Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of ...HOTAIR in gastric carcinogenesis remains largely unknown.
HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis.
HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers.
HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.
MicroRNAs (miRNAs) are short, non-coding RNAs (~22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating gene expression. Although miR-196a has been implicated ...in several other cancers, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of miR-196a in NSCLC and its clinical significance, as well as its biological role in tumor progression.
Expression of miR-196a was analyzed in 34 NSCLC tissues and five NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of DNA methylation on miR-196a expression was investigated by 5-aza-2-deoxy-cytidine treatment and bisulfite sequencing. The effect of miR-196a on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Analysis of target protein expression was determined by western blotting. Luciferase reporter plasmids were constructed to confirm the action of miR-196a on downstream target genes, including HOXA5. Differences between the results were tested for significance using Student's t-test (two-tailed).
miR-196a was highly expressed both in NSCLC samples and cell lines compared with their corresponding normal counterparts, and the expression of miR-196a may be affected by DNA demethylation. Higher expression of miR-196a in NSCLC tissues was associated with a higher clinical stage, and also correlated with NSCLC lymph-node metastasis. In vitro functional assays demonstrated that modulation of miR-196a expression affected NSCLC cell proliferation, migration and invasion. Our analysis showed that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein levels, and luciferase assays confirmed that miR-196a directly bound to the 3'untranslated region of HOXA5. Knockdown of HOXA5 expression in A549 cells using RNAi was shown to promote NSCLC cell proliferation, migration and invasion. Finally, we observed an inverse correlation between HOXA5 and miR-196a expression in NSCLC tissues.
Our findings indicate that miR-196a is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell proliferation, migration and invasion, partially via the down-regulation of HOXA5. Thus, miR-196a may represent a potential therapeutic target for NSCLC intervention.
Reliable decision‐making in a safety‐critical system depends on the consistency of the state of the system process. Based on the decision‐makeing properties of safety‐critical systems, the definition ...of the critical component, Boolean evolution system, and cognate variables are presented here. By exploring the two lemmas of the critical components, the consistency of the safety‐critical system is defined, then a new process of a safety‐critical decision of consistency checking is proposed. In order to check the consistency properties of the decision, two computation tree logic formulas derived from the lemmas of the consistency checking are developed. The case of the train routing selection is modelled and verified by model checking, which shows the decision prototype guarantees the safety of the critical process. As the turnout is the critical component in the process of the train routing selection, a multi‐sensor‐based unit of state monitoring is developed, and a real‐world test shows the accuracy of the monitoring unit. This study confirms that the state consistency verification ensures the reliability of the safety‐critical system's decision output. The case can enlighten the development of the intelligent control system which has a critical component of decision‐making.
Large-scale sudden-onset disasters may cause massive injuries and thus place great pressure on the emergency blood supplies of local blood banks. When blood is in short supply, blood products ...gathered urgently to a local blood center should be appropriately allocated to blood banks in the affected area. Moreover, ABO/
Rh
(D) compatibilities among blood groups must be considered during emergency situations. To minimize the total unmet demand of blood products considering the optimal ABO/
Rh
(D)-compatible blood substitution scheme, a mixed integer programming model is developed and solved efficiently by using a greedy heuristic algorithm. Finally, a numerical example derived from the emergency blood supply scenario of the Wenchuan Earthquake is presented to verify the proposed model and algorithm. The results show that considering ABO/
Rh
(D)-compatible blood substitution can remarkably increase the efficiency of emergency blood allocation while lowering blood shortage, and the preference order of possible ABO/
Rh
(D)-compatible substitutions has an influence on the allocation solution.
Background
Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small‐molecule ...multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double‐blinded, placebo‐controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.
Methods
Famitinib or placebo was administered orally once daily. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality‐of‐life (QoL), and safety.
Results
Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand‐foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657).
Conclusion
Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.
Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO‐Gastrointestinal Symposium
The present study was approved by the Ethics Committee of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. ...the protrusion of zygomatic ...arch is slightly lowered and temporal depression is filled in one operation. Dr. Ji-Guang Ma, 17th Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Badachu Road, No. 33, Shijingshan District, Beijing 100041, ChinaE-Mail: majiguang@psh.pumc.edu.cn How to cite this article:
Long non-coding RNAs (lncRNAs) are characterized as key layers of the genome in various cancers. TSPEAR-AS2 was highlighted to be a candidate lncRNA potentially involved in gastric cancer (GC) ...progression. However, the clinical significance and mechanism of TSPEAR-AS2 in GC required clarification. The clinical significance of TSPEAR-AS2 was elucidated through Kaplan-Meier Plotter. The mechanism of TSPEAR-AS2 in GC was clarified in vitro and in vivo using luciferase reporter, chromatin immunoprecipitation, RNA immunoprecipitation assays, and animal models. TSPEAR-AS2 elevation was closely correlated with overall survival of GC patients. A basic transcription element-binding protein 2 (BTEB2)-activated TSPEAR-AS2 model was first explored in this study. TSPEAR-AS2 silencing substantially reduced tumorigenic capacities of GC cells, while TSPEAR-AS2 elevation had the opposite effect. Mechanistically, TSPEAR-AS2 bound with both polycomb repressive complex 2 (PRC2) and argonaute 2 (Ago2). TSPEAR-AS2 knockdown significantly decreased H3K27me3 levels at promoter regions of gap junction protein alpha 1 (GJA1). Ago2 was recruited by TSPEAR-AS2, which was defined to sponge miR-1207-5p, contributing to the repression of claudin 4 (CLDN4) translation. The axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 plays an important role in GC progression, suggesting a new therapeutic direction in GC treatment.
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Ma and colleagues elucidated the clinical significance and mechanism of lncRNA TSPEAR-AS2 in gastric cancer progression. The regulatory axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 suggested a new therapeutic direction for patients with gastric cancer.
The Solitaire AB stent is one of many assistant stents used for treating wide-necked cerebral aneurysm, and has been used since 2003. However, large sample studies on its safety and effectiveness are ...lacking. The objective of this study was to evaluate the effectiveness and safety of the Solitaire AB stent in the coil embolization of wide-necked cerebral aneurysms.
Retrospective review of the clinical and image data of 116 patients with wide-necked cerebral aneurysms who had been enrolled at six interventional neuroradiology centers from February 2010 to February 2014 and had been treated by coil embolization; in total, 120 Solitaire AB stents were used. The degree of aneurysm occlusion was examined using digital subtraction angiography (DSA) immediately after the procedure and during follow-up, and was graded using the modified Raymond classification. We also observed complications to evaluate the safety and effectiveness of this therapy.
The 120 Solitaire AB stents (4 mm × 15 mm, four stents; 4 mm × 20 mm, 16 stents; 6 mm × 20 mm, 36 stents; 6 mm × 30 mm, 64 stents) were inserted to treat 120 wide-necked cerebral aneurysms. All stents were inserted successfully. DSA immediately post-surgery revealed 55 cases of complete occlusion, 59 cases of neck remnant, and six cases of aneurysm remnant. Perioperatively, there were four cases of hemorrhage and four cases of stent thrombosis. The follow-up spanned 3-37 months; of 92 patients examined by DSA at the 6-month follow up, 12 had disease recurrence.
The Solitaire AB stent is effective with a good technical success rate and short-term effect for assisting coil embolization of wide-necked cerebral aneurysms.
As one of most efficient techniques for material-property modification, ion implantation has shown its unique ability for alteration of surface refractive index of a large number of optical ...materials, forming waveguide structures. The induced refractive index changes are materials related, and closely dependent on the species, energies and doses of the implanted ions. This paper reviews the results of recent research on the fabrication, investigation and applications of the ion-implanted optical waveguides in various optical materials, including crystals and non-crystalline glasses. As will be summarized, ion implantation offers a nearly universal solution for the waveguide fabrication in most existing optical materials to date, which opens up new possibilities of attractive optical applications.
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