Shasha Du

IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures

Recently, the inflammatory cytokine IL-6 has been reported as a potent inducer of epithelial-mesenchymal transition (EMT) in breast cancer cells with an epithelial phenotype. Furthermore, EMT induces stem cell features in normal and transformed mammary cells. We explored whether IL-6-induced EMT promoted the generation of breast cancer stem-like cells (BrCSCs) in epithelial-like breast cancer cells, and whether the cytokines EGF and bFGF, analogous to IL-6, per se induced epithelial-mesenchymal transition, resulting in the enrichment of BrCSCs in mammosphere cultures. Herein, we provide evidence that IL-6 is capable of generating CD44+ cells with stem-like properties through induction of the EMT in the epithelial-like T47D breast cancer cells. We also show that mammosphere cultures of epithelial-like breast cancer cells, T47D, MCF7, ZR-75-1 and MDA-MB-453 cells, consistently generated stem-like cancer cells solely as a result of the EGF and bFGF cytokines in the mammosphere media mediating EMT. This finding demonstrated the link between the inflammatory cytokine IL-6 and BrCSCs and identified an important mechanism for the enrichment of BrCSCs in mammosphere cultures. Thus, EMT appears to be a critical mechanism for the induction of cancer cells with stem-like properties, and EMT of non-stem cancer cells could be a source of CSCs.

Robotic-assisted versus laparoscopic colorectal surgery: a meta-analysis of four randomized controlled trials

BackgroundRobotic-assisted laparoscopy is popularly performed for colorectal disease. The objective of this meta-analysis was to compare the safety and efficacy of robotic-assisted colorectal surgery (RCS) and laparoscopic colorectal surgery (LCS) for colorectal disease based on randomized controlled trial studies.MethodsLiterature searches of electronic databases (Pubmed, Web of Science, and Cochrane Library) were performed to identify randomized controlled trial studies that compared the clinical or oncologic outcomes of RCS and LCS. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were mean differences and odds ratios for continuous and dichotomous variables, respectively. Fixed-effects or random-effects models were adopted according to heterogeneity.ResultsFour randomized controlled trial studies were identified for this meta-analysis. In total, 110 patients underwent RCS, and 116 patients underwent LCS. The results revealed that estimated blood losses (EBLs), conversion rates and times to the recovery of bowel function were significantly reduced following RCS compared with LCS. There were no significant differences in complication rates, lengths of hospital stays, proximal margins, distal margins or harvested lymph nodes between the two techniques.ConclusionsRCS is a promising technique and is a safe and effective alternative to LCS for colorectal surgery. The advantages of RCS include reduced EBLs, lower conversion rates and shorter times to the recovery of bowel function. Further studies are required to define the financial effects of RCS and the effects of RCS on long-term oncologic outcomes.

MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1.

Radioresistance is a major challenge during the treatment of breast cancer. A further understanding of the mechanisms of radioresistance could provide strategies to address this challenge. In our study, we compared the expression of miR‐200c in four distinct breast cancer cell lines: two representative basal cancer cells (MDA‐MB‐231 and BT549) vs. two representative luminal cancer cells (MCF‐7 and BT474). The results revealed practically lower expression of miR‐200c in the two basal cancer cell lines and higher expression of miR‐200c in luminal cancer cells compared to the normal breast epithelial cell line MCF‐10A. Ectopic expression of miR‐200c in MDA‐MB‐231 cells inhibited irradiation‐induced autophagy and sensitized the breast cancer cells to irradiation. We also identified UBQLN1 as a direct functional target of miR‐200c involved in irradiation‐induced autophagy and radioresistance. In 35 human breast cancer tissue samples, we detected an inverse correlation between the expression of miR‐200c vs. UBQLN1 and LC3. These results indicate that the identified miR‐200c/UBQLN1‐mediated autophagy pathway may help to elucidate radioresistance in human breast cancer and might represent a therapeutic strategy.

Robotic versus Open Gastrectomy for Gastric Cancer: A Meta-Analysis

Aim To evaluate the safety and efficacy of robotic gastrectomy versus open gastrectomy for gastric cancer. Methods A comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Knowledge was performed. Systematic review was carried out to identify studies comparing robotic gastrectomy and open gastrectomy in gastric cancer. Intraoperative and postoperative outcomes were also analyzed to evaluate the safety and efficacy of the surgery. A fixed effects model or a random effects model was utilized according to the heterogeneity. Results Four studies involving 5780 patients with 520 (9.00%) cases of robotic gastrectomy and 5260 (91.00%) cases of open gastrectomy were included in this meta-analysis. Compared to open gastrectomy, robotic gastrectomy has a significantly longer operation time (weighted mean differences (WMD) =92.37, 95% confidence interval (CI): 55.63 to 129.12, P<0.00001), lower blood loss (WMD: -126.08, 95% CI: -189.02 to -63.13, P<0.0001), and shorter hospital stay (WMD = -2.87; 95% CI: -4.17 to -1.56; P<0.0001). No statistical difference was noted based on the rate of overall postoperative complication, wound infection, bleeding, number of harvested lymph nodes, anastomotic leakage and postoperative mortality rate. Conclusions The results of this meta-analysis suggest that robotic gastrectomy is a better alternative technique to open gastrectomy for gastric cancer. However, more prospective, well-designed, multicenter, randomized controlled trials are necessary to further evaluate the safety and efficacy as well as the long-term outcome.

Meta-analysis of Outcomes Compared between Robotic and Laparoscopic Gastrectomy for Gastric Cancer

This meta-analysis was performed to evaluate and compare the outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for treating gastric cancer. A systematic literature search was carried out using the PubMed database, Web of Knowledge, and the Cochrane Library database to obtain comparative studies assessing the safety and efficiency between RG and LG in May, 2013. Data of interest were analyzed by using of Review Manager version 5.2 software (Cochrane Collaboration). A fixed effects model or random effects model was applied according to heterogeneity. Seven papers reporting results that compared robotic gastrectomy with laparoscopic gastrectomy for gastric cancer were selected for this meta-analysis. Our meta- analysis included 2,235 patients with gastric cancer, of which 1,473 had undergone laparoscopic gastrectomy, and 762 had received robotic gastrectomy. Compared with laparoscopic gastrectomy, robotic gastrectomy was associated with longer operative time but less blood loss. There were no significant difference in terms of hospital stay, total postoperative complication rate, proximal margin, distal margin, numbers of harvested lymph nodes and mortality rate between robotic gastrectomy and laparoscopic gastrectomy. Our meta-analysis showed that robotic gastrectomy is a safe technique for treating gastric cancer that compares favorably with laparoscopic gastrectomy in short term outcomes. However, the long term outcomes between the two techniques need to be further examined.

MiR-451 increases radiosensitivity of nasopharyngeal carcinoma cells by targeting ras-related protein 14 (RAB14)

Radioresistance severely impedes the treatment of nasopharyngeal carcinoma (NPC). Recent evidence has shown that the abnormal expression of microRNAs (miRNAs) contributes to radiosensitivity. The aim of this study, therefore, was to investigate whether expression of the miRNAs correlated with radiosensitivity in the context of NPC. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantify miR-451 expression in two representative NPC cell lines. The role of miR-451 in NPC radiosensitivity was analyzed using a colony formation assay and an immunofluorescence assay with overexpression of miR-451 in NPC cells. Luciferase reporter assays, RT-PCR, and Western blot were performed to confirm the target of miR-451. High levels of miR-451 expression enhanced radiosensitivity in NPC cells by inhibiting the repair of irradiation-induced double-strand breaks (DSBs) and increasing apoptosis. The results also demonstrated that miR-451 directly targeted ras-related protein 14 (RAB14). Downregulation of RAB14 partially replicated the miR-451-mediated DSBs induced by ionizing radiation (IR). MiR-451 could be a potential target for enhancing radiosensitivity of NPC cells by targeting RAB14.

miR-101 sensitizes human nasopharyngeal carcinoma cells to radiation by targeting stathmin 1

Radioresistance remains a major problem in the treatment of patients suffering from nasopharyngeal carcinoma (NPC). A better understanding of the mechanisms involved in the induction of radioresistance may provide strategies to improve NPC patients’ response to therapy. The present study aimed to investigate the effect of microRNA (miR)-101 on the radioresistance of NPC cells. Analysis of miR-101 expression levels indicated that miR-101 was downregulated in NPC cell lines. Furthermore, ectopic expression of miR-101 suppressed cell proliferation and enhanced radiosensitivity of NPC cells. Stathmin 1 (STMN1) was additionally verified as a direct functional target of miR-101, which was found to be involved in cell viability, radioresistance and radiation-induced autophagy of NPC cells. In conclusions, the results of the present study suggested that the identified miR-101/STMN1 pathway contributed to the elucidation of the mechanisms of radioresistance in human NPC and that it may represent a potential therapeutic target.

Radiation-induced Cochlea hair cell death: mechanisms and protection.

Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini- review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC) , are claimed to be effective at reducing radiation- inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre- examined in order to minimize the damage to cochlea hair cells.

Protective effect of tanshinone IIA against radiation‑induced ototoxicity in HEI-OC1 cells

Radiotherapy is a highly efficient treatment method for nasopharyngeal carcinoma that is often accompanied by significant ototoxic side-effects. The inner ear hair cells are particularly prone to serious injury following radiotherapy. Tanshinone IIA is a transcription factor inhibitor that is extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge. The present study investigated the effects of tanshinone IIA treatment on radiation-induced toxicity in the HEI-OC1 hair cell line. Using an MTT assay and flow cytometry, the radiation-induced weakening of the cells was observed to be alleviated when the cells were pre-treated with tanshinone IIA. Radiation exposure promoted p65/nuclear factor (NF)-κB nuclear translocation and activated the p53/p21 pathway, two processes which play a significant role in radiation-induced cell apoptosis. However, pre-treatment of the cells with tanshinone IIA inhibited p65/NF-κB nuclear translocation and p53/p21 pathway activation. These results demonstrate that tanshinone IIA is capable of protecting cochlear cells from radiation-induced injury through the suppression of p65/NF-κB nuclear translocation and the p53/p21 signaling pathway.

Hypoxia-induced angiotensin II by the lactate-chymase-dependent mechanism mediates radioresistance of hypoxic tumor cells

The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism. We further demonstrate in nasopharyngeal carcinoma CNE2 and 5–8F cells that this chymase-dependent effect is mediated by increased levels of lactate, a by-product of glycolytic metabolism. Finally, we show that the enhanced angiotensin II plays an important role in the intracellular accumulation of HIF-1α of hypoxic nasopharyngeal carcinoma cells and mediates the radiation-resistant phenotype of these nasopharyngeal carcinoma cells. Thus, our findings reveal the critical role of hypoxia in producing local angiotensin II by a lactate-chymase-dependent mechanism and highlight the importance of local angiotensin II in regulating radioresistance of hypoxic tumor cells.