In vitro promotion of SDF-1α on the migration and proliferation of C-kit+ cardiac stem cells in neonatal mice.

The aim of this study was to explore the In Vitro effects of stromal-derived factor-1α (SDF-1α) on the migration and proliferation of c-kit+ cardiac stem cells. The lentivirus containing SDF-1α (LV-SDF-1α) was constructed. Primary myocardial fibroblasts were transfected by LV-SDF-1α, followed by primary culture of cardiac tissue cells and separation of c-kit+ cardiac stem cells with a flow cytometer, in order to investigate the effects of SDF-1α on the migration and proliferation of c-kit+ cardiac stem cells using cell co-culture, immunofluorescence and EdU tracing technologies. The results showed that myocardial fibroblasts could secrete SDF-1α after the transfection with LV-SDF-1α. High-purity c-kit+ cardiac stem cells were obtained through flow cytometry sorting and the positive rate was about 40%. The c-kit+ cardiac stem cells cultured In Vitro could be differentiated into cTnT positive cardiomyocyte-like cells. After co-culture of myocardial fibroblasts and c-kit+ cardiac stem cells transfected with lentivirus, SDF-1α might increase the migration of c-kit+ cardiac stem cells, but SDF-1α did not promote the proliferation of c-kit+ cardiac stem cells. In conclusion, the myocardial fibroblasts transfected with lentivirus can highly express SDF-1α, c-kit+ cardiac stem cells can be differentiated into cTnT positive cardiomyocyte-like cells and SDF-1α can effectively enhance the migration of c-kit+ cardiac stem cells but fails to stimulate the proliferation.

CHO cathepsin B identified as the protease responsible for a target bispecific antibody fragmentation.

In a previous work we demonstrated that CHO protease caused fragmentation of an expressed bispecific antibody (bsAb) and this detrimental host cell protein (HCP) can be effectively removed through an optimized Protein A wash step. In addition, preliminary evidence suggested that the responsible protease belongs to the threonine or cysteine protease family. In the current study, this protease was further identified as cathepsin B. First, we identified several CHO proteases in the further fractionated Protein A wash using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this allowed us to select four candidate proteases. Next, by examining the cleavage pattern of each individual protease and comparing it with that observed during purification, cathepsin B was identified as the protease responsible for the observed bsAb fragmentation.

Prognostic and clinicopathological significance of miR-638 in cancer patients: A meta-analysis.

INTRODUCTION: MiR-638 is believed to be involved in human cancers. However, the prognostic value of miR-638 in human carcinomas is controversial and inconclusive. Therefore, we conducted this meta-analysis to investigate the association between miR-638 expression and clinical outcomes in the patients with various cancers. METHODS: We searched Pubmed, Embase, Wanfang, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2020 to identify relevant studies. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to correlate expression of miR-638 with prognosis and clinicopathological features. RESULTS: A total of 18 studies involving 1886 patients were included in the meta-analysis. The results revealed that low miR-638 expression was significantly correlated with poor overall survival (OS) (HR = 2.09, 95% CI: 1.46-2.98, P < .001), but not with disease-free survival (DFS) (HR = 1.71, 95% CI: 0.31-9.56, P = .540). Subgroup analysis found that low miR-638 expression was associated with worse OS in patients with digestive system cancer (HR = 2.47, 95% CI: 1.85-3.30, P < .001), the reported directly from articles group (HR = 2.12, 95% CI: 1.34-3.33, P < .001), survival curves group (HR = 2.02, 95% CI: 1.07-3.80, P = .029), in studies with sample size ≥100 (HR = 2.12, 95% CI: 1.34-3.35, P = .001), and in studies with sample size <100 (HR = 2.02, 95%CI: 1.09-3.75, P = .025). Moreover, cancer patients with low miR-638 expression were prone to tumor size (OR = 1.47, 95% CI: 1.03-2.09, P = .035), earlier lymph node metastasis (present vs absent, OR = 2.26, 95% CI: 1.63-3.14, P < .001), earlier distant metastasis (present vs absent, OR = 2.60, 95% CI: 1.45-4.67, P < .001), TNM stage (III-IV vs I-II, OR = 2.01, 95% CI: 1.35-2.99, P = .001), and portal vein invasion (present vs absent, OR = 4.39, 95% CI:2.23-8.64, P < .001), but not associated with age, gender, tumor differentiation, and vascular invasion. CONCLUSIONS: MiR-638 may serve as a promising indicator in the prediction of prognosis and clinicopathological features in patients with different kinds of cancers.

Prognostic and clinicopathological significance of MicroRNA-153 in human cancers: A meta-analysis.

BACKGROUND: Several studies have explored the prognostic value of MicroRNA-153 (miR-153) in various cancers, but obtained inconsistent results. Thus, we conducted a meta-analysis to assess the prognostic significance of miR-153 for patients with cancer. METHODS: Eligible studies were identified by searching the online databases Pubmed, Embase, Web of Science, Medline,and the China National Knowledge Infrastructure (CNKI) up to March 2020. Hazard ratios (HRs) with 95% CIs and were calculated to clarify the correlation between miR-153 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between miR-153 with clinicopathological characteristics of cancer patients. RESULTS: In total, 933 patients from 11 articles were enrolled in our meta-analysis. The results revealed that low miR-153 expression was significantly correlated with poor overall survival (OS) (HR = 2.45, 95% CI = 1.66-3.63, P < .001), but not with disease-free survival (DFS) (HR = 1.67, 95% CI = 0.45-6.19, P = .442). Subgroup analysis found that low miR-153 expression was associated with worse OS in the reported directly from articles group (HR = 2.67, 95% CI: 1.32-5.37, P = .006), survival curves group (HR = 2.10, 95% CI: 1.56-2.84, P < .001), digestive system tumor (HR = 2.76, 95% CI: 1.73-4.41, P < .001), and breast cancer (HR = 4.01, 95% CI: 1.46-11.04, P = .007).Moreover, cancer patients with low miR-153 expression were prone to poor tumor differentiation(poor vs well+moderate, OR = 2.41, 95% CI = 1.52-3.82, P < .001), earlier lymph node metastasis (present vs absent, OR = 2.19, 95% CI = 1.12-4.25, P = .021) and earlier distant metastasis (present vs absent,OR = 8.24, 95% CI = 2.93-23.21, P < .001), but not associated with age,gender and TNM stage. CONCLUSIONS: This meta-analysis indicated that low miR-153 expression is associated with poor prognosis. miR-153 may serve as an effective predictive biomarker for tumor prognosis, especially for digestive system tumor and breast cancer.

Nrf2 activation mediates tumor-specific hepatic stellate cells-induced DIgR2 expression in dendritic cells.

Our previous studies discovered that tumor-specific hepatic stellate cells (tHSCs) induced dendritic cell-derived immunoglobulin receptor 2 (DIgR2) expression in bone marrow-derived dendritic cells (mDCs), inhibiting splenic T cell activation. The current study aims to explore the underlying mechanism of DIgR2 expression by focusing on Nrf2 (nuclear-factor-E2-related factor 2) signaling. We show that tHSCs co-culture induced significant Nrf2 signaling activation in mDCs. The latter was evidenced by Nrf2-Keap1 disassociation, Nrf2 protein stabilization, accumulation and nuclear translocation. Expression of Nrf2-dependent genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), were detected in tHSCs-co-cultured mDCs. Importantly tHSCs-induced DIgR2 expression was blocked by Nrf2 shRNA or knockout (KO, by CRISPR/Cas9 method). Conversely, forced activation of Nrf2, by Keap1 shRNA or the Nrf2 activators (3H-1,2-dithiole-3-thione and MIND4-17), induced significant DIgR2 expression. tHSCs stimulation induced reactive oxygen species (ROS) production in mDCs. Conversely, ROS scavengers inhibited tHSCs-induced ROS production, Nrf2 activation and DIgR2 expression in mDCs. Significantly, tHSCs inhibited production of multiple cytokines (CD80, CD86 and IL-12) in mDCs, reversed by Nrf2 depletion. Moreover, Nrf2 shRNA or KO attenuated splenic T cell inhibition by tHSCs-stimulated mDCs. Together, we conclude that Nrf2 activation mediates tHSCs-induced DIgR2 expression in mDCs.

Prognostic value of high stanniocalcin 2 expression in solid cancers: A meta-analysis.

BACKGROUND: Several studies have explored the prognostic value of stanniocalcin 2 (STC2) in various cancers, but obtained inconsistent results. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathologic significance of STC2 in various cancers. METHODS: Eligible studies were identified by searching the online databases PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure up to March 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) and were calculated to clarify the correlation between STC2 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between STC2 with clinicopathologic characteristics of patients with cancer. RESULTS: A total of 16 eligible studies with 4074 patients with cancer were included in our meta-analysis. The results showed that high STC2 expression can predict poor overall survival (OS) for cancer (HR = 1.48, 95% CI: 1.15-1.90, P = .002). Subgroup analysis found that high STC2 expression was associated with worse OS in Asian (HR = 1.85, 95% CI: 1.35-2.55), the reported directly from articles group (HR = 1.39, 95% CI: 1.05-1.84), survival curves group (HR = 1.93, 95% CI: 1.36-2.74), and gastric cancer (HR = 1.43, 95% CI: 1.04-1.95). Furthermore, high STC2 expression was significantly related to advanced T stage (OR = 1.83, 95% CI: 1.17-2.86, P = .008), lymph node metastasis (OR = 2.29, 95% CI: 1.51-3.45, P < .001), lymphatic invasion (OR = 2.15, 95% CI: 1.53-3.02, P < .001), venous invasion (OR = 1.97, 95% CI: 1.30-2.99, P = .001), and more advanced clinical stage (OR = 2.36, 95% CI: 1.74-3.19, P < .001) CONCLUSION:: Elevated expression of STC2 suggested a poor prognosis in patients with cancer and may serve as a new tumor marker to monitor cancer development and progression.

Prognostic and clinicopathological significance of S100A14 expression in cancer patients: A meta-analysis.

BACKGROUND: The prognostic significance of S100A14 for survival of cancer patients remains controversial. Therefore, we conducted this meta-analysis to explore the association between S100A14 expression and cancer prognosis. METHOD: Eligible studies were identified by searching the online databases Pubmed and EMBASE up to August 2018. Odds ratios (ORs) with 95% confidence intervals (CIs) severed as the summarized statistics for clinicopathological assessments and hazard ratios (HRs) with 95% CIs were calculated to clarify the correlation between S100A14 expression and prognosis of different cancers. RESULTS: A total of 11 studies with 1651 cancer patients were enrolled. The results indicated that S100A14 expression was not significantly associated with overall survival (OS) in total various cancers (HR = 1.54, 95% CI:0.89-2.67, P = .121). Further subgroup analysis stratified by tumor type showed that elevated S100A14 expression was associated with poor OS in breast cancer (HR = 3.66, 95% CI: 1.75-7.62, P < .001) and in ovarian cancer patients (HR = 3.78, 95%CI: 1.63-8.73, P = .002). Interestingly, high S100A14 expression was correlated with poor tumor differentiation (OR = 2.51, 95% CI: 1.52-4.13, P < .001). However, there were no significant correlations between S100A14 expression and other clinicopathologic characteristics. Begg funnel plot and Egger test showed that no publication bias was detected. CONCLUSIONS: Our meta-analysis suggests that S100A14 overexpression might be a predictive biomarker for poor prognosis in patients with breast cancer and ovarian cancer. Large-scale studies are required to confirm these results.

Association between IL-17A G197A polymorphism and gastric cancer risk: an updated meta-analysis based on 6,624 cases and 7,631 controls.

PURPOSE: Previous studies investigating the association between interleukin-17A (IL-17A) G197A polymorphism and gastric cancer risk have provided inconsistent results. We, therefore, conducted this meta-analysis to clarify the association between IL-17A G197A polymorphism and gastric cancer risk. METHODS: We searched PubMed, Excerpta Medica Database, and CNKI databases to identify relevant studies up to June 10, 2017. A total of 16 case-control studies including 6,624 cases and 7,631 controls were identified. RESULTS: Overall, significant associations between IL-17A G197A polymorphism and gastric cancer risk were observed (A vs G: OR =1.24, 95% CI =1.14-1.36; AA vs GG: OR =1.63, 95% CI =1.35-1.96; GA vs GG: OR =1.12, 95% CI =1.01-1.25; AA+GA vs GG: OR =1.23, 95% CI =1.11-1.35; AA vs GA+GG: OR =1.54, 95% CI =1.27-1.87). Similar associations were also observed in Asian population (A vs G: OR =1.25, 95% CI =1.15-1.37; AA vs GG: OR =1.62, 95% CI =1.33-1.97; GA vs GG: OR =1.16, 95% CI =1.07-1.25; AA+GA vs GG: OR =1.24, 95% CI =1.15-1.33; AA vs GA+GG: OR =1.51, 95% CI =1.23-1.85), in Caucasian population (AA vs GA+GG: OR =2.19, 95% CI =1.40-3.44), and in the hospital-based controls' subgroup (A vs G: OR =1.30, 95% CI =1.17-1.45; AA vs GG: OR =1.81, 95% CI =1.46-2.25; AA+GA vs GG: OR =1.27, 95% CI =1.12-1.43; AA vs GA+GG: OR =1.71, 95% CI =1.34-2.18). CONCLUSIONS: The current meta-analysis suggests that IL-17A G197A polymorphism might enhance gastric cancer risk.

DlgR2 knockdown boosts dendritic cell activity and inhibits hepatocellular carcinoma tumor in-situ growth.

Tumor-specific hepatic stellate cells (tHSCs) positively participate in human hepatocellular carcinoma (HCC) tumorigenesis and progression. Our previous studies have shown that tHSCs co-culture with dendritic cells (DCs) induced DIgR2 (dendritic cell-derived immunoglobulin receptor 2) expression. The latter is a member of IgSF inhibitory receptor suppressing DCs-initiated antigen-specific T-cell responses. In the current study, we show that hepatic artery injection of DlgR2 siRNA significantly inhibited in-situ HCC xenograft growth in rat livers. Further, 5-FU-medied inhibition of in-situ HCC growth was dramatically sensitized with DlgR2 silence. DlgR2 siRNA injection indeed downregulated DlgR2 in ex-vivo cultured tumor-derived DCs (tDCs). More importantly, tDCs activity was boosted following DlgR2 siRNA. These cells presented with upregulated CD80, CD86 and MHC-II. Production of interleukin-12 and tumor necrosis factor-α was also increased in the DlgR2-silenced tDCs. We propose that DlgR2 knockdown likely boosts the activity of tumor-associated DCs, and inhibits growth of in-situ HCC xenografts.

Tumor-specific hepatic stellate cells (tHSCs) induces DIgR2 expression in dendritic cells to inhibit T cells.

Tumor-specific hepatic stellate cells (tHSCs) contributes to tumorigenesis and progression of hepatocellular carcinoma (HCC). The potential function of tHSCs on dendritic cells (DCs) was studied here. We discovered that tHSCs co-culture induced upregulation of DIgR2 (dendritic cell-derived immunoglobulin receptor 2) in bone marrow-derived DCs (mDCs). Activation of MEK-ERK is required for DIgR2 expression in mDCs. MEK-ERK inhibitors or shRNA-mediated silence of MEK1/2 in mDCs inhibited tHSCs-induced DIgR2 expression. Meanwhile, tHSCs stimulation decreased production of multiple cytokines (CD80, CD86 and IL-12) in mDCs. Such an effect was almost reversed by DIgR2 shRNA in mDCs. Further, tHSCs-stimulated mDCs induced T-cell hypo-responsiveness, leading to decreased cytotoxic T lymphocyte (CTL) activity and reduced IFN-γ production in splenic T cells. T cell proliferation inhibition and apoptosis were also noticed. These actions on T cells were again largely inhibited by DIgR2 shRNA in mDCs. Together, our results indicate that tHSCs directly induces DIgR2 expression in DCs to inhibit T cells.

Hypolipidemic effects of flavonoids extracted from Lomatogonium rotatum.

Contained in the Mongolian volumes of Chinese Materia Medica, Lomatogonium rotatum Fries ex Nym. may reduce blood lipid levels and prevent obesity; however, its exact mechanism of action remains unclear. The present study investigated the hypolipidemic and obesity-inhibiting effects of four similarly structured flavonoids extracted from L. rotatum. According to a well-established method, flavonoids such as decussatin were extracted from the whole herb of L. rotatum, and male Wistar rats were subsequently fed a high-fructose diet supplemented with flavonoids (20 mg/kg) for 12 weeks. The levels of total cholesterol, triglyceride (TG), low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol (HDL-C) were detected. In addition, hepatic and epididymal adipose tissues were weighed, and levels of blood glucose, alanine aminotransferase, aspartate aminotransferase, non-esterified fatty acid, insulin and leptin were determined. The mRNA expression levels of fatty acid synthase (FAS) were analyzed using a reverse transcription polymerase chain reaction; whereas FAS, adenosine monophosphate-activated protein kinase (AMPK) and threonine-172 phosphorylated AMPK protein levels were detected by western blotting. The epididymal adipose tissues of rats fed with flavonoids were lighter, as compared with those fed with fructose in the model group. Following a 12-week administration of flavonoids, the serum levels of fasting blood glucose, feeding blood glucose and leptin were decreased. Furthermore, flavonoid treatment reduced TG and cholesterol levels in the blood and increased serum HDL-C levels, as compared with the model group. High-fructose diet administration significantly increased FAS mRNA and protein expression levels, whereas the FAS protein levels of flavonoid-treated rats were markedly reduced. The flavonoid compounds also enhanced threonine-172 phosphorylation of AMPK in the liver lysate, and all flavonoids successfully downregulated leptin levels and the majority decreased the relative weights of epididymal adipose tissue. Therefore, flavonoids may function in a similar way to epigallocatechin gallate, which has previously been shown to inhibit FAS activity by stimulating AMPK in hepatocyte cells via the liver kinase B1 pathway.

Prognostic role of LSD1 in various cancers: evidence from a meta-analysis.

The prognostic value of lysine-specific demethylase 1 (LSD1) overexpression in various cancers has been investigated by many studies with inconsistent results. A meta-analysis was performed to assess the association between LSD1 and overall survival (OS) in cancer patients. Eligible studies were identified by searching the online databases PubMed and China National Knowledge Infrastructure up to February 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between LSD1 expression and prognosis of different cancers. In total, nine studies with 1,149 cancer patients were included for final analysis. The meta-analysis suggested that LSD1 overexpression was associated with poor OS in cancer patients (HR =1.80, 95% CI: 1.39-2.34, P=0.000). Subgroup analysis by ethnicity, cancer type and HR estimate also showed that high levels of LSD1 were significantly correlated with OS. The meta-analysis showed that LSD1 overexpression may be associated with a worse prognosis in cancer patients.

Association between RAD51 polymorphisms and susceptibility of head and neck cancer: a meta-analysis.

BACKGROUND: The associations between RAD51 gene polymorphisms (G135C and G172T) and risk of head and neck cancer (HNC) have been investigated, but the results are controversial. The aim of this study was to provide a more precise estimation of its relationship with HNC using a meta-analysis. METHODS: Relevant studies were retrieved from the PubMed, Excerpta Medica Database, and China National Knowledge Infrastructure. Strict selection and exclusion criteria were determined, and the odds ratio (OR) with a 95% confidence interval (CI) was used to assess the strength of the association between RAD51 polymorphisms and HNC risk. RESULTS: Six studies were eligible for RAD51 G135C (1593 cases and 1719 controls), and three studies were eligible for RAD51 G172T (997 cases and 979 controls). In the overall population, significant association between RAD51 G135C polymorphism and HNC risk was observed under allele model (C vs G: OR = 1.21, 95% CI = 1.04-1.41, P = 0.015). In the subgroup analysis by smoking status, a significant association was found among smokers (C vs G: OR = 1.59, 95% CI = 1.25-2.04; GC vs GG: OR = 2.29, 95% CI = 1.29-4.05; GC + CC vs GG: OR = 2.08, 95% CI = 1.56-2.78). When stratified based on drinking status, a significant association was found among drinkers(C vs G: OR = 1.60, 95% CI = 1.21-2.11; GC vs GG: OR = 2.50, 95% CI = 1.16-5.38; GC + CC vs GG: OR = 2.17,95% CI = 1.56-3.01). However, no significant association with HNC risk was demonstrated when stratified based on source of control and ethnicity. For G172T polymorphism, the results showed no significant risk association in overall analysis. In the subgroup analysis by ethnicity, the result suggested that a decreased HNC risk was found among Caucasians (T vs G: OR = 0.82, 95% CI = 0.72-0.95; TT vs GG: OR = 0.62, 95% CI = 0.46-0.84; TT vs GT + GG: OR = 0.64, 95% CI = 0.49-0.84). CONCLUSION: This meta-analysis suggested that RAD51 G135C is associated with increased HNC risk, especially among smokers and drinkers, while G172T polymorphism may play a protective role against HNC among Caucasians. Larger-scale and well-designed studies are needed to further clarify the association.

Alterations in the endometrium of rats, rabbits, and Macaca mulatta that received an implantation of copper/low-density polyethylene nanocomposite.

A copper/low-density polyethylene nanocomposite (nano-Cu/LDPE), a potential intrauterine device component material, has been developed from our research. A logical extension of our previous work, this study was conducted to investigate the expression of plasminogen activator inhibitor 1 (PAI-1), substance P (SP), and substance P receptor (SP-R) in the endometrium of Sprague Dawley rats, New Zealand White rabbits, and Macaca mulatta implanted with nano-Cu/LDPE composite. The influence of the nano-Cu/LDPE composite on the morphology of the endometrium was also investigated. Animals were randomly divided into five groups: the sham-operated control group (SO group), bulk copper group (Cu group), LDPE group, and nano-Cu/LDPE groups I and II. An expression of PAI-1, SP, and SP-R in the endometrial tissues was examined by immunohistochemistry at day 30, 60, 90, and 180 postimplantation. The significant difference for PAI-1, SP, and SP-R between the nano-Cu/LDPE groups and the SO group (P<0.05) was identified when the observation period was terminated, and the changes of nano-Cu/LDPE on these parameters were less remarkable than those of the Cu group (P<0.05). The damage to the endometrial morphology caused by the nano-Cu/LDPE composite was much less than that caused by bulk copper. The nano-Cu/LDPE composite might be a potential substitute for conventional materials for intrauterine devices in the future because of its decreased adverse effects on the endometrial microenvironment.

Lack of association between vitamin D receptor gene BsmI polymorphism and breast cancer risk: an updated meta-analysis involving 23,020 subjects.

The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. A great number of studies regarding the association between BsmI polymorphism in the VDR gene and breast cancer have been published. However, the results have been contradicting. Therefore, we conducted a meta-analysis to re-examine the controversy. Published literatures from PubMed, Embase, and Chinese Biomedical Literature Database (CBM) were searched (updated to July 10, 2013). The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for breast cancer risk associated with VDR BsmI polymorphism. With all studies involved, the meta-analysis results suggest no statistically significant association between VDR BsmI polymorphism and breast cancer risk (B vs. b, OR = 0.922, 95% CI = 0.836-1.018, P = 0.108, I (2) = 80.0%; BB vs. bb, OR = 0.843, 95% CI = 0.697-1.021, P = 1.75, I (2) = 75.5%; Bb vs. bb, OR = 0.930, 95% CI = 0.814-1.063, P = 0.31, I (2) = 73.1%; BB+Bb vs. bb, OR = 0.906, 95% CI = 0.787-1.043, P = 1.37, I (2) = 78.7%; BB vs. bb+Bb, OR = 0.899, 95% CI = 0.786-1.028, P = 1.56, I (2) = 61.0%). The results were not changed when studies were stratified by ethnicity or source of controls. This meta-analysis suggested that there were no associations between VDR BsmI polymorphism and breast cancer.

Lack of association between the FAS/FASL polymorphisms and cervical cancer risk: A meta-analysis.

FAS/FASL gene promoter polymorphisms are associated with cervical cancer risk, however, results from previous studies have been conflicting. To obtain a more precise estimation of the association between these polymorphisms and cancer risk, a meta-analysis was performed. All eligible studies up to November 1st, 2012, concerning FAS-670 A/G, FAS-1377 G/A and FASL-844 T/C polymorphisms and cervical cancer risk, were collected from the following electronic databases: PubMed, Excerpta Medica Database and Chinese Biomedical Literature Database. The odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of the association via the additive, codominant, dominant and recessive models. In total, 10 publications with 11 case-control studies (10 on FAS-670 A/G, 5 on FAS-1377 G/A and 6 on FASL-844 T/C polymorphisms) were included in this meta-analysis. No association between FAS-670 A/G, FAS-1377 G/A and FASL-844 T/C polymorphisms and cervical cancer susceptibility for all the genetic models was identified. Following stratification of the studies by ethnicity or source of controls, similar results were obtained. In conclusion, our findings showed that the FAS-670 A/G, FAS-1377 G/A and FASL-844 T/C polymorphisms are not associated with cervical cancer risk. Future studies with larger sample sizes are required to further evaluate these associations.

Lack of association between interleukin-8-251 T>A polymorphism and colorectal cancer risk: a meta-analysis based on 3,019 cases and 3,984 controls.

PURPOSE: The results of recent published studies focusing on IL-8 polymorphism in colorectal cancer susceptibility have often been inconsistent. We therefore carried out a meta-analysis based on independent studies to assess the association. METHODS: Nine case-control studies with 7,003 individuals (3,019 cases and 3,984 controls) were included in this meta-analysis through searching the databases of PubMed, Excerpta Medica Database (EMBASE), and Chinese Biomedical Literature Database (CBM; Chinese) (up to Aug 1st, 2012). The odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of the association. Meta-analysis was conducted in a fixed/random effect model. RESULTS: No obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (for A vs. T: OR = 1.084, 95% CI = 0.971- 1.209, P = 0.019; for TA vs. TT: OR = 1.18, 95% CI = 0.943-1.475, P = 0.001; for AA vs. TT: OR = 1.155, 95% CI = 0.916-1.456, P = 0.014; for AA+TA vs. TT: OR = 1.170, 95% CI =0.953-1.437, P = 0.001; for AA vs. TT+TA: OR = 1.044, 95% CI = 0.886-1.230, P = 0.097). In the subgroup analyses by ethnicity (Caucasian) and source of controls (population based), also no significant associations were found for all genetic models. CONCLUSIONS: Result suggests that the IL-8-251T>A polymorphism is not associated with colorectal cancer risk. Because of the limitations of this meta-analysis, this finding demands further investigation.

Synergistic effects of exemestane and aspirin on MCF-7 human breast cancer cells.

OBJECTIVE: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. METHODS: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. RESULTS: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the G0/G1 phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. CONCLUSION: These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormone- dependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.