Long intergenic noncoding RNA-p21 inhibits apoptosis by decreasing PUMA expression in non-small cell lung cancer.

OBJECTIVE: Long noncoding RNAs (lncRNAs) are important mediators in tumor progression. Long intergenic noncoding RNA-p21 (lincRNA-p21) participates in multiple biological processes. This study explored the role of lincRNA-p21 in human non-small cell lung cancer (NSCLC) progression and potential regulatory mechanisms. METHODS: LincRNA-p21 expression in NSCLC tissues and cell lines (A549, H1299, H1650, and NCI-H2087) was determined by quantitative real-time PCR. LincRNA-p21 overexpressing and sh-lincRNA-p21 lentiviral were respectively transfected into H1299 and A549 cells. Flow cytometry was used to measure apoptosis. Microarray analysis and RNA pull-down assay were used to predict the target genes of lincRNA-p21. Finally, PUMA siRNA and overexpressing PUMA were transfected into NSCLC cells, and the extent of cell apoptosis was measured. The protein expression levels of the relative genes were confirmed by western blot analysis. RESULTS: LincRNA-p21 was significantly upregulated in NSCLC tissues and cells. The upregulation of lincRNA-p21 considerably inhibited cell apoptosis while the downregulation of lincRNA-p21 showed the opposite effect. PUMA was a direct target gene of lincRNA-p21 and was negatively correlated with lincRNA-p21 in NSCLC specimens. The anti-apoptotic effect of lincRNA-p21 can be effectively attenuated by the upregulation of PUMA. CONCLUSION: LincRNA-p21 is aberrantly upregulated in NSCLC and inhibits cell apoptosis by decreasing PUMA expression.

Inhibition of Hes1 enhances lapatinib sensitivity in gastric cancer sphere-forming cells.

It has been considered that the neurogenic locus notch homolog protein (Notch) signaling pathway serves an essential role in cellular differentiation, proliferation and apoptosis. However, the function of the Notch signaling pathway in gastric cancer stem cells (GCSCs) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity remains unclear. The present study aimed to delineate the role of the Notch1 signaling pathway in GCSCs and lapatinib sensitivity. Sphere-forming cells were separated from human gastric cancer MKN45 parental cells. The sphere-forming cells exhibited characteristics of CSCs and higher Notch1 expression compared with that of parental cells. To investigate the role of the Notch1 signaling pathway in GCSCs, the expression of transcription factor Hes1 (Hes1) was knocked down using small interfering RNA against Hes1. It was observed that Hes1 expression was significantly downregulated in knocked down cells. The inhibition of Hes1 suppressed the properties of CSCs, as indicated by significant decreases in the expression of the transcription factor sex determining region Y-box 2, epithelial cell adhesion molecule and the homeobox protein Nanog and reduced spheroid colony formation. In addition, epithelial-mesenchymal transition was significantly impaired in sphere-forming cells following Hes1 knockdown. Furthermore, the inhibition of Hes1 effectively enhanced lapatinib sensitivity in sphere-forming cells. These results suggest that sphere-forming gastric cancer cells possess the characteristics of CSCs, and that the Notch1 signaling pathway serves an essential role in the maintenance of CSCs and lapatinib sensitivity.

Pregabalin can decrease acute pain and postoperative nausea and vomiting in hysterectomy: A meta-analysis.

BACKGROUND: Whether the preoperative administration of pregabalin plays a beneficial role in controlling acute pain after hysterectomy is unknown. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the efficacy and safety of the preoperative use of pregabalin to treat acute postoperative pain following hysterectomy. METHODS: In April 2017, a systematic computer-based search was conducted in the PubMed, EMBASE, Web of Science, Cochrane Library, and Google databases. RCTs comparing pregabalin with placebo in patients undergoing hysterectomy were retrieved. The primary endpoint was the visual analog scale (VAS) score with rest or mobilization at 2 h, 4 and 24 hours and cumulative morphine consumption at 2, 4, 24, and 48 hours. The secondary outcomes were complications of nausea, vomiting, sedation, and dizziness. After tests for publication bias and heterogeneity among studies were performed, the data were aggregated for random-effects models when necessary. RESULTS: Ten clinical studies with 1207 patients (pregabalin = 760, control = 447) were finally included in this meta-analysis. Preoperative administration of pregabalin was associated with a significant reduction of VAS with rest or mobilization at 2, 4, and 24 hours after hysterectomy. Further, the preoperative administration of pregabalin was associated with a reduction in total morphine consumption at 2, 4, 24, and 48 hours after hysterectomy. The occurrence of morphine-related complications (nausea and vomiting) was also reduced in the pregabalin group. However, the preoperative administration of pregabalin was associated with an increase in the occurrence of dizziness. There was no significant difference in the occurrence of sedation. CONCLUSIONS: The preoperative use of pregabalin reduced postoperative pain, total morphine consumption, and morphine-related complications following hysterectomy. The doses of pregabalin were different, and large heterogeneity was the limitation of the current meta-analysis. Further studies should determine the optimal dose for controlling acute pain after hysterectomy.

[Clinical Efficacy of Cellular Immuotherapy Combined with Bortezomib for the Treatment of Patients with Multiple Myeloma].

OBJECTIVE: To study the clinical efficacy of cellular immunotherapy combined with bortezomib for treatment of patients with multiple myeloma. METHODS: A total of 76 patients with multiple myeloma in our hospital from October 2012 to October 2013 were selected and randomly divided into 2 groups: the patients in 1 group (38 cases) were treated with cellular immunotherapy combined with chemotherapy including bortezomib (combined therapy group), the patients in other group(38 cases) were treated with only chemotherapy including bortezomib(single chemotherapy as control group). The treatment remission rate, the expression changes of immunophenotype, progression-free survival(PFS) and adverse reactions were compared in the 2 groups. RESULTS: The total remission rate of combined therapy group was significantly higher than that in the control group (P<0.05); the positive rates of CD38+, CD56+ and CD138+ in combined therapy group were all significantly lower than those in control group, and the CD19+ was significantly higher (P<0.05). The PFS rates of 1, 2 and 3 years in the combined therapy group were all significantly higher than those in the control group (P<0.05). The incidence of fatigue, rash, peripheral neuropathy, anemia and granulocyte deficiency in the combined therapy group was all significantly lower than that in the control group (P<0.05). CONCLUSION: Cellular immunotherapy combined with bortezomib can significantly improve the remission rate, prolong survival, and significantly decrease adverse event rate of multiple myeloma patients.

Silencing of ATM expression by siRNA technique contributes to glioma stem cell radiosensitivity in vitro and in vivo.

Evidence has shown that both high expression of the ataxia-telangiectasia mutated (ATM) gene and glioma stem cells (GSCs) are responsible for radioresistance in glioma. Thus, we hypothesized that brain tumor radiosensitivity may be enhanced via silencing of the ATM gene in GSCs. In the present study we successfully induced GSCs from two cell lines and used CD133 and nestin to identify GSCs. A lentivirus was used to deliver siRNA-ATMPuro (A group) to GSCs prior to radiation, while siRNA-HKPuro (N group) and GSCs (C group) were used as negative and blank controls, respectively. RT-qPCR and western blotting were performed to verify the efficiency of the siRNA-ATM technique. The expression of the ATM gene and ATM protein were significantly downregulated post-transfection. Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that the A group demonstrated weak cell proliferation and lower survival fractions post-irradiation compared to the C/N groups. Flow cytometry was used to examine the percentage of cell apoptosis and G2 phase arrest, which were both higher in the A group than in the C/N groups. We found that the comet tail percentage evaluated by comet assay was higher in the A group than in the C/N groups. After radiation treatment, three radiosensitive genes [p53, proliferating cell nuclear antigen (PCNA), survivin] exhibited a decreasing tendency as determined by RT-qPCR. Mice underwent subcutaneous implantation, followed by radiation, and the resulting necrosis and hemorrhage were more obvious in the A group than in the N groups. In conclusion, silencing of ATM via the siRNA technique improved radiosensitivity of GSCs both in vitro and in vivo.

Hsa_circ_0101996 combined with hsa_circ_0101119 in peripheral whole blood can serve as the potential biomarkers for human cervical squamous cell carcinoma.

BACKGROUND: Previous study suggests changes in circRNAs in tumor tissues from cervical squamous cell carcinoma (CSCC) patients. However, little is known about the diagnostic value of circRNAs in CSCC. To assess the potential application of circRNAs as diagnostic tools in CSCC, the circulating circRNAs in peripheral whole blood were carried out. METHODS: Five up-regulated circRNAs in peripheral whole blood from 87 patients with CSCC and 55 healthy controls were first identified by real-time quantitative polymerase chain reaction (RT-qPCR). The diagnostic value was evaluated using receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC). RESULTS: Compared with healthy controls, hsa_circ_0101996, hsa_circ_0104649, hsa_circ_0104443 and hsa_circ_0101119 expression were significantly up-regulated in peripheral whole blood from CSCC patients. ROC analysis showed that hsa_circ_0101996 and hsa_circ_0101119 could distinguish CSCC patients from healthy controls with high AUC (0.906 and 0.887, respectively). Intriguingly, the combination of hsa_circ_0101996 and hsa_circ_0101119 markedly improved AUC (0.964). CONCLUSION: All of the findings suggest that hsa_circ_0101996 combined with hsa_circ_0101119 can serve as potential biomarkers for CSCC detection.

Gastric tumor-initiating CD44+ cells and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT.

It has been proposed that the Notch signaling pathway may serve a pivotal role in cellular differentiation, proliferation and apoptosis. However, the function of Notch signaling in gastric cancer stem cells (GCSCs) is largely unknown. The present study aimed to delineate the role of the Notch1 pathway in GCSCs and during epithelial-mesenchymal transition (EMT). Flow cytometry was used to isolate CD44+ cells from the human gastric cancer cell line, MKN45. CD44+ cells displayed the characteristics of CSCs and exhibited higher Notch1 expression compared with CD44- cells. To investigate the role of the Notch1 pathway in GCSCs, CD44+ cells were treated with the γ-secretase inhibitor DAPT. DAPT treatment inhibited the expression of the Notch1 downstream target Hes1 and EMT markers, suppressed the properties of CSCs and impaired the invasion and proliferation capabilities of CD44+ cells. In addition, intraperitoneal treatment with DAPT effectively inhibited the growth of CD44+ cell xenograft tumors. The present study indicated that CD44+ GCSCs possess the characteristics of CSCs and that the Notch1 pathway serves a critical role in the maintenance of CSCs and EMT.

miR-223 functions as a potent tumor suppressor of the Lewis lung carcinoma cell line by targeting insulin-like growth factor-1 receptor and cyclin-dependent kinase 2.

microRNAs (miRNAs) have been hypothesized to function as oncogenes or tumor suppressors by targeting specific cancer-related genes. Previous studies have reported that miR-223 may serve as a tumor suppressor in a number of cancer types, however, knowledge of its targets in non-small cell lung cancer (NSCLC) remains limited. In the current study, miR-223 was found to inhibit cell proliferation in vitro by CCK-8 assay, growth curves and an anchorage-independent growth assay in a Lewis lung carcinoma (LLC) cell line. miR-223 transfection in the LLC cells was observed to significantly inhibit migration and invasion, induce G2/M arrest and decrease the expression levels of Sca-1, a marker of murine stem cells. In addition, miR-223 transfection markedly suppressed AKT and ERK signaling, as well as insulin-like growth factor-1 receptor (IGF-1R)-mediated downstream signaling, pathways that are crucial for cell proliferation and invasion in NSCLC cells. Analyses in C57BL/6 mice demonstrated that miR-223 suppresses tumorigenicity in vivo. Using a luciferase activity assay and western blot analysis, IGF-1R and cyclin-dependent kinase 2 (CDK2) were identified as direct targets of miR-223. In the present study, novel cancer-related targets of miR-223 were identified and verified in a LLC cell line, indicating that miR-223 functions as a tumor suppressor, which may fine-tune the activity of the IGF-1R pathway in lung cancer. Therefore, increasing miR-223 expression may provide a novel approach for the treatment of NSCLC.

[Therapeutic and adverse effects of topotecan combined with cisplatin for treatment of advanced squamous cell lung cancer and head and neck cancer].

OBJECTIVE: To evaluate the therapeutic and adverse effects of topotecan combined with cisplatin in the treatment of advanced squamous cell lung cancer and head and neck cancer. METHODS: Totally 126 patients with advanced squamous cell lung cancer and head and neck cancer, which were confirmed by tissue pathology or cytopathology, were treated with intravenous infusion of topotecan at the dose of 0.75-1.2 mg/m2 (for 5 consecutive days) combined with intravenous infusion of cisplantin at 25-30 mg/m2 for 3 consecutive days. Each treatment course consisted of two 21-day cycles of the treatment. RESULTS: No complete remission was achieved in these patients, and 61 patients had partial remission, 53 had clinically stabilized disease and 12 had progressive disease. The total response rate was 48.4% among the patients, with the median survival time of 10.1 months and one-year survival rate of 36.7%. The major adverse effects were bone marrow suppression and alopecia. CONCLUSION: Topotecan combined with cisplatin may achieve a favorable response in patients with advanced squamous cell lung cancer and head and neck cancer, and causes tolerable adverse effect without accumulative toxicity.