The overmethylated genes in Helicobacter pylori-infected gastric mucosa are demethylated in gastric cancers

<p>Abstract</p> <p>Background</p> <p>The transitional-CpG sites between weakly methylated genes and densely methylated retroelements are overmethylated in the gastric mucosa infected with <it>Helicobacter pylori </it>(<it>H. pylori</it>) and they are undermethylated in the gastric cancers depending on the level of loss of heterozygosity (LOH) events. This study delineated the transitional-CpG methylation patterns of CpG-island-containing and -lacking genes in view of the retroelements.</p> <p>Methods</p> <p>The transitional-CpG sites of eight CpG-island-containing genes and six CpG-island-lacking genes were semi-quantitatively examined by performing radioisotope-labelling methylation-specific PCR under stringent conditions. The level of LOH in the gastric cancers was estimated using the 40 microsatellite markers on eight cancer-associated chromosomes. Each gene was scored as overmethylated or undermethylated based on an intermediate level of transitional-CpG methylation common in the <it>H. pylori</it>-negative gastric mucosa.</p> <p>Results</p> <p>The eight CpG-island genes examined were overmethylated depending on the proximity to the nearest retroelement in the <it>H. pylori</it>-positive gastric mucosa. The six CpG-island-lacking genes were similarly methylated in the <it>H. pylori</it>-positive and -negative gastric mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island genes distant from the retroelements remained overmethylated, whereas the overmethylation of short transitional-CpG segments close to the retroelements was not significant. Both the CpG-island-containing and -lacking genes tended to be decreasingly methylated in a LOH-level-dependent manner.</p> <p>Conclusions</p> <p>The overmethylated genes under the influence of retroelement methylation in the <it>H. pylori</it>-infected stomach are demethylated in the gastric cancers influenced by LOH.</p

Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study

<p>Abstract</p> <p>Background</p> <p>Lung cancer is one of the most malignant tumors, representing a significant threat to human health. Lung cancer patients often exhibit tumor cell invasion and metastasis before diagnosis which often render current treatments ineffective. Here, we investigated the effect of staurosporine, a potent protein kinase C (PKC) inhibitor on the mobility and invasiveness of human lung adenocarcinoma A549 cells.</p> <p>Methods</p> <p>All experiments were conducted using human lung adenocarcinoma A549 cells that were either untreated or treated with 1 nmol/L, 10 nmol/L, or 100 nmol/L staurosporine. Electron microscopy analyses were performed to study ultrastructural differences between untreated A549 cells and A549 cells treated with staurosporine. The effect of staurosporine on the mobility and invasiveness of A549 was tested using Transwell chambers. Western blot analyses were performed to study the effect of staurosporine on the levels of PKC-α, integrin β1, E-cadherin, and LnR. Changes in MMP-9 and uPA levels were identified by fluorescence microscopy.</p> <p>Results</p> <p>We demonstrated that treatment of A549 cells with staurosporine caused alterations in the cell shape and morphology. Untreated cells were primarily short spindle- and triangle-shaped in contrast to staurosporine treated cells which were retracted and round-shaped. The latter showed signs of apoptosis, including vacuole fragmentation, chromatin degeneration, and a decrease in the number of microvilli at the surface of the cells. The A549 cell adhesion, mobility, and invasiveness significantly decreased with higher staurosporine concentrations. E-cadherin, integrin β1, and LnR levels changed by a factor of 1.5, 0.74, and 0.73, respectively compared to untreated cells. In addition, the levels of MMP-9 and uPA decreased in cells treated with staurosporine.</p> <p>Conclusion</p> <p>In summary, this study demonstrates that staurosporine inhibits cell adhesion, mobility, and invasion of A549 cells. The staurosporine-mediated inhibition of PKC-α, induction of E-Cad expression, and decreased integrin β1, LnR, MMP-9, and uPA levels could all possibly contribute to this biological process. These results represent a significant step forward in the ongoing effort to understand the development of lung carcinoma and to design novel strategies to inhibit metastasis of the tumor by targeting the cell-adhesion, mobility and invasion of tumor cells.</p

A review of mid-frequency vibro-acoustic modelling for high-speed train extruded aluminium panels as well as the most recent developments in hybrid modelling techniques

Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer

Glassy State Lead Tellurite Nanobelts: Synthesis and Properties

The lead tellurite nanobelts have been first synthesized in the composite molten salts (KNO3/LiNO3) method, which is cost-effective, one-step, easy to control, and performed at low-temperature and in ambient atmosphere. Scanning electron microscopy, X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectrum, energy dispersive X-ray spectroscopy and FT-IR spectrum are used to characterize the structure, morphology, and composition of the samples. The results show that the as-synthesized products are amorphous and glassy nanobelts with widths of 200–300 nm and lengths up to tens of microns and the atomic ratio of Pb:Te:O is close to 1:1.5:4. Thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC) and investigations of the corresponding structure and morphology change confirm that the nanobelts have low glass transition temperature and thermal stability. Optical diffuse reflectance spectrum indicates that the lead tellurite nanobelts have two optical gaps at ca. 3.72 eV and 4.12 eV. Photoluminescence (PL) spectrum and fluorescence imaging of the products exhibit a blue emission (round 480 nm)

High Smac/DIABLO expression is associated with early local recurrence of cervical cancer

<p>Abstract</p> <p>Background</p> <p>In a recent pilot report, we showed that Smac/DIABLO mRNA is expressed <it>de novo </it>in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients.</p> <p>Methods</p> <p>We used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10–186).</p> <p>Results</p> <p>Smac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037). Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04). Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test). No association was found between Smac/DIABLO and survival rates.</p> <p>Conclusion</p> <p>Smac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients.</p

Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.</p> <p>Methods</p> <p>This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.</p> <p>Results</p> <p>We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.</p> <p>Conclusions</p> <p>Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas.</p

REGγ is associated with multiple oncogenic pathways in human cancers

<p>Abstract</p> <p>Background</p> <p>Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Since there are limited numbers of known REGγ targets, it is not known which cancers and pathways are associated with REGγ.</p> <p>Methods</p> <p>REGγ protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REGγ in corresponding cancers were statistically analyzed. Genes highly correlated with REGγ were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues</p> <p>Results</p> <p>Here, we demonstrate overexpression of REGγ in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REGγ gene expression in the four types of cancers and identified genes significantly correlated with REGγ expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis.</p> <p>Conclusions</p> <p>This study provides us novel insights in REGγ gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGγ in multiple cancer types and implicate REGγ as a putative cancer marker.</p

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Profiling of the Tetraspanin CD151 Web and Conspiracy of CD151/Integrin β1 Complex in the Progression of Hepatocellular Carcinoma

Tetraspanin CD151 has been implicated in metastasis through forming complexes with different molecular partners. In this study, we mapped tetraspanin web proteins centered on CD151, in order to explore the role of CD151 complexes in the progression of hepatocellular carcinoma (HCC). Immunoprecipitation was used to isolate tetraspanin complexes from HCCLM3 cells using a CD151 antibody, and associated proteins were identified by mass spectrometry. The interaction of CD151 and its molecular partners, and their roles in invasiveness and metastasis of HCC cells were assayed through disruption of the CD151 network. Finally, the clinical implication of CD151 complexes in HCC patients was also examined. In this study, we identified 58 proteins, characterized the tetraspanin CD151 web, and chose integrin β1 as a main partner to further investigate. When the CD151/integrin β1 complex in HCC cells was disrupted, migration, invasiveness, secretion of matrix metalloproteinase 9, and metastasis were markedly influenced. However, both CD151 and integrin β1 expression were untouched. HCC patients with high expression of CD151/integrin β1 complex had the poorest prognosis of the whole cohort of patients. Together, our data show that CD151 acts as an important player in the progression of HCC in an integrin β1-dependent manner

Yb- and Er-doped fiber laser Q-switched with an optically uniform, broadband WS2 saturable absorber.

We demonstrate a ytterbium (Yb) and an erbium (Er)-doped fiber laser Q-switched by a solution processed, optically uniform, few-layer tungsten disulfide saturable absorber (WS2-SA). Nonlinear optical absorption of the WS2-SA in the sub-bandgap region, attributed to the edge-induced states, is characterized by 3.1% and 4.9% modulation depths with 1.38 and 3.83 MW/cm(2) saturation intensities at 1030 and 1558 nm, respectively. By integrating the optically uniform WS2-SA in the Yb- and Er-doped laser cavities, we obtain self-starting Q-switched pulses with microsecond duration and kilohertz repetition rates at 1030 and 1558 nm. Our work demonstrates broadband sub-bandgap saturable absorption of a single, solution processed WS2-SA, providing new potential efficacy for WS2 in ultrafast photonic applications.The authors thank E. J. R. Kelleher for valuable discussions. MZ acknowledges support from Beihang University, China, through a Zhuoyue Bairen Program and TH from the Royal Academy of Engineering through a fellowship (Graphlex). This work at Beihang University was supported by 973 Program (2012CB315601), NSFC (61221061/61435002) and the Fundamental Research Funds for the Central Universities.This is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/srep1748