Bone Morphogenetic Protein 7 Effect on Human Glioblastoma Cell Transmigration and Migration.

Glioblastoma, World Health Organization-grade IV, is the most malignant glioma type and it is still an incurable tumor due to the high level of heterogeneity and uncontrolled metastatic nature. In addition to the tumorigenicity-suppressing activity, bone morphogenetic protein 7 (BMP7) has recently been found for its invasion-promoting role in glioblastoma. However, the detailed and precise mechanism in this issue should have more elucidation. Thus, in this study, we determined the BMP7 effect on glioblastoma transmigration and migration regulations and the underlying mechanisms. Human LN18/LN229 glioblastoma cells were used in this study. Our results showed a higher BMP7/pSmad5 level in human malignant glioma tissues compared to healthy brain tissues. In addition, it was demonstrated that endogenous and exogenous BMP7 stimulation could increase the transmigration and migration capabilities of human LN18/LN229 glioblastoma cells. Moreover, this event is regulated by Smad5 and p75 neurotrophin receptor (p75NTR) signaling. Furthermore, unexpected data are that the Smad1 gene knockdown could lead to the cell death of human LN18 glioblastoma cells. Overall, the present study finds that the invasion-promoting activity of BMP7 might be an autocrine stimulation of glioblastoma and this effect could be regulated by Smad5-p75NTR signaling.

γ-secretase inhibitors, DAPT and RO4929097, promote the migration of Human Glioma Cells via Smad5-downregulated E-cadherin Expression.

Malignant gliomas are a type of central nervous system cancer with extremely high mortality rates in humans. γ-secretase has been becoming a potential target for cancer therapy, including glioma, because of the involvement of its enzymatic activity in regulating the proliferation and metastasis of cancer cells. In this study, we attempted to determine whether γ-secretase activity regulates E-cadherin to affect glioma cell migration. The human glioma cell lines, including LN18 and LN229, and the γ-secretase inhibitors, including N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) and RO4929097, were used in this study. It was shown that γ-secretase activity inhibition by DAPT and RO4929097 could promote LN18 and LN229 glioma cell migration via downregulating E-cadherin mRNA and protein expressions, but not via affecting E-cadherin protein processing. In addition, γ-secretase activity inhibition was regulated by bone morphogenetic proteins-independent Smad5 activation in glioma cells. Moreover, endogenous Smad1 in glioma cells was found to play an important role in regulating E-cadherin expression and subsequent cell migration but did not affect DAPT-stimulated effects. These results help further elucidate the molecular mechanisms of γ-secretase activity regulation involved in controlling glioma cell malignancy. Information about a potential role for Smad1/5 activity upregulation and subsequent E-cadherin downregulation during inhibition of γ-secretase activity in the development of gliomas is therefore relevant for future research.

Geometrically Consistent Stereoscopic Image Editing Using Patch-Based Synthesis.

This paper presents a patch-based synthesis framework for stereoscopic image editing. The core of the proposed method builds upon a patch-based optimization framework with two key contributions: First, we introduce a depth-dependent patch-pair similarity measure for distinguishing and better utilizing image contents with different depth structures. Second, a joint patch-pair search is proposed for properly handling the correlation between two views. The proposed method successfully overcomes two main challenges of editing stereoscopic 3D media: (1) maintaining the depth interpretation, and (2) providing controllability of the scene depth. The method offers patch-based solutions to a wide variety of stereoscopic image editing problems, including depth-guided texture synthesis, stereoscopic NPR, paint by depth, content adaptation, and 2D to 3D conversion. Several challenging cases are demonstrated to show the effectiveness of the proposed method. The results of user studies also show that the proposed method produces stereoscopic images with good stereoscopics and visual quality.

Modulation of p75 neurotrophin receptor under hypoxic conditions induces migration and invasion of C6 glioma cells.

p75 neurotrophin receptor (p75NTR) has been reported to play important roles in various cancer types. However, the exact mechanism of tumorigenesis involving p75NTR is unknown. In this study, we investigated the relationship between the expression of p75NTR in malignant glioma and the impact on tumor cell migration and invasion. p75NTR and hypoxia-inducible factor-1α (HIF-1α) expression was down-regulated by short-hairpin RNA and up-regulated with expression vectors. By immunohistochemical staining and Western blot analysis, we found that p75NTR was expressed in both human and rat malignant gliomas. Knockdown of p75NTR increased the expression of vimentin, vascular endothelial growth factor, Matrix metalloproteinase 9, and TWIST, and enhanced the invasion and migration abilities assessed by transwell assay in the C6 tumor cells. Inverse expressions of p75NTR and HIF-1α were detected in glioma cell lines under hypoxic conditions, while increased HIF-1α significantly downregulated the expression of p75NTR, suggesting a HIF-1α-p75NTR-EMT pathway that may regulate glioma cells invasion and migration. Downregulation of p75NTR increased phosphorylation of Src, focal adhesion kinase (FAK) and paxillin. Knockdown of p75NTR also dysregulated ß-catenin-mediated cell junctions, and up-regulated the expressions of fibronectin and L1CAM in the cell-cell junctions, thus suggesting that p75NTR knockdown contributed to a more aggressive migration phenotype via FAK signaling pathway. Our studies suggested that modulation of p75NTR under hypoxic condition could enhance C6 cells migration and invasion by induction of EMT, and activation of the FAK pathway. The HIF-1α-p75NTR-EMT axis may play a central role in glioma tumorigenesis.

Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of vinorelbine in lung adenocarcinoma cells.

The standard treatment regimen for patients diagnosed with non-small cell lung cancer (NSCLC) with locally advanced stage III disease is concurrent chemoradiotherapy (CCRT). This study investigated the molecular effects of vinca alkaloid vinorelbine (VNR)-based CCRT. We reviewed the records of 68 patients with stage III NSCLC: 42 patients received VNR-based CCRT, and 26 were treated with radiation alone. Human lung adenocarcinoma cells were used in this study to investigate the molecular effects of glucosylceramide synthase inhibition on VNR-based CCRT. There was response rate of 66.7% with CCRT, which was better than the response rate observed with radiation alone (30.8%; P<0.001). CCRT caused an increase in cell cycle arrest at G2/M phase accompanied by apoptosis. Oxidative c-Jun N-terminal kinase (JNK) activation was involved in the increased apoptosis levels but not the cell cycle arrest. CCRT also induced an increase in ceramide accompanied by a decrease in glucosylceramide that was positively correlated with the cytotoxic effects. Pharmacologically inhibiting glucosylceramide synthase facilitated VNR- and CCRT-induced apoptosis by promoting the JNK pathway. Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of VNR by promoting JNK-mediated apoptosis in lung adenocarcinoma cells.

Remote ischemic preconditioning reduces myocardial injury in patients undergoing coronary stent implantation.

BACKGROUND: Myocardial necrosis occurs frequently in elective percutaneous coronary intervention (PCI) and is associated with subsequent major adverse cardiovascular events (MACEs). This study assessed the protective effect of remote ischemic preconditioning (RIPC) in patients undergoing successful drug-eluting stent implantation with normal baseline troponin values. METHODS: We analyzed 205 participants with normal baseline troponin values undergoing successful coronary stent implantation. Subjects were randomized to 2 groups: The RIPC group (n = 101), whose members received RIPC (created by three 5-minute inflations of a pneumatic medical tourniquet cuff to 200 mm Hg around the upper arm, interspersed with 5-minute intervals of reperfusion) < 2 hours before the PCI procedure, and the control group (n = 104). RESULTS: The primary outcomes were high sensitive cardiac troponin I (hscTnI) levels and incidence of myocardial infarction (MI 4a, defined as hscTnI > 0.20 ng/mL) at 16 hours after the PCI procedure. The median hscTnI at 16 hours after PCI was lower in the RIPC group compared with the unpreconditioned, control group (0.11 vs 0.21 ng/mL; P < 0.01). The incidence of MI 4a was lower in the RIPC group compared with the control group (39% vs 54%, P < 0.05). Index of renal function showed no difference between the 2 groups at 16 hours after PCI (P > 0.05). CONCLUSION: RIPC reduced post-PCI TnI release and incidence of MI 4a in patients undergoing elective coronary stent implantation.

Ambiguity-free edge-bundling for interactive graph visualization.

Graph visualization has been widely used to understand and present both global structural and local adjacency information in relational data sets (e.g., transportation networks, citation networks, or social networks). Graphs with dense edges, however, are difficult to visualize because fast layout and good clarity are not always easily achieved. When the number of edges is large, edge bundling can be used to improve the clarity, but in many cases, the edges could be still too cluttered to permit correct interpretation of the relations between nodes. In this paper, we present an ambiguity-free edge-bundling method especially for improving local detailed view of a complex graph. Our method makes more efficient use of display space and supports detail-on-demand viewing through an interactive interface. We demonstrate the effectiveness of our method with public coauthorship network data.