Breast cancer is a malignant tumor that is harmful to women's health around the world. Investigating the biological mechanism is, therefore, of pivotal importance to improve patients' prognoses. Compared to non-neoplastic tissues, enhanced glucose and lipid metabolism is one of the most common properties of malignant breast cancer. Adenosine triphosphate (ATP) citrate lyase is a key enzyme linking aerobic glycolysis and fatty acid synthesis and is of high biological and prognostic significance in breast cancer. In our clinical study, fresh clinical tissues were used to analyze ATP citrate lyase expression by western blotting, and paraffin archived samples from 62 breast cancer patients were used to analyze ATP citrate lyase expression by immunohistochemistry. In the cellular study, following small interfering RNA-mediated inhibition of ATP citrate lyase in MCF-7 cells, cell viability and apoptosis were measured using the Cell Counting Kit-8 and flow cytometry, respectively. Breast cancer tissues showed strong expression of ATP citrate lyase, whereas adjacent normal tissues showed weak expression. Silencing of endogenous ATP citrate lyase expression by small interfering RNA in MCF-7 cells suppressed cell viability and increased cell apoptosis. Collectively, our study revealed that expression of ATP citrate lyase was significantly increased in breast cancer tissue compared with normal tissue. In addition, we found that depletion of ATP citrate lyase suppressed tumor growth, which suggests that ATP citrate lyase-related inhibitors might be potential therapeutic approaches for breast cancer.

BackgroundRecent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4.MethodsWestern blot, Real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) were used to detect the expression of LAMA4 in TNBC. The effects of LAMA4 on TNBC cell proliferation, migration and invasion were also explored in vitro. The potential miRNA that targets LAMA4 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis.ResultsOur study showed LAMA4 mRNA (p = 0.001) and protein (p = 0.005) expression in TNBC tissue samples were elevated compared with adjacent normal tissue samples, and LAMA4 was mainly expressed in the cytoplasm of breast carcinoma cells. Knockdown of LAMA4 inhibited TNBC cell proliferation, migration and invasion in vitro. Moreover, further study revealed that LAMA4 was a putative target of miR-539, and miR-539 negatively regulated LAMA4 expression by directly targeting its 3′-UTR.ConclusionsOur study suggested that miR-539 suppressed the expression of LAMA4. LAMA4 plays an important role in tumor progression and may be an important target in treatment of TNBC.

Objectives:To compare laparoscopic extraperitoneal colostomy with transperitoneal colostomy for construction of a permanent stoma by measuring the incidence of parastomal hernia, and other postoperative complications related to colostomy.Methods:The meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China in 2014. A literature search of Medline, EMBASE, Cochrane database, and the Chinese Biomedical Literature Database (CBM) from the years 1990 to 2014 was performed. The literature searches were carried out using medical subject headings and free-text words: extraperitoneal colostomy, transperitoneal colostomy, laparoscopic extraperitoneal colostomy, rectal cancer, laparoscopic abdominoperineal resection, parastomal hernia, permanent stoma, and colostomy-related complications. Two different reviewers carried out the search and evaluated studies independently.Results:One randomized controlled trial and 6 retrospective studies were included. A total of 378 patients (209 extraperitoneal colostomy and 169 transperitoneal colostomy) were identified. Our analysis showed that there was a significantly lower rate of parastomal hernia (odds ratio 0.10; 95% confidence interval 0.03-0.29, p<0.0001) in the extraperitoneal colostomy group. However, the other stoma-related complications were not significantly different between the 2 groups.Conclusion:Colostomy construction via the extraperitoneal route using a laparoscopic approach can largely reduce the incidence of parastomal hernia. Laparoscopic permanent sigmoid stoma creation through the extraperitoneal route should be the first choice after laparoscopic abdominoperineal resection.

Breast cancer is a prevalent malignant cancer worldwide, and a lack of defined biomarkers for early prognostication contributes to its high associated mortality rate, especially in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. In the present study, HER-2 mRNA levels in patients were detected prior to surgery and during neoadjuvant chemotherapy to explore its potential diagnostic and prognostic value. Blood samples were collected from 70 patients with breast cancer, including 50 HER-2-negative and 20 HER-2-positive patients, prior to and following surgery (postoperative, n=13; neoadjuvant chemotherapy, n=5); the control group included 35 samples from healthy individuals. The relative mRNA level of HER-2 in blood was determined by one-step reverse transcription-quantitative polymerase chain reaction. HER-2 expression curves of measurements taken during neoadjuvant chemotherapy were compared with the tumor size. A significant difference in the blood HER-2 mRNA level was observed between healthy women and patients with breast cancer (P<0.0001). A cutoff value of 1.512 was established for the circulating HER-2 level in healthy subjects based on the upper 95% confidence interval value of samples from the control group. The level of HER-2 mRNA in blood was associated with the HER-2 status, Ki-67 expression, and lymphovascular invasion in primary tumor tissue samples; however, there was no association with the lymph node status, tumor stage, tumor grade, tumor size, patient age, estrogen or progesterone receptor status of the primary tumor. HER-2 mRNA levels were associated with the response rate, as determined by primary tumor size, in patients who received neoadjuvant chemotherapy. In conclusion, baseline and early changes in peripheral blood HER-2 mRNA indicated that HER-2 mRNA may be a potential diagnostic biomarker for breast cancer and a prognostic marker for predicting the efficacy of neoadjuvant therapy.

The aim of this study was to evaluate the procedure for and efficacy of endoscopic subcutaneous mastectomy for gynecomastia. Endoscopic subcutaneous mastectomy was performed on 100 benign, palpable breast enlargements in 58 male patients who were followed-up for 15–63 months. The surgery was conducted with the insufflation of CO2 subdermally. No cases were converted to open surgery. The unilateral surgery time was 70–90 min. The mean volume of the resected tissue was 200 ml. All procedures were completed successfully, with satisfactory clinical effects and ideal esthetic results postoperatively. There were three cases (3%) of papillary epidermal partial necrosis; following removal of the dressing during the hospital stay, normal nipple sensation returned. Endoscopic subcutaneous mastectomy had good clinical effects and ideal cosmetic results and is an appropriate approach for gynecomastia.

ABSTRACT. The study aimed to investigate the bio-distribution and radio-immuno-imaging features of

The resistance of breast cancer to radiotherapy remains a major obstacle to successful cancer management. Radiotherapy may result in DNA damage and activate breast cancer stem cells. DNA damage may lead to activation of the checkpoint kinase (CHK) signaling pathway, of which debromohymenialdisine (DBH) is a specific inhibitor. Radiotherapy also increases the expression of phosphorylated CHK1/2 (pCHK1/2) in the breast cancer cell line, MCF-7, in vitro in a dose-dependent manner. DBH is a relatively stable effective inhibitor that significantly reduces pCHK1/2 expression and MCF-7 proliferation. Low-dose radiotherapy combined with DBH resulted in a higher MCF-7 inhibition rate compared with high-dose radiation alone. This result indicates that the inhibition of the CHK1/2 signal pathway may significantly reduce DNA damage within radiated cells. Radiotherapy may also regulate the proportion of CD44+/CD24− MCF-7 cancer stem cells in a dose- and time-dependent manner. However, the stem cell proportion of MCF-7 cells was significantly reduced by treatment with DBH. The inhibition is relatively stable and time dependent. Significant reductions were observed after 3 days of culture (P<0.01). The results of the present study indicate that the DBH-induced downregulation of CHK may provide a novel method of enhancing the effect of radiotherapy and reducing stem cell survival in the MCF-7 cell line.

Colorectal cancer (CRC) is a major cause of cancer-related mortality. The aberrant expression of long non-coding RNAs (lncRNAs) is implicated in the pathogenesis of CRC. The present study investigated the role of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in CRC. lncRNA NEAT1 expression was detected in CRC tissues and cell lines. HCT116 cells were transfected with si-NEAT1, and the malignant behavior of the cells was detected. The binding associations between NEAT1 and E2F1, as well as between E2F1 and KDM5A were verified. si-NEAT1-transfected cells were also transfected with si-KDM5A. H3K4me3 methylation and cullin 4A (Cul4A) expression in HCT116 cells were detected. The si-NEAT1-transfected cells were also transfected with pc-Cul4A. Proteins related to the Wnt pathway were detected. A xenograft model of CRC using nude mice was established and the mice were injected with si-NEAT1-transfected HCT116 cells. lncRNA NEAT1 was found to be upregulated in CRC tissues and cells. NEAT1 silencing inhibited the malignant behaviors of the HCT116 cells. lncRNA NEAT1 inhibited KDM5A expression by binding to E2F1. The downregulation of KDM5A reversed the inhibitory effects of NEAT1 silencing on the malignant behavior of the cells. KDM5A inhibited Cul4A expression via the demethylation of H3K4me3. The overexpression of Cul4A promoted the malignant behavior of the si-NEAT1-transfected HCT116 cells. lncRNA NEAT1 activated the Wnt pathway via KDM5A/Cul4A. In vivo experiments confirmed the role of NEAT1 in CRC. On the whole, the present study demonstrates that lncRNA NEAT1 facilitates the progression of CRC via the KDM5A/Cul4A/Wnt axis.