LINC01354/microRNA-216b/KRAS Axis Promotes the Occurrence and Metastasis of Endometrial Cancer.

OBJECTIVE: LINC01354 has been defined as a tumor driver in several cancers. Nevertheless, whether LINC01354 involves in endometrial cancer (EC) has been little navigated. Thus, the mechanism of LINC01354 was explored in the disease. METHODS: Measurements of LINC01354, microRNA (miR)-216b and kirsten rat sarcoma viral oncogene (KRAS) levels in EC tissues and cells were performed. LINC01354 low expression and miR-216b overexpression vectors were introduced into EC cells (lshikawa), thereby their effects on cell viability, apoptosis, migration and invasion were manifested. Rescue experiments were also carried out by down-regulating LINC01354 and miR-216b spontaneously. Tumorigenesis in vivo was also assessed. The relationships of LINC01354/miR-216b/KRAS were analyzed. RESULTS: Increased LINC01354 and KRAS and reduced miR-216b levels were measured in EC. Silencing LINC01354 or overexpressing miR-216b retarded EC cellular development. LINC01354 counteracted with miR-216b to target KRAS. Suppression of miR-216b antagonized silenced LINC01354-induced impacts on EC cell development. LINC01354/miR-216b/KRAS axis enhanced tumorigenesis in mice with EC. CONCLUSION: It is testified that silencing LINC01354 inhibits KRAS by up-regulating miR-216b, thereby discouraging cell malignant phenotype in EC.

[Pilose antler polypeptide CNT14 promoted proliferation and migration of human oral mucosa fibroblast cells].

PURPOSE: To explore the effect of pilose antler polypeptides CNT14 on proliferation and migration of human oral mucosa fibroblast (hOMF) cells and the related molecular mechanism. METHODS: The biosafety of pilose antler polypeptides CNT14 on hOMF cells was verified by live-dead cell staining kit.CCK-8 assay was used to detect the effect of pilose antler polypeptides CNT14 on hOMF cell proliferation. The effect of pilose antler polypeptides CNT14 on hOMF cell migration was detected by scratch test. Western blot was used to detect the expression of α-SMA, TGF-ß1, Smad2 and p-Smad2 proteins in hOMF cells stimulated by pilose antler polypeptides CNT14. The effect of Smad2 inhibitors on fibroblast activation induced by pilose antler polypeptides CNT14 was evaluated.The model of keratinized gingival defect was established in New Zealand white rabbits, and the regenerated gingival tissue was stained with H-E. The expression levels of α-SMA, TGF-ß1, Smad2 and p-Smad2 proteins in the gingival tissues of regenerated New Zealand white rabbits were detected by immunohistochemistry, and the ability of pilose antler polypeptides CNT14 to promote regeneration of oral gingival tissues was verified. Statistical analysis was performed with SPSS 20.0 software package. RESULTS: The survival rate of hOMF cells was above 95% after treated with pilose antler polypeptides CNT14. After stimulation of hOMF cells with pilose antler polypeptides CNT14, the proliferation and migration rates of hOMF cells were increased compared with the control group (P＜0.05). The expression of α-SMA, TGF-ß1, Smad2 and p-Smad2 proteins in hOMF cells stimulated by pilose antler peptide CNT14 was increased, and the difference was statistically significant(P＜0.05). The expression of α-SMA in fibroblasts induced by Smad2 inhibitor was decreased. In animal experiments, H-E staining showed that the inflammatory response of oral mucosal wounds of New Zealand white rabbits treated with CNT14 was less than that of the control group. Immunohistochemical staining results showed that the expressions of α-SMA, TGF-ß1, Smad2 and p-Smad2 in the regenerated gingival tissues of New Zealand white rabbits treated with CNT14 were significantly increased compared with those in the control group on the 9th and 11th days within the gingival wounds(P＜0.05). CONCLUSIONS: Pilose antler polypeptides CNT14 has good biosafety and can promote the proliferation and migration of human oral mucosa fibroblast cells, and the expression levels of α-SMA, TGF-ß1, Smad2 and p-Smad2 were increased, promoting the regeneration of gingival tissues.

The landscape of DNA methylation in asthma: a data mining and validation.

Human asthma is caused by interactions between a range of genetic and environmental factors. However, the specific pathogenesis of asthma remains controversial. This study explored the contribution of DNA methylation to asthma using computer learning methods. Relevant datasets and information related to patients with asthma were collected from the Gene Expression Omnibus (GEO) database. A multivariate linear regression model was established. Differentially expressed genes and DNA methylation sites were identified. The results showed that the expression of 169 genes was significantly different between the two groups. Through differential analysis of methylation and differential analysis of gene expression, 44 differentially expressed genes that may be affected by DNA methylation modification were identified. The results of the multiple linear regression model showed that DNA methylation could explain 9.81% of the variation in gene expression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the differentially expressed genes, HLA-DMB, IL4, HLA-DPB1, and CD40LG, were related to the occurrence of asthma, and HLA-DMB expression was significantly reduced in allergic asthma. There was a positive correlation between cg04933135 and HLA-DMB expression, and cg04933135 was a differential site for DNA methylation. Using blood samples from asthma patients, we confirmed that HLA-DMB expression is down-regulated, which may be affected by abnormal DNA methylation. DNA methylation plays an important role in the development of asthma, and HLA-DMB which modified by abnormal DNA methylation can be regarded as a new biomarker of asthma.

Catalytic Asymmetric Transfer Hydrogenation of trans-Chalcone Derivatives Using BINOL-derived Boro-phosphates.

Chiral phosphoric-acid-catalyzed asymmetric reductions of trans-chalcones have been investigated in this work. A BINOL-derived boro-phosphate-catalyzed asymmetric transfer hydrogenation of the carbon-carbon double bond of trans-chalcone derivatives employing borane as a hydride source was realized. This methodology provides a convenient procedure to access chiral dihydrochalone derivatives in high yields and with high enantioselectivities under mild conditions.

Fluvastatin-mediated down-regulation of SATB1 affects aggressive phenotypes of human non-small-cell lung cancer cell line H292.

AIMS: Fluvastatin reduces tumor proliferation and increased apoptotic activity in various cancers. Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that reprogrammes the gene transcription profiles of tumors to promote growth and metastasis. The antitumor effect and molecular mechanisms of fluvastatin on lung cancer is poorly understood. This study aimed to investigate the antitumor effect of fluvastatin on lung cancer and its possible mechanics. MAIN METHODS: Cell viability assay was used to examine the inhibition of fluvastatin on proliferation of H292 cells. In order to investigate the antitumor mechanics, SATB1 knock-down H292 cells was constructed by lentiviral transfection. RT-PCR and Western blot were performed to examine the effects of fluvastatin on expression of SATB1 and Wnt/ß-catenin signaling components. KEY FINDINGS: Fluvastatin significantly inhibited proliferation and invasion of H292 cells in a time- and dose-dependent manner and promoted the apoptosis (p < 0.05). The expression of SATB1 was down-regulated by fluvastatin in a dose-dependent manner. The proliferation and invasion of SATB1-shRNA cells was significantly suppressed, and the apoptosis was significantly enhanced (p < 0.05). We also show that the common target genes were regulated by SATB1 and Wnt/ß-catenin pathway simultaneously. There may be a functional link between SATB1 and Wnt/ß-catenin pathway. SIGNIFICANCE: We presented a possible mechanism of statins that fluvastatin significantly suppressed the in vitro tumor progression of H292 cells possibly by down-regulation of SATB1 via Wnt/ß-catenin pathway, which provided new therapeutic possibilities for more cancers driven by hyperexpression of SATB1 and Wnt/ß-catenin pathway.

Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Hetero-triarylmethanes from Racemic Indolyl Alcohols.

The direct enantioselective 1,4- and 1,8-arylations of 7-methide-7H-indoles and 6-methide-6H-indoles, respectively, generated in situ from diarylmethanols, with electron-rich arenes as nucleophiles, has been achieved in the presence of chiral phosphoric acids (CPAs). These two remote activation protocols provide an efficient approach for the construction of diverse hetero-triarylmethanes in high yields (up to 97 %) and with excellent enantioselectivities (up to 96 %). Mechanistically inspired experiments tentatively indicate that the catalytic enantioselective 1,4-addition as well as the formal SN 1 substitution could proceed efficiently in the similar catalytic systems. Furthermore, the modification of the catalytic system and diarylmethanol structure successfully deviates the reactivity toward a remote, highly enantioselective 1,8-arylation reaction. This flexible activation mode and novel reactivity of diarylmethanols expand the synthetic potential of chiral phosphoric acids.

CD95 rs1800682 polymorphism and cervical cancer risk: evidence from a meta-analysis.

CD95 is the first death receptor identified and characterized in recent years, and it plays important roles in the molecular network regulating cell death and survival. CD95 rs1800682 polymorphism is a common genetic polymorphism identified in the CD95 gene. Many publications evaluated the association between CD95 rs1800682 polymorphism and cervical cancer risk, but the association remained inconclusive. To provide a more precise estimate on the association, a meta-analysis was carried out. The association between CD95 rs1800682 polymorphism and cervical cancer risk was assessed by calculating the pooled odds ratio (OR) with its 95% confidence intervals (95% CI). On the basis of our inclusion criteria, ten studies with a total of 5,481 individuals were included into the meta-analysis. There was obvious heterogeneity among the included studies. Meta-analysis of the ten studies suggested that there was no association between CD95 rs1800682 polymorphism and cervical cancer risk under all four genetic models (allele model: OR = 1.05, 95% CI 0.92-1.18, P = 0.478; homozygous model: OR = 1.08, 95% CI 0.83-1.41, P = 0.550; dominant model: OR = 1.12, 95% CI 0.88-1.42, P = 0.347; recessive model: OR = 1.00, 95% CI 0.76-1.31, P = 0.978). Subgroup analysis by ethnicity suggested that there was no association between CD95 rs1800682 polymorphism and cervical cancer risk in Asians, Caucasians, and Africans. Thus, the meta-analysis suggests that CD95 rs1800682 polymorphism is not associated with cervical cancer risk.

Prognostic role of hypoxic inducible factor expression in non-small cell lung cancer: a meta-analysis.

INTRODUCTION: Reported prognostic roles of hypoxic inducible factor (HIF) expression in non-small cell lung cancer (NSCLC) have varied. This meta-analysis aimed to examine the relationship between HIF expression and clinical outcome in NSCLC patients. METHODS: PubMed were used to identify relevant literature with the last report up to December 20th, 2012. After careful review, survival data were collected from eligible studies. We completed the meta-analysis using Stata statistical software (Version 11) and combined hazard ratio (HR) for overall survival (OS). Subgroup specificity, heterogeneity and publication bias were also assessed. All of the results were verified by two persons to ensure accuracy. RESULTS: Eight studies were finally stepped into this meta-analysis in which seven had available data for HIF-1α and three for HIF-2α. Combined HRs suggested that higher expression of HIF1α had a negative impact on NSCLC patient survival (HR=1.50; 95%CI =1.07-2.10; p=0.019). The expression of HIF-2α was also relative to a poorer survival (HR=2.02; 95%CI =1.47-2.77; p=0.000). No bias existed in either of the two groups. CONCLUSION: This study suggests that elevations of HIF-1α and HIF- 2α expression are both associated with poor outcome for patients with NSCLC. The data support further and high quality investigation of HIF expression for predicting poor outcome in patients with NSCLC.

Meta-analysis of the relation between vitamin D receptor gene BsmI polymorphism and susceptibility to ovarian cancer.

The role of vitamin D receptor (VDR) BsmI polymorphism in ovarian cancer development has been studied in various populations, but those results are discordant controversial and ambiguous. Thus, we performed a meta-analysis to assess the association between VDR BsmI polymorphism and susceptibility to ovarian cancer more precisely. Odds ratio (OR) and its 95% confidence interval (95% CI) were used for statistical analysis. Nine individual studies with a total 2,331 cases and 3,301 controls were included into this meta-analysis. There was no heterogeneity among those nine studies. Meta-analysis of total nine studies suggested that there was no association between VDR BsmI polymorphism and susceptibility to ovarian cancer (B vs. b, OR = 1.02, 95% CI = 0.94-1.10, P = 0.616, I(2) = 0%; BB vs. bb, OR = 1.02, 95 % CI = 0.87-1.20, P = 0.810, I(2) = 0 %; BB/Bb vs. bb, OR = 1.05, 95% CI = 0.94-1.18, P = 0.391, I(2) = 0 %; BB vs. bb/Bb, OR = 0.99, 95% CI = 0.85-1.14, P = 0.853, I(2) = 0 %). Meta-analysis of seven studies from Caucasians also showed that there was no association between VDR BsmI polymorphism and susceptibility to ovarian cancer. This meta-analysis suggests that there is no association between VDR BsmI polymorphism and susceptibility to ovarian cancer in Caucasians. Future studies from Asians or Africans are needed to further assess the above association.

Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: experimental and clinical evidence.

PURPOSE: This study aimed to examine the effect of the novel recombinant human endostatin (rh-Endo) protein on tumor vasculature, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT). METHODS: Tumor-perfusion parameters and hypoxia were monitored after rh-Endo treatment in 10 non-small cell lung-cancer (NSCLC) patients. Eight-week female C57BL/6J mice were randomized to receive rh-Endo or control (saline) once daily for 12 days when Lewis lung carcinoma (LLC) reached approximately 100-150 mm(3). On planned days, tumors were measured for cell apoptosis, microvessel density, pericytes, blood-vessel morphology, and tumor hypoxia. The tumor response under different combinations of rh-Endo and RT schedules was evaluated. RESULTS: Tumor hypoxia was significantly reduced 5 days after rh-Endo in NSCLC patients, and a similar result was found in the LLC mouse model. The anti-tumor effect was markedly enhanced when RT was administered within the remodeling period compared to any other treatment schedule. rh-Endo treatment remodeled the tumor vasculature after 5 days by reducing microvessel density and increasing pericytic coverage of the vessel endothelium. CONCLUSION: This study demonstrated decreased hypoxia in animals and patients upon rh-Endo treatment, which also enhanced the radioresponse within the vasculature-remodeling period. The optimal clinical combination of rh-Endo and RT warrants further investigation.

Insufficient screening knowledge in Chinese interns: a survey in ten leading medical schools.

OBJECTIVE: This study aimed to investigate Chinese medical interns' cancer knowledge and associated factors, focusing on cancer screening. METHODS: A questionnaire survey was conducted in ten leading Chinese medical schools from June to July in 2011. Medical interns were invited to fill the questionnaire. RESULTS: Out of the 1350 copies sent, 1135 eligible responses were returned. Around 50% of interns had positive attitude toward oncology, but the knowledge score was low, particularly in screening. The percentages of scores were 44.8% (8.95/20) for overall and only 29.6% (2.07/7) for screening. The majority of internship length in oncology department was eight to fourteen days. Screening and prevention was ranked as third most taught, following diagnosis and treatment. Multivariate analysis showed that positive attitude to oncology correlated with positive self-evaluated overall (OR = 1.76, 95% CI (1.45, 2.12)) and screening (OR = 1.62, 95% CI (1.35, 1.95)) competence, but unexpectedly predicted lower screening score (OR = 0.77, 95% CI (0.61, 0.97)). Interns with positive self-evaluated screening competence were not found to possess higher cancer screening knowledge. CONCLUSION: Current medical education in Chinese medical schools fails to equip interns with optimal cancer knowledge, particularly in screening, even in interns who hold positive view to oncology. Interns' self-evaluated competence is not proportional to their knowledge scores.