Nuclear Her2 contributes to paclitaxel resistance in breast cancer cells.

Translocation of full-length Her2 receptor into nucleus was reported by some studies. Here, we tested whether nuclear Her2 contributes to paclitaxel resistance in Her2-overexpressing breast cancer cells. Breast cancer cell was transfected with plasmids containing cDNA of wild-type Her2 or mutant-type Her2 lacking the nuclear localization signal (NLS) sequence which is required for Her2 nuclear transport. Cell resistance to paclitaxel was analyzed. Paclitaxel-resistant breast cancer cell was also developed and nuclear Her2 expression was tested. Then, correlation between nuclear Her2 and resistance to paclitaxel were analyzed. Expression of importin ß1 was decreased to downregulate nuclear Her2 level and cell resistance to paclitaxel was tested. We found that Her2 overexpression increases Her2 nuclear expression and cells resistance to paclitaxel in MCF-7 cells. In the paclitaxel resistant cell (SK-BR-3/R), nuclear Her2 expression is upregulated compared with parental SK-BR-3 cells. Increased expression of nuclear Her2 after short-time (48 h) treatment of paclitaxel was also observed in SK-BR-3 cells. Further downregulation of Her2 nuclear expression through blocking expression of importin ß1 sensitizes the cells to paclitaxel. The analysis showed that the Her2 nuclear expression increases the survivin expression which leads to resistance to paclitaxel. Her2 nuclear expression decreases paclitaxel-induced apoptosis. However, co-immunoprecipitation was applied, and the physical interaction of nuclear Her2 and survivin was not detected. We show for the first time that nuclear Her2 contributes to paclitaxel resistance in breast cancer cells which suggests that nuclear Her2 as a potential target to sensitize breast cancers to paclitaxel treatment.

Identification of potential core genes in triple negative breast cancer using bioinformatics analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome and limited treatment options. Lacking molecular targets, chemotherapy is the main adjuvant treatment for TNBC patients. MATERIALS AND METHODS: To explore potential therapeutic targets for TNBC, we analyzed three microarray datasets (GSE38959, GSE45827, and GSE65194) derived from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between TNBC and normal tissue. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery to identify the pathways and functional annotation of DEGs. Protein-protein interaction of these DEGs was analyzed based on the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape software. In addition, we used the online Kaplan-Meier plotter survival analysis tool to evaluate the prognostic value of hub genes expression in breast cancer patients. RESULTS: A total of 278 upregulated DEGs and 173 downregulated DEGs were identified. Among them, ten hub genes with a high degree of connectivity were picked out. Overexpression of these hub genes was associated with unfavorable prognosis of breast cancer, especially, CCNB1 overexpression was observed and indicated poor outcome of TNBC. CONCLUSION: Our study suggests that CCNB1 was overexpressed in TNBC compared with normal breast tissue, and overexpression of CCNB1 was an unfavorable prognostic factor of TNBC patients. Further study is needed to explore the value of CCNB1 in the treatment of TNBC.

Is laparoscopic appendectomy feasible for complicated appendicitis ?A systematic review and meta-analysis.

BACKGROUND: laparoscopic appendectomy(LA) has proved to be a safe alternative to open appendectomy(OA) in uncomplicated appendicitis; however, the feasibility of LA for complicated appendicitis(CA) has not been conclusively determined. OBJECTIVES: To assess the feasibility and safety of LA for CA through a systematic review and meta-analysis. METHODS: A literature search in PubMed, Embase, Cochrane Library, and web of Science was performed for eligible studies published from the inception of the databases to January 2016. All studies comparing LA and OA for CA were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently, and meta-analysis was conducted using Revman software, vision 5.2. RESULTS: Two randomized controlled trials (RCTs) and 14 retrospective cohort studies(RCSs) were finally identified. Our meta-analysis showed that LA for CA could reduce the rate of surgical site infections (SSIs) (OR = 0.28; 95% CI: 0.25 to0.31, P < 0.00001), but LA did not increase the rate of postoperative intra-abdominal abscess(IAA) (OR = 0.79; 95% CI: 0.45 to 1.34, P = 0.40). The results showed that the operating time in the LA groups was much longer than that in the OA groups (WMD = 13.78, 95% CI: 8.99 to 18.57, P < 0.00001). However, the length of hospital stays in the LA groups were significantly shorter than those in the OA groups (WMD = -2.47, 95%CI: -3.75 to -1.19, P < 0.0002), and the time until oral intake(TTOI) was much earlier in the LA groups than in the OA groups (WMD = -0.88, 95% CI: -1.20 to -0.55, P < 0.00001). No significant difference was observed in the times of postoperative analgesia between the two groups(P > 0.05). CONCLUSION: LA was feasible and safe for complicated appendicitis, and it not only could shorten the hospital stays and the time until oral intake, but it could also reduce the risk of surgical site infection.

Effect of BRCA2 mutation on familial breast cancer survival: A systematic review and meta-analysis.

Reports of BRCA2 genetic mutations on the prognosis of familial breast cancer (BC) patients have been contradictory. True difference in survival, if it exists, would have important implications for genetic counseling and in treatment of hereditary BC. The purpose of this study was to compare overall survival rate (OSR) among BRCA2 mutation carriers, non-carriers and sporadic BC patients. We searched the PUBMED and EMBASE databases and retrieved 4529 articles using keywords that included breast cancer, BRCA, prognosis and survival. Nine articles were selected for systematic review and among them 6 were included in our meta-analysis. We used the fixed and random effect models to calculate the summary odds ratio (OR) and corresponding 95% confidence interval (CI). BRCA2 mutation carriers had significantly higher long-term OSR than non-carriers (OR=0.69 [95% CI=0.5-0.95]), while both short-term and long-term OSR of BRCA2 mutation carriers did not differ from those of patients with sporadic disease (OR=1.11 [95% CI=0.74-1.65]; 0.85 [95% CI=0.38-1.94], respectively). For BC-specific survival rate (BCSSR), BRCA2 mutation carriers had a similar BCSSR to the non-carriers (OR=0.61 [95% CI=0.28-1.34]). There was no significant difference in disease-free survival (DFS) between BRCA2 mutation carriers and patients with sporadic disease. Our results suggest that BRCA2 mutation increases long-term OSR in hereditary BC, which reminds us a new prospect of management of the disease.