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The current study aimed to investigate the function of the Hedgehog pathway and its association with epithelial-mesenchymal transition (EMT) in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). Lung tumor tissue specimens from EGFR TKI-resistant patients, including those with brain metastases, had hyperactive Hedgehog signaling compared with those from TKI-sensitive patients. SHH stimulation promoted GLI1 activation as well as cell motility in parental PC9 cells while suppressing gefitinib-induced apoptosis in gefitinib-resistant cells. SHH also promoted EMT in parental PC9 cells via E-cadherin suppression and N-cadherin and vimentin upregulation. The knockdown of GLI1 exhibited the opposite effects. Besides, SHH induced, whereas GLI1 knockdown reversed gefitinib resistance in xenograft tumors. The Hedgehog pathway inhibitor GDC-0449 synergized with gefitinib to increase xenograft tumor sensitivity to chemotherapy and extend survival in tumor-bearing animals. These results suggest the Hedgehog pathway mediates EGFR TKI resistance and induces EMT in NSCLC, representing a potential therapeutic target to defeat TKI resistance.

Long non-coding RNAs and microRNAs (miRNAs) have been reported to participate in the progression of non-small-cell lung cancer (NSCLC). Long intergenic non-protein-coding RNA 472 (LINC00472), miR-149-3p, and miR-4270 were found to be involved in tumor activities, suggesting potential roles in NSCLC. Thus, this study aimed to examine the ability of LINC00472 to influence the progression of NSCLC with the involvement of miR-149-3p and miR-4270. Initially, differentially expressed long non-coding RNAs (lncRNAs), downstream regulatory miRNAs, and genes related to NSCLC were identified. Next, the interaction among LINC00472, miR-149-3p and miR-4270, and KLLN and the p53-signaling pathway was determined. The effect of LINC00472 on the expression of E-cadherin, N-cadherin, and Vimentin was examined through gain-of-function and loss-of-function experiments. Lastly, the effects of LINC00472 on NSCLC tumor growth were assessed in vivo. LINC00472 and KLLN were found to exhibit low levels, while miR-149-3p and miR-4270 were highly expressed in NSCLC. In addition, the overexpression of LINC00472 was observed to upregulate KLLN and activate the p53-signaling pathway, which ultimately inhibited the invasion, migration, and EMT of NSCLC cells via miR-149-3p and miR-4270, corresponding to decreased N-cadherin and Vimentin and increased E-cadherin. The overexpression of LINC00472 exerted an inhibitory effect on tumor growth in vivo. Taken together, the key evidence suggests that the overexpression of LINC00472 can downregulate miR-149-3p and miR-4270 to upregulate KLLN and activate the p53-signaling pathway, thus inhibiting the development of NSCLC. This study highlights the potential of LINC00472 as a promising therapeutic target for NSCLC treatment. Keywords: long intergenic non-protein-coding RNA 472, microRNA-149-3p, microRNA-4270, KLLN, p53-signaling pathway, non-small-cell lung cancer, invasion, migration, epithelial-mesenchymal transition

Nuclear paraspeckle assembly transcript 1 (NEAT1) has been found to be dysregulated and associated with clinical progression in various human cancers. The clinical and prognostic value of NEAT1 in nasopharyngeal carcinoma (NPC) was still controversial. The aim of our study was to provide more sufficient evidence that NEAT1 expression is correlated with overall survival in patients with NPC. NEAT1 expression was detected in NPC tissue samples, and the relationship between NEAT1 expression and clinical parameters, including prognosis, was analyzed. The meta-analysis was performed to further assess the prognostic significance of NEAT1 expression in patients with NPC. In our study, we found that the levels of NEAT1 expression were increased in NPC clinical tissue specimens, and associated with advanced M classification and clinical stages. Moreover, the Kaplan-Meier analysis suggested that the levels of NEAT1 expression were negatively associated with the overall survival of patients with NPC. Furthermore, univariate and multivariate Cox regression analyses showed that NEAT1 high-expression was an independent unfavorable prognostic factor in patients with NPC. Finally, we conducted a meta-analysis including 297 patients with NPC from the three studies, and found the pooled HR (95% confidence interval [CI]) was 1.64 (95% CI: 0.68-3.93) for the random effects model and 2.04 (95% CI: 1.42-2.95) for the fixed effect model. In conclusion, NEAT1 is a potential prognostic biomarker for NPC, but more studies are needed to further verify the prognostic value of NEAT1 in patients with NPC.

Eu3+ and Dy3+ codoped Y2O3 (Y2O3:Eu3+, Dy3+) based bifunctional nanocomposites were fabricated by solid-state route. The magnetic component of the nanocomposites is Fe or Fe3O4. The composition and microstructure of the nanocomposites were studied. The results indicate that nanocomposites are mainly consisted of Y2O3:Eu3+, Dy3+ nanorods and Fe (or Fe3O4) nanoparticles. The length and diameter of the nanorods are in the size range of 500–1500 nm and 80–150 nm, respectively. The size of Fe or Fe3O4 nanoparticles is about 20 nm. A probable formation mechanism of nanocomposites has been analyzed. The fluorescence and magnetism of nanocomposites have been evaluated based on the influences of amount of raw materials.

To explore the effect of hydrogen sulfide (HThirty male Wistar rats were divided into sham operation group (Sham group), IRI group, and HCompared with the Sham group, there was intestinal mucosa structure disorder edema and shedding villous fracture in the IRI group. Ileal pathological score in IRI group was significantly increased (4.21±0.15 vs. 0.15±0.03, P0.01), while plasma HH

To compare the efficacy and safety of etoposide combined with lobaplatin or cisplatin in the first-line treatment of extensive-stage small cell lung cancer (SCLC).A total of 98 extensive-stage SCLC patients treated at the Oncology Department from March 2015 to March 2017 were enrolled and divided into etoposide + lobaplatin group (EL group, n=49) and etoposide + cisplatin group (EP group, n=49) using a random number table. The clinical data of all patients were collected, and the short-term effective rate, changes in the levels of serum tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and neurone specific enolase (NSE) before and after chemotherapy and adverse reactions were compared between the two groups. Moreover, the patients were followed up, and the overall survival (OS) and progression-free survival (PFS) were recorded.In EL group and EP group, the level of serum NSE significantly declined after treatment compared with that before treatment, but the levels of serum CEA and CYFRA21-1 were not significantly decreased after chemotherapy compared with those before chemotherapy. The incidence rate of leukopenia, erythropenia and thrombocytopenia was 71.4%, 44.9% and 40.8%, respectively, in EL group, and 85.7%, 30.6% and 24.5%, respectively, in EP group, and the degree I-II decline was more common in both groups. The proportion of gastrointestinal reactions was 14.3% and 59.2%, respectively, in EL group and EP group, with significant difference between the two groups. During follow-up, the 1-year OS was 59.2% (29/49) and 51.9% (25/49), respectively, and the 2-year OS was 26.5% (13/49) and 20.4% (10/49), respectively, in EL group and EP group. The survival curves of were plotted using the Kaplan-Meier method and log-rank test showed no statistically significant differences in the OS and PFS between the two groups.The short-term efficacy of EL and EP regimens is equivalent in the first-line treatment of extensive-stage SCLC, both OS and PFS are similar, and the adverse reactions can be tolerated. The EL regimen produced mild gastrointestinal reactions, and is worthy of clinical popularization.

Local post-weld heat treatment (PWHT) is often used for mitigating welding-induced residual stresses in pressure vessels and piping systems. As large and ultra-large pressure vessels are increasingly used in petrochemical and power generation industries, traditional local PWHT procedures stipulated in Codes and Standards become difficult to implement for some of the ultra-large vessels due to their very large diameter and overall length. In this paper, a new method referred to as primary-secondary heating based local PWHT technique (PS-PWHT) is proposed. Both finite element residual stress modeling and experimental residual stress measurements were performed for both validating the effectiveness of the proposed technique and elucidating the underling mechanisms. The results show that the PS-PWHT method can reduce welding-induced residual stresses in a significant manner, even leading to some level of compressive residual stresses at the vessel weld region.

To examine the outcomes of concurrent versus sequential whole-brain radiotherapy (WBRT) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation. Retrospectively 105 patients with NSCLC, brain metastasis, and EGFR mutation (Affiliated Hospital of Guangdong Medical University, 01/2011 to 12/2014) were grouped as: EGFR-TKIs alone (n = 39, group A), EGFR-TKIs + concurrent radiotherapy (n = 34, group B), and radiotherapy followed by EGFR-TKIs (n = 32, group C). The intracranial objective response rates of groups A, B, and C were 66.7%, 85.3%, and 75%, respectively (P .05). EGFR-TKIs and WBRT by simultaneous application improved the short- and long-term benefits to patients with NSCLC brain metastasis carrying EGFR mutation compared to concurrent application or EGFR-TKIs alone without additional adverse events.

Geo-sequestration of CO2 in deep saline aquifers is achieved by injecting CO2 into the aquifers and displacing brine. The residual water formed during the drainage process has a strong influence on traps of residual-gas. Moreover, in the context of CO2 geological storage, the characteristics of the brine–CO2–quartz system directly impact residual trapping capacities. We conducted experiments to investigate the influence of quartz content in the rocks on the formation of residual water and how much of this residual water remains after CO2 is injected. Three sandstone core samples were all saturated with 35 g/L NaCl brine. Supercritical CO2 was injected into the samples at aquifer temperature and pressure and the displaced water and water-gas mixtures were collected and measured. The results show that the irreducible water saturation was lower with higher quartz content in the rock core. The permeability of rock cores can only influence the drainage efficiency; it does not have a decisive impact on the irreducible water saturation. Based on drainage flow rates, the process of drainage can be divided into three stages termed: Pushing Drainage, Portable Drainage and Dissolved Drainage. This terminology differs slightly from previous time-frame characterizations. Note that we have used a capillary model to interpret the mechanisms that characterize the three stages in these experiments.

Lung cancer is the leading cause for cancer death due to refractory nature to current treatment strategies, understanding the regulatory mechanism of therapy resistance of lung cancer is important for lung cancer therapy. Here, we aimed to study the role of SHCBP1 in lung cancer cisplatin resistance, we found SHCBP1 was upregulated in lung cancer tissues and cells, patients with high SHCBP1 had poor prognosis. SHC binding and spindle associated 1 (SHCBP1) overexpression promoted cisplatin induced apoptosis resistance, migration and invasion determined by apoptosis assay and transwell assay with or without Matrigel, while SHCBP1 knockdown inhibited cisplatin induced apoptosis resistance, migration and invasion. Wnt pathway promoted lung cancer progression, we found SHCBP1 activated Wnt pathway, characterized by promoting β-catenin nuclear translocation. Inhibition of Wnt pathway in SHCBP1 overexpression cells reversed the effect of SHCBP1 overexpression, confirming SHCBP1 promoted lung cancer progression through activating Wnt pathway. We also found SHCBP1 expression was positively corrected with Wnt pathway activity in lung cancer samples. In summary, we found SHCBP1 promoted cisplatin induced apoptosis resistance, migration and invasion through activating Wnt pathway, providing a potential target for lung cancer therapy.

Our previous study showed that knockdown of high-mobility group A2 (HMGA2) could suppress nasopharyngeal carcinoma (NPC) cell migration, invasion, and epithelial-mesenchymal transition (EMT) process, and HMGA2 is a direct functional target of let-7 to regulate NPC cell migration, invasion, and EMT process. However, little is known about the clinical and prognostic significance of HMGA2 protein in NPC patients. The purpose of this study is to identify the clinical and prognostic roles of HMGA2 in NPC patients. We initially analyzed the microarray data and verified mRNA and protein levels of HMGA2 in NPC tissues. Immunohistochemical staining for HMGA2 protein was performed in 116 NPC patients. The associations between HMGA2 protein expression and clinicopathologic features and its prognostic significance were analyzed. In our results, we found mRNA and protein expressions of HMGA2 were upregulated in NPC tissues and cell lines. In 116 NPC tissue samples, we observed that HMGA2 protein overexpression was associated with clinical stage, lymph node metastasis, and distant metastasis. Moreover, NPC patients with high levels of HMGA2 protein expression had shorter overall survival in comparison to patients with low levels of HMGA2 protein. In multivariate analysis, HMGA2 protein overexpression was an unfavorable prognostic factor for NPC patients. In conclusion, HMGA2 is an important biomarker to predicting NPC patient's survival time.

Matrix metalloproteinase-14 (MMP-14) has been demonstrated to play an important role in tumor progression. The aim of this study was to analyze the correlation between MMP-14 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). Immunohistochemical staining for MMP-14 protein was performed in 104 patients with NSCLC. High levels of MMP-14 protein were positively correlated with the status of clinical stage (I-II vs. III-IV; P

Aldehyde dehydrogenase 1 (ALDH1) activity has now been employed successfully as a cancer stem cells (CSCs) marker in various tumors. We wanted to investigate whether ALDH1 can be used as a putative CSCs marker and a powerful prognostic factor in nasopharyngeal carcinoma (NPC). Here, we isolated ALDH1-positive cells from human NPC cell lines (5-8F and CNE2) and found that ALDH1-positive cancer cells grew faster and had higher clone formation efficiency (0.435 ± 0.15; 0.431 ± 0.025 vs. 0.131 ± 0.007; 0.121 ± 0.126), differentiation capability and had higher migration (233.00 ± 5.29; 228.60 ± 9.34 vs. 123.20 ± 7.70 vs. 97.20 ± 6.61) than those of ALDH1-negative cancer cells in vitro. In addition, ALDH1- positive cancer cells formed significantly more tumor spheres. Our in vivo experiments showed that only 5 × 103 ALDH1-positive NPC cells were required to induce tumors. Notably, ALDH1-positive cells are enriched in the side-population (SP) cells, and stem cells-like genes OCT4, BMI1, KLF4 and SOX2 are preferentially expressed in ALDH1-positive cells. Immunohistochemical results showed that the expression of ALDH1 correlated significantly with T classification (P = 0.011), N classification (P = 0.005), M classification (P = 0.002) and clinical stage (P = 0.001). Interestingly, ALDH1 expression in the tumor correlated significantly with epithelial–mesenchymal transition (EMT) markers including vimentin expression and loss of E-cadherin (P = 0.003 and 0.008, respectively). Furthermore, multivariate analyses showed that ALDH1 expression was an independent prognostic indicator (P = 0.032). Taken together, for the first time, we demonstrate that ALDH1 could be a novel stem cells marker and a valuable predictor of poor survival NPC.

It is largely recognized that PDCD4 is frequently lost in tumors of various origins, including lung cancer, and its loss contributes to tumor progression. However, its role and molecular mechanism remain largely unexplored in non-small cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was found in NSCLC tissues compared to their corresponding paracarcinoma tissues and distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth and proliferation and cell cycle transition in vitro. Conversely, knocking down PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Akt-specific inhibitor MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4 inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential therapeutic target for NSCLC.

Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer of the renal parenchyma. MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length, which function as post‑transcriptional regulators. Recently, the downregulation of miRNA (miR)-492 was observed to be associated with ccRCC; however, the molecular mechanism by which miR492 inhibited ccRCC remained to be elucidated. In the present study, it was demonstrated that miR-492 was markedly downregulated in ccRCC tissues when compared with adjacent normal tissues, as determined by reverse transcription-quantitative poymerase chain reaction (PCR). This downregulation was predominantly due to the hypermethylation of the CpG island of the miR-492 promoter, which was detected by methylation specific PCR and bisulfite genomic sequencing PCR, and was shown to inhibit miR-492 transcription. Through the use of a DNA demethylation agent, 5-aza-2'-deoxycytidine or the histone deacetylase inhibitor 4-phenylbutyric acid, the expression level of miR-492 was significantly upregulated in ccRCC cells, which further inhibited cell proliferation and invasion, while promoting cell apoptosis and adhesion. In conclusion, the present study provided novel insights into the potential mechanisms involved in ccRCC and it is hypothesized that miR-492 may become a promising therapeutic agent in the treatment of ccRCC.

Large tumor suppressor 2 (LATS2) plays significant roles in tumorigenesis and cancer progression. This study was aimed to analyze the correlation between LATS2 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). LATS2 expression was examined in 73 NSCLC clinical specimens and 22 normal lung tissues using immunohistochemistry. Low levels of LATS2 protein were inversely associated with the T classification (P=0.001), N classification (P=0.005) and clinical stage (P=0.001) in NSCLC patients. Patients with lower LATS2 expression had a significantly shorter overall survival than patients with high LATS2 expression. Multivariate analysis suggested that low expression of LATS2 was an independent prognostic indicator (P=0.002) for the survival of patients with NSCLC. Furthermore, overexpression of LATS2 resulted in mobility inhibition in NSCLC cell lines A549 and H1299, and reduced protein level of matrix metalloproteinase-2 (MMP-2) and MMP-9. On the contrary, LATS2 siRNA treatment enhanced cell mobility and increased MMP-2 and MMP-9 protein expression level. In conclusion, low expression of LATS2 is a potential unfavorable prognostic factor and promoted cell invasion and migration in NSCLC.

Nanocrystalline Fe/Fe3C composites have been fabricated by an efficient solid-state synthesis route. In this reaction process, we choose the organic compound melamine as the carbon source and hydrothermally prepared nanocrystalline Fe/Fe3O4 composite as metal precursor. X-ray diffraction, transmission electron microscopy, high-resolution transmission electron microscopy and vibrating sample magnetometry have been used to characterize the composites. The experimental results show that changing reaction temperature, reaction time and the amount of melamine allows control over the composition of Fe/Fe3C composites, particle morphology and magnetic properties. The possible formation mechanisms of as-prepared nanostructures with different morphologies are discussed briefly. Magnetization measurements indicate that the composites display ferromagnetic properties at room temperature.

The metal–ferrite composites Fe x Co 1− x /Co y Fe 1− y Fe 2 O 4 are synthesized by using disproportion of Fe (II) and reduction of Co (II) by Fe 0 under hydrothermal condition. The size of the particles of the composites decreases as the [KOH] decreasing. The composites are measured by TEM and it can be deduced that when [KOH] = 0.1, the size of the alloy body-centered cubic (BCC) in composites is 20 ± 7 nm, the size of the Cobalt ferrite (spinel) is 170 ± 50 nm. The maximal value of the saturation magnetization (Ms) of the composite is about 100.14 emu/g, which is synthesized under Co (II)/Fe (II) = 0.05, [KOH] = 1 N, T = 150 °C and t = 3 h. The value of Hc of the composite synthesized under Co (II)/Fe (II) = 0.5, t = 3 h, T = 150 °C and [KOH] = 10.2 mol/L is about 2878.19 Oe. The Fe–Co alloy is synthesized through a reduction reaction of the composites in a flowing gaseous mixture. There is a maximal value (302.9 emu/g) of the Ms for the alloys generated at 1000 °C, which is the Co 0.412 Fe 0.588 alloy.

Nanocomposites of Fe−Co alloy and cobalt-substituted magnetite magnetic materials FexCo1−x/CoyRezFe3−y−zO4 (Re = none, La, Nd, and Gd) have been obtained successfully employing a surfactant-assisted solvothermal method. The nanocomposite features hard and soft magnetic phases juxtaposed within one discrete, anisotropic structure. Sodium oleate molecules were found effective in preventing the oxidation of the Fe−Co alloy and aggregation of the magnetic microspheres. X-ray diffraction, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy were used to characterize the structure and the morphology of the products. The result of magnetic characterization reveals that the magnetic microspheres exhibit a ferromagnetic behavior and possess high saturation magnetization and low coercivity. It is expected that these magnetic microspheres with uniform size would have potential applications such as magnetic carriers for drug targeting because of their exc...

Gd 3+ -substituted micro-octahedron composites (Fe x Co 1− x /Co y Gd z Fe 3− y − z O 4 ) in which the Fe–Co alloy has either a bcc or fcc structure and the oxide is a spinel phase were fabricated by the hydrothermal method. The X-ray diffraction (XRD) patterns indicate that the as-synthesized Gd 3+ -substituted micro-octahedron composites are well crystallized. Scanning electron microscopy (SEM) images show that the final product consists of larger numbers of micro-octahedrons with the size ranging from 1.3 to 5 μm, and the size of products are increased with increasing the concentration of KOH. The effect of the Co 2+ /Fe 2+ ratio (0⩽Co 2+ /Fe 2+ ⩽1) and substitution Fe 3+ ions by Gd 3+ ions on structure, magnetic properties of the micro-octahedrons composites were investigated, and a possible growth mechanism is suggested to explain the formation of micro-octahedrons composites. The magnetic properties of the structure show the maximal saturation magnetization (107 emu/g) and the maximal coercivity (1192 Oe) detected by a vibrating sample magnetometer.

Background Let-7a has been shown to play important roles in nasopharyngeal carcinoma (NPC) cell proliferation and apoptosis, but little is known about the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis. We aimed to investigate the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis and clarified the regulation of high mobility group A2 (HMGA2) by let-7a. Methods The expression levels of let-7a and HMGA2 were examined in NPC clinical specimens using quantitative reverse transcription-PCR (RT-qPCR). HMGA2 was confirmed as a target of let-7a through luciferase reporter assays, RT-qPCR, and Western blotting. Furthermore, the roles of let-7a and HMGA2 in regulating NPC cells biological properties including proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were analyzed with let-7a mimics and si-HMGA2 transfected cells. Results Our study demonstrated that let-7a was downregulated and inversely associated with the clinical stage, T classification and N classification, and HMGA2 was upregulated and directly associated with the clinical stage and N classification in patients with NPC. Moreover, there was an inverse correlation between let-7a expression and HMGA2 expression in NPC patient. In addition, HMGA2 was negatively regulated at the posttranscriptional level by let-7a via a binding site of HMGA2-3′UTR. In addition, synthetic let-7a mimics suppressed NPC cells migration, invasion and EMT process and knockdown of HMGA2 was consistent with the effects of let-7a in NPC cells. Conclusion Let-7a directly downregulates HMGA2 protein expression, which suppress NPC cell migration, invasion and EMT process. Let-7a could serve as a potential diagnostic marker and therapeutic target for NPC. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0462-8) contains supplementary material, which is available to authorized users.

To explore the expression of MMP2 and its correlation with the clinical features and prognosis of endometrial adenocarcinoma.We collected paraffin-embedded samples from 81 patients with endometrial adenocarcinoma aged 32 to 80 years to examine the expression of MMP2 using immunohistochemistry. The correlation of MMP2 expression with the clinical characteristics and prognosis of the patients was analyzed.MMP2 protein was expressed in the cytoplasm of the tumor cells. MMP2 over-expression was negatively correlated with tumor differentiation (P=0.015) and prognosis (P=0.041) of endometrial adenocarcinoma.MMP2 over-expression is a potential malignant biomarker in endometrial adenocarcinoma.

Background CDK4 is a protein kinase in the CDK family important for G1/S phase cell cycle progression. However, the roles and molecular mechanisms of CDK4 triggering nasopharynx carcinogenesis are still unclear. Methods Lentiviral-vector mediated shRNA was used to suppress CDK4 expression and examine its molecular mechanisms. Using immunohistochemistry, we analyzed CDK4 protein expression in clinicopathologically characterized nasopharyngeal carcinoma (NPC) cases and nasopharyngeal tissues (NPs). Survival curves were plotted by the Kaplan-Meier method and compared using the log-rank test. Results In this investigation, we knocked down CDK4 expression and observed that NPC cell growth and cell cycle progression were significantly blocked by suppressing expression of CCND1, CDK6, and E2F1 as well as elevated p21 expression. Further, we found that reduced CDK4 expression elevated the expression of let-7c, a tumor-suppressive miRNA modulated by E2F1. We found that let-7c was markedly downregulated in NPC tissues compared to NPs and suppressed cell growth and cell cycle progression by modulating p15/p16/CDK4/E2F1 pathway. Finally, CDK4 protein was observed to be overexpressed in NPC tissues and could be considered an unfavorable prognosis factor for NPC patients although its independent prognostic value did not reach statistical significance (p = 0.087). Conclusions Our results demonstrated that overexpressed CDK4 is an unfavorable prognostic factor which suppresses the expression of tumor suppressive-factor let-7c through p21/CCND1/CDK6/E2F1 signaling, and inhibits cell proliferation by p15/p16/CDK4/E2F1 feedback signaling in NPC.

The aim of the present study was to analyze the expression of DNA-binding protein inhibitor 2 (ID2) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathological features. It was found that the expression of ID2 was significantly increased in NPC cells when compared with that in NP69 cell line. Similar level of ID2 cytoplasmic expression was observed in NPC when compared with that in non-cancerous nasopharynx tissues. However, the level of ID2 in nucleus was increased in NPC when compared with that in normal nasopharynx tissues. Furthermore, the higher expression level of nuclear ID2 was significantly associated with tumor size (T classification), lymph node metastasis (N classification), and clinical stage. Patients with increased ID2 expression level had poorer overall survival rates than those with low ID2 levels. The inhibition of ID2 expression in NPC cell line SUNE1 by lentiviral-mediated short hairpin RNA could suppress cell proliferation and colony formation, but did not disrupt cell migration. Knocking down the expression of ID2 by RNA interference could down-regulate the expression of Snail, suggesting that ID2-promoted cell growth, partially attributing to the regulation of Snail activity in NPC. Our study demonstrated that over-expression of ID2 protein is an unfavorable prognostic factor which promotes cell proliferation in NPC.

BackgroundThe aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis.Methodology/principal findingsExpression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot.ResultsThe expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (PConclusionOverexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells.

Background The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement of CDK4-mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer. Methods Using immunohistochemistry analysis, we analyzed CDK4 protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclear CDK4 immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level of CDK4 and clinical features was analyzed. Furthermore, we used lentiviral-mediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression. Results The expression level of CDK4 protein was significantly increased in lung cancer tissues compared to normal tissues (P < 0.001). In addition, high levels of CDK4 protein were positively correlated with the status of pathology classification (P = 0.047), lymph node metastasis (P = 0.007), and clinical stage (P = 0.004) of lung cancer patients. Patients with higher CDK4 expression had a markedly shorter overall survival time than patients with low CDK4 expression. Multivariate analysis suggested the level of CDK4 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with lung cancer. Use of lentiviral-mediated shRNA to inhibit the expression of CDK4 in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressing CDK4 expression also significantly elevated the expression of cell cycle regulator p21 Conclusion Overexpressed CDK4 is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of p21 in lung cancer

Background Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that is characterized by poor prognosis, strong tumor invasion and a high pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). The pCR rate is a prognostic factor for TNBC. We aimed to evaluate the relationship between pCR and TNBC after NAC and originally tried to identify factors related to achieving pCR for TNBC using a meta-analysis. Methods We systematically searched the literature for pCR and breast cancer after NAC and carefully identified eligibility criteria. The association between pCR and breast cancer subtypes was estimated using Review Manager, while pCR rates for TNBC and non-TNBC were determined using Meta-Analyst. Results This analysis included a total of 9,460 cases from 27 studies. The summary odds ratio estimating the relationship between pCR and breast cancer subtypes (TNBC vs non-TNBC) was 3.02 (95% confidence interval (CI), 2.66 to 3.42). The TNBC pCR rate was 28.9% (95% CI, 27.0 to 30.8%) and the non-TNBC was 12.5% (95% CI, 11.7 to 13.4%). From subgroup analyses, we identified the factors associated with the highest pCR rates for TNBC. Conclusions TNBC has a higher pCR rate than non-TNBC. In the NAC setting, these factors of platinum-containing, more than six cycles, four kinds of drugs, 16 weeks’ treatment duration and sequential chemotherapy may contribute to increasing the pCR rate.

Carbon-encapsulated Fe-Co alloy nanoparticles (Fe-Co(C)) have been fabricated with different Co/Fe ratios by an efficient solid-state route using melamine as carbon source. The structure and morphology of Fe-Co(C) nanoparticles were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM). The XRD characterization results reveal that all products are alloys with no carbide impurity. The TEM and HRTEM observations show that the alloy nanoparticles are encapsulated in carbon shells. Additionally, the reactions involved in the syntheses are postulated. The variation of magnetic properties of Fe-Co(C) with Co/Fe has been discussed according to the room temperature VSM measurement results.