP expression was predominantly observed in breast cancer tissues but not the adjacent normal breast tissues. The expression of HBXIP was high in 125 (63.8%) of the 196 cancer patients and low in 71 (36.2%) of the 196 patients, respectively. High HBXIP expression was positively correlated with TNM stage (P=0.001), lymph node metastasis (P<0.001), and Ki67 expression (P=0.002). The patients with high HBXIP expression had lower 5-year overall survival (OS) and disease-free survival (DFS) rates than those with low HBXIP expression as determined using the Kaplan-Meier method (OS: P=0.006; DFS: P=0.022). In Cox regression analysis, both HBXIP expression (P=0.002 and P=0.009, respectively) and lymph node metastasis (P<0.001 and P=0.008, respectively) were associated with poor OS and DFS. Our study suggested that high HBXIP is associated with the progression of breast cancer. HBXIP could be a valuable prognostic marker as well as a potential molecular therapy target for breast cancer patients.

The relationship between interleukin-18 polymorphisms and allergic disease: a meta-analysis.

Recent studies have suggested that IL-18 -607C/A and -137G/C polymorphisms may be associated with the risk of allergic disease; however, individually published results are inconclusive. Therefore, we performed a meta-analysis to clarify whether IL-18 -607C/A and -137G/C polymorphisms were associated with the risk of allergic disease. A total of 21 studies including 5,331 cases and 9,658 controls were involved in this meta-analysis. In the overall analysis and the subgroup analysis according to ethnicity, we did not find significant association between IL-18 -607C/A or -137G/C polymorphism and the risk of allergic disease (all P > 0.05). However, in a stratified analysis by type of allergic disease, our results indicated that IL-18 -607C/A polymorphism was associated with a significantly decreased risk of allergic asthma in heterozygous comparison and IL-18 -137G/C was associated with a significantly decreased risk of allergic dermatitis in recessive model and homozygous comparison. In the stratified analysis by source of control, IL-18-607C/A showed significantly reduced risk in population-based subgroup, and for IL-18 -137G/C only significantly decreased risk was found in the hospital-based subgroup. Our meta-analysis suggests that IL-18 -607C/A and -137G/C polymorphisms may be protective factors for the risk of allergic asthma and allergic dermatitis, respectively.

Estrogen receptor α gene polymorphisms and risk of Alzheimer's disease: evidence from a meta-analysis.

OBJECTIVE: Human estrogen receptor α (ESR1), a member of the nuclear receptor superfamily of ligand-activated transcription factors, is one of the key mediators of hormonal response in estrogen-sensitive tissues. Accumulating evidence has demonstrated that two of the most widely studied single-nucleotide polymorphisms in ESR1 - PvuII (T/C, rs223493) and Xbal (A/G, rs9340799) - are possibly associated with Alzheimer's disease (AD). However, individual study results are still controversial. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National Knowledge Infrastructure databases for eligible studies assessing the association of ESR1 polymorphisms and AD risk (last search performed in November 2013). Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was conducted to evaluate the association between ESR1 polymorphisms and susceptibility to AD. RESULTS: The results indicated that a significant association was found between the ESR1 PvuII polymorphism and AD risk in Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02-1.28, P=0.03; CT versus TT, OR 1.16, 95% CI 1.02-1.31, P=0.02), whereas no evidence of association was found in Asian populations. Nevertheless, we did not find any significant association between the ESR1 XbaI polymorphism and AD risk for any model in Caucasian and Asian populations (all P>0.05). CONCLUSION: Based on this meta-analysis, we conclude that the ESR1 PvuII polymorphism might be a risk factor in AD development in Caucasian populations, not in Asian populations. Further confirmation is needed from better-designed and larger studies.

E-selectin S128R polymorphism is associated with cancer risk: a meta-analysis.

BACKGROUND: Genetic factors have been shown to play an important role in the development of cancers. However, individual studies may fail to completely demonstrate complicated genetic relationships because of small sample size. Therefore, we performed a meta-analysis to evaluate the association of E-selectin Ser128Arg (S128R) with cancer risk. MATERIALS AND METHODS: A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure databases was carried out to identify studies of the association between E-selectin S128R polymorphism and cancer risk. The odds ratio (OR) with 95% confidence intervals (95%CIs) were used to assess the strength of association. RESULTS: A total of eight studies involving 1,675 cancer cases and 2,285 controls were included in the meta-analysis. In overall populations, S128R polymorphism seemed to be associated with cancer risk (Arg allele vs Ser allele: OR=1.65, 95%CI =1.33-2.04, p<0.01; Arg/Arg+Arg/Ser vs Ser/Ser: OR=1.87, 95%CI =1.48-2.36, p<0.01; Arg/Ser vs Ser/Ser: OR=1.80, 95%CI =1.51-2.14, p<0.01). Similarly, subgroup analysis by ethnicity and source of control also revealed that this polymorphism was related to cancer risk. CONCLUSIONS: Our meta-analysis revealed that there was association between the E-selectin S128R polymorphism and the risk of cancer. Further large and well-designed studies are needed to confirm this association.

Association between Toll-like receptor 3 polymorphisms and cancer risk: a meta-analysis.

Toll-like receptors (TLRs) are well known as molecular sensors of pathogen-associated molecular patterns. They control activation of the innate immune response and subsequently shape the adaptive immune response. Polymorphisms in TLR3 gene associated with cancer have been studied extensively. However, the results remain controversial. A literature search was performed among PubMed, Embase, Web of Science, Science Direct, Wanfang, and Chinese National Knowledge Infrastructure databases to identify eligible studies on the association between TLR3 polymorphisms and cancer risk. A total of 12 studies in 11 articles were included in the meta-analysis including 5,861 cases and 6,339 controls. Significant associations with cancer risk were observed for single nucleotide polymorphisms (SNPs) rs3775291 (allele model: odds ratio (OR) = 1.12, 95 % confidence interval (95 % CI) = 1.00-1.25, P = 0.04), rs3775290 (allele model: OR = 1.12, 95 % CI = 1.00-1.25, P = 0.04; dominant model: OR = 1.30, 95 % CI = 1.05-1.60, P = 0.01; homozygous comparison: OR = 1.68, 95 % CI = 1.06-2.68, P = 0.03; heterozygous comparison: OR = 1.25, 95 % CI = 1.01-1.55, P = 0.04), rs5743305 (allele model: OR = 1.07, 95 % CI = 1.01-1.15, P = 0.03; dominant model: OR = 1.11, 95 % CI = 1.01-1.22, P = 0.03), and rs5743312 (allele model: OR = 1.13, 95 % CI = 1.01-1.27, P = 0.03; recessive model: OR = 1.86, 95 % CI = 1.31-2.63, P < 0.01; homozygous comparison: OR = 1.88, 95 % CI = 1.33-2.67, P < 0.01), respectively. Meanwhile, we did not find any significant association with cancer risk for rs7657186 and rs7668666. In conclusion, this meta-analysis indicates a significant association of four TLR3 gene polymorphisms with cancer risk. However, because the study size was limited, further studies are essential to confirm our results.

[Role of antioxidant in protecting the biological function of hematopoietic stem cells].

In peripheral blood hematopoietic stem cell transplantation (PBHSCT) , the mobilization and circulating of bone marrow hematopoietic stem cells in blood with higher oxygen concentration all increase reactive oxygen species(ROS) production, which has negative effect on the biological function of BMHSC. In order to investigate the protective effect of antioxidant on hematopoietic stem cells (HSC), the ascorbic acid 2-phosphate (AA2P), an ascorbic acid derivative of vitamin C, was added in HSC culturing by imitating oxygen conditions which BMHSC experienced in peripheral blood stem cell transplantation. The protective effect of above-mentioned culture methods on the biologic functions of BMHSC was evaluated by vitro amplification assay, committed division assay, reactive oxygen species (ROS) measurement, CD34(+) HSC engraftment. The results showed that the ROS level in HSC from in vitro cultures was much higher than that freshly separated BMHSC, and the amplified AC133(+)CD34(+) HSC, BFU-E, CFU-GM, CFU-GEMM colonies, migration rate and severe combined immunodeficiency (SCID)-repopulating cells (SRC) were all much more than HSC cultured without AA2P. It is concluded that antioxidant intervention may be an effective methods for protecting the biological function of PBHSC and improving the therapeutic effect of PBHSCT.

Prognostic value of interleukin-8 and MMP-9 in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the leading causes of cancer related death in China. One of the reasons is the absence of tumor specific prognostic markers. The aim of this study was to examine the prognostic values of interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) in NPC patients. A total of 99 consecutive NPC patients and 40 healthy controls were recruited for this study. Serum levels of IL-8 and MMP-9 were evaluated in NPC patients who were followed up for 5 years. The serum levels of IL-8 and MMP-9 in NPC patients were significantly higher than those in healthy controls (IL-8 26.3 [2.9-68.0] ng/ml vs. 20.3 [2.3-38.6] ng/ml, P < 0.001; MMP-9 23.5 [3.6-52.1] ng/ml vs. 17.3 [2.6-36.9] ng/ml, P = 0.002), respectively. The serum levels of IL-8 and MMP-9 were positively correlated with the N classification (IL-8, P = 0.041, and MMP-9, P < 0.001, respectively) and clinical stage (IL-8, P = 0.022, and MMP-9, P < 0.001, respectively) in NPC patients. Analysis using the Kaplan-Meier method indicated that patients with high levels of IL-8 or MMP-9 had significantly shorter overall survival (OS) (IL-8, P = 0.012; MMP-9, P < 0.001) and disease-free survival (DFS) (IL-8, P = 0.021; MMP-9, P = 0.003) time than those with low levels of MMP-9 or IL-8. Univariate and multivariate analysis revealed elevated MMP-9 level was an independent predictor of shorter OS and DFS. Both MMP-9 and IL-8 are involved in NPC progression. MMP-9 in serum may be the clinically useful indicator for prognostic evaluation in NPC patients.

Vascular endothelial growth factor +936C/T, -634G/C, -2578C/A, and -1154G/A polymorphisms with risk of preeclampsia: a meta-analysis.

BACKGROUND: Emerging evidence showed that VEGF gene polymorphisms are involved in the regulation of VEGF protein expression, thus increasing an individual's susceptibility to preeclampsia (PE); but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between VEGF gene polymorphisms and PE risk. METHODS: A systematic literature search of MEDLINE, Embase, Web of Science, and CNKI (Chinese National Knowledge Infrastructure) databases was conducted. Statistical analyses were performed using STATA 12.0 software and Review manager 5.1. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. RESULTS: According to the inclusion criteria, 11 case-control studies were finally included in this meta-analysis. A total of 1,069 PE cases and 1,315 controls were included in this study. Our meta-analysis indicated that VEGF +936C/T (T vs. C, OR = 1.52, 95%CI = 1.08-2.12) or -634G/C polymorphism (C vs. G, OR = 1.24, 95% CI = 1.03-1.50) was associated with the risk of PE, whereas there was no association between -2578C/A (A vs. C, OR = 0.98, 95%CI = 0.82-1.16) or -1154G/A (A vs. G, OR = 1.30, 95%CI = 0.94-1.78) polymorphism and PE risk in our study. CONCLUSION: Our meta-analysis suggested that VEGF -2578C/A or -1154G/A polymorphism had no association with PE risk in all examined patients, whereas there was an association between VEGF +936C/T or -634G/C polymorphism and risk of PE.

[Influence of reactive oxygen species on mouse bone marrow hematopoietic stem cell apoptosis].

Objective of this study was to investigate the mechanism of the biological function damage resulting from increased ROS in peripheral blood stem cells during peripheral blood stem cell transplantation. Bone marrow hematopoietic stem cells (BMHSC) were cultured at the oxygen concentration imitated according to the bone marrow oxygen concentration (5% O2) including mean venous oxygen concentration (12% O2), mean arterial oxygen concentration (20% O2). The ROS level in BMHSC was detected by using fluorescent probe, the percentage of BM-HSC in cell cycle was determined by flow cytometry, the apoptosis rate was assayed by Annexin V/PI double staining, the expression levels of ATM gene and P21 protein were measured by PCR and Western respectively. The results showed that as compared with control group (5% O2), the ROS levels were lower, the percentage of cells in G1, S,G2/M phase increased (P < 0.01), the apoptosis rate of cells obviously increased (P < 0.01), the expression level of ATM gene obviously decreased (P < 0.01), while the expression level of P21 protein significantly was enhanced (P < 0.01) in 12% O2, 20% O2 and 5%-12%-20% O2 groups. It is concluded that ROS results in the apoptosis of BMHSC through inhibiting the expression of ATM gene and activating P21 protein.

Positive association between Interleukin-8 -251A > T polymorphism and susceptibility to gastric carcinogenesis: a meta-analysis.

BACKGROUNDS: The associations between the polymorphisms of interleukin-8 (IL-8) gene and gastric carcinogenesis have been extensively investigated in recent years. However, the results remain conflicting rather than conclusive. METHODS: A meta-analysis of 18 eligible studies was performed to evaluate the association of IL-8 -251A > T polymorphism with risk of gastric carcinogenesis. A systematic literature search of MEDLINE, Embase, and Web of Science, CNKI databases was conducted. Statistical analysis was performed by using the Revman 5.1 software and the Stata 12.0 software. RESULTS: Of the 293 unique studies identified using our search criteria, 18 studies fulfilled our inclusion criteria and were included in the meta-analysis. These studies cumulatively reported 5,321 cases and 6,465 controls. The combined results based on all studies showed that the IL-8 -251A > T polymorphism was associated with the risk of gastric carciongenesis (A vs. T OR: 1.14 [1.02, 1.26], P = 0.02), especially gastric cancer (A vs. T OR: 1.15 [1.03, 1.29], P = 0.02), but not associated with the risk of precancerous lesion (A vs. T OR: 1.09 [0.99, 1.20], P = 0.08). Analysis stratified by ethnicity may seem that IL-8 -251A > T polymorphism was susceptible to gastric cancer in Asian population, but not in Caucasian population. CONCLUSIONS: Our meta-analysis results provide evidence that IL-8 -251A > T polymorphism is significantly associated with increased risk of gastric carcinogenesis in Asian population, particularly in gastric cancer. Further large and well-designed studies are required to confirm this conclusion.

High TMPRSS4 expression is a predictor of poor prognosis in cervical squamous cell carcinoma.

OBJECTIVE: The aim of this study was to clarify the clinical role of TMPRSS4 expression in cervical squamous cell carcinoma (CSCC) and to investigate the role of TMPRSS4 in predicting outcomes of patients with CSCC. METHODS: The retrospective study enrolled 87 patients diagnosed with CSCC between 2004 and 2006. TMPRSS4 expression in CSCC was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. The impact of TMPRSS4 expression on 5-year disease-free survival (DFS) and 5-year overall survival (OS) was assessed by Kaplan-Meier analysis and Cox proportional hazards modeling. RESULTS: The high expression of TMPRSS4 was 63.2% in 87 patients with CSCC, and 17.5% in 40 patients with benign cervical disease (P<0.001). High TMPRSS4 expression was significantly associated with tumor grade (P=0.005), lymph node metastasis (P=0.004), and deep cervical stromal invasion (P=0.025). Patients with high expression of TMPRSS4 had shorter OS and DFS than those with low expression (P=0.0205 and P=0.0318, respectively). In multivariate Cox regression analysis, high expression of TMPRSS4 was a potential prognostic indicator for OS (P=0.041) and DFS (P=0.015). CONCLUSION: Our findings suggest that TMPRSS4 might play an important role in the progression of CSCC. TMPRSS4 could be a potential prognostic marker of CSCC.

TMPRSS4 as a poor prognostic factor for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by the lack of immunohistochemical staining for estrogen receptors (ER), progesterone receptors (PR), and lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). Our aim was to investigate the expression of transmembrane protease, serine 4 (TMPRSS4) in TNBC patients and its possible relationship to the outcome of the disease. A total of 72 TNBC patients and 109 non-TNBC patients who were diagnosed between 2003 and 2008 were enrolled in this study. Immunohistochemistry was used to compare the expression pattern of TMPRSS4 in TNBC and non-TNBC groups, and the prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression in TNBC patients. The rate of high expression of TMPRSS4 was significantly higher in TNBC group than that in non-TNBC group. High expression of TMPRSS4 was significantly correlated with lymph node metastasis, histological grade, and tumor size. TNBC patients with high TMPRSS4 expression showed the poorer overall survival (OS) and disease-free survival (DFS) than those patients with low TMPRSS4 expression. In multivariate analysis, only lymph node metastasis and TMPRSS4 expression were the independent prognostic factors for OS and DFS in TNBC. Our study provides evidence that TMPRSS4 expression is associated with lymph node metastasis, tumor size, and histological grade in TNBC patients, and also is an independent prognostic factor for TNBC.