Characteristics of studies about radial scars and breast cancer included in the meta-analysis.

<p>Notes: NHS: Nurses’ Health Studies; NBC: Nashville Breast Cohort; Ca: Canada; Cases: patients with subsequent breast cancer; Controls: patients without subsequent breast cancer.</p

Flow chart of the selection of studies included in the meta-analysis.

<p>Flow chart of the selection of studies included in the meta-analysis.</p

Forest plots for the association between radial scars and breast cancer risk among women with PDWA.

<p>Forest plots for the association between radial scars and breast cancer risk among women with PDWA.</p

Subgroup analysis.

<p>Subgroup analysis.</p

Inflammatory Serum Proteins Are Severely Altered in Metastatic Gastric Adenocarcinoma Patients from the Chinese Population

<div><p>Background</p><p>Inflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups.</p><p>Methods</p><p>Serum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay.</p><p>Results</p><p>The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA.</p><p>Conclusions</p><p>These results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer.</p></div

MicroRNA-3646 Contributes to Docetaxel Resistance in Human Breast Cancer Cells by GSK-3β/β-Catenin Signaling Pathway

<div><p>Acquisition of resistance to docetaxel (Doc) is one of the most important problems in treatment of breast cancer patients, but the underlying mechanisms are still not fully understood. In present study, Doc-resistant MDA-MB-231 and MCF-7 breast cancer cell lines (MDA-MB-231/Doc and MCF-7/Doc) were successfully established <i>in vitro</i> by gradually increasing Doc concentration on the basis of parental MDA-MB-231 and MCF-7 cell lines (MDA-MB-231/S and MCF-7/S). The potential miRNAs relevant to the Doc resistance were screened by miRNA microarray. We selected 5 upregulated miRNAs (has-miR-3646, has-miR-3658, has-miR-4438, has-miR-1246, and has-miR-574-3p) from the results of microarray for RT-qPCR validation. The results showed that expression level of miR-3646 in MDA-MB-231/Doc cells was significantly higher than in MDA-MB-231/S cells. Compared to MCF-7/S cells, miR-3646 expression was up-regulated in MCF-7/Doc cells. Further studies revealed that transfection of miR-3646 mimics into MDA-MB-231/S or MCF-7/S cells remarkably increased their drug resistance, in contrast, transfection of miR-3646 inhibitors into MDA-MB-231/Doc or MCF-7/Doc cells resulted in significant reduction of the drug resistance. By the pathway enrichment analyses for miR-3646, we found that GSK-3β/β-catenin signaling pathway was a significant pathway, in which GSK-3β was an essential member. RT-qPCR and Western blot results demonstrated that miR-3646 could regulate GSK-3β mRNA and protein expressions. Furthermore, a marked increase of both nuclear and cytoplasmic β-catenin expressions (with phosphorylated-β-catenin decrease) was observed in MDA-MB-231/Doc cells compared with MDA-MB-231/S cells, and their expression were positively related to miR-3646 and negatively correlated with GSK-3β. Taken together, our results suggest that miR-3646-mediated Doc resistance of breast cancer cells maybe, at least in part, through suppressing expression of GSK-3β and resultantly activating GSK-3β/β-catenin signaling pathway.</p></div

RT-qPCR and Western blot analysis of β-catenin and P-β-catenin expression in MDA-MB-231/S and MDA-MB-231/Doc cells.

<p><b>a</b> Protein expression of β-catenin and P-β-catenin in MDA-MB-231/S and MDA-MB-231/Doc cells. <b>b</b> Protein expression of β-catenin and P-β-catenin in MDA-MB-231/S cells transfected with miR-3646 mimics, NC and blank control. <b>c</b> Protein expression of β-catenin and P-β-catenin protein in MDA-MB-231/Doc cells transfected with miR-3646 inhibitors, NC and blank control. <b>d</b> Relative mRNA expression of β-catenin in MDA-MB-231/S and MDA-MB-231/Doc cells (*<i>P</i><0.05). <b>e</b> Relative mRNA expression of β-catenin in MDA-MB-231/S cells transfected with miR-3646 mimics, NC and blank control (*<i>P</i><0.05). <b>f</b> Relative mRNA expression of β-catenin in MDA-MB-231/Doc cells transfected with miR-3646 inhibitors, NC and blank control (*<i>P</i><0.05).</p

Effect of miR-3646 mimics and miR-3646 inhibitors on the sensitivity of breast cancer cell lines to Doc.

<p><b>a,c</b> The IC50 value of Doc was determined after MDA-MB-231/S or MCF-7/S cells were transfected with miR-3646 mimics, NC or blank control for 48h using MTT assay (*<i>P</i><0.05). <b>b,d</b> After MDA-MB-231/Doc or MCF-7/S cells were transfected with miR-3646 inhibitors, NC or blank control for 48h, theIC50 value of Doc was determined by MTT assay (*<i>P</i><0.05).</p

Flow cytometry assessment of apoptotic MCF-7 cells induced by Doc was determined using APC Annexin V.

<p><b>a</b> The apoptotic rate and representative FACS figures in MCF-7/S cells transfected with miR-3646 mimics, NC and blank control (*<i>P</i><0.05). <b>b</b> The apoptotic rate and representative FACS figures in MCF-7/Doc cells transfected with miR-3646 inhibitors, NC and blank control (*<i>P</i><0.05).</p

Logistic Regression Analysis using serum protein concentration, before and after adjusting for covariates.

<p>Logistic Regression Analysis using serum protein concentration, before and after adjusting for covariates.</p