Senescence and immortality in hepatocellular carcinoma

Cataloged from PDF version of article.Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 plays a relay role between DNA damage sensing and p21(Cip1) activation. pRb arrests the cell cycle by recruiting proliferation genes to facultative heterochromatin for permanent silencing. Replicative senescence that occurs in hepatocytes in culture and in liver cirrhosis is associated with lack of telomerase activity and results in telomere shortening. Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a). Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance. Thus, senescence bypass and cellular immortality is likely to contribute significantly to HCC development. Oncogene-induced senescence in premalignant lesions and reversible immortality of cancer cells including HCC offer new potentials for tumor prevention and treatment. (C) 2008 Elsevier Ireland Ltd. All rights reserved

Pluronic polymer capped biocompatible mesoporous silica nanocarriers

A facile self-assembly method is described to prepare PEGylated silica nanocarriers using hydrophobic mesoporous silica nanoparticles and a pluronic F127 polymer. Pluronic capped nanocarriers revealed excellent dispersibility in biological media with cyto- and blood compatibilities. © 2013 The Royal Society of Chemistry

Concurrent acute pancreatitis and pericardial effusion

While pleural effusion and ascites secondary to acute pancreatitis are common, clinically relevant pericardial effusion and cardiac tamponade are observed rarely. In a study by Pezzilli et al., pleural effusion was noted in 7 of the 21 patients with acute pancreatitis whereas the authors detected pericardial effusion development in only three. The authors asserted that pleural effusion was associated with severe acute pancreatitis, while pericardial effusion and the severity of acute pancreatitis were not significantly related

P.C.N. and Arena Meet Hotel

This paper deals with the analysis of a hotel facility to determine opportunity for improvements using the Process Chain Network (P.C.N.) in combination with the Arena simulation software. The information presented is based on the authors’ personal experiences as guests at hotels, and presented in a final project assignment in the MBA Production and Operations Management course

Development of a monolithic-like precast beam-column moment connection: Experimental and analytical investigation

This study aims to develop a novel monolithic-like precast beam-column connection for reinforced concrete (RC) structures. The proposed connection system has several advantages such as rapid assembly and disassembly, reusability, and replaceability if damaged during an earthquake event. An experimental investigation was first carried out to determine the seismic performance of the proposed connections. In total, six full-scale precast and monolithic T-shape beam-column connection specimens with different reinforcement ratios, specimen dimensions and detailing were tested under displacement controlled cyclic loading, while the axial load on the column was kept constant. The cyclic behaviour, curvature distribution, failure mode, energy dissipation capacity and ductility of the specimens were obtained using the experimental outputs. Detailed non-linear finite element (FE) models were then developed using ABAQUS. It is shown that the FE models can accurately predict the overall performance of the precast connections in terms of initial stiffness, lateral load-bearing capacity and post-peak behaviour. The results indicate that, in general, the precast connections exhibited considerably higher (up to 34%) ductility and ultimate drift ratio (deformability) compared to similar monolithic connections. For the same drift ratio, monolithic connections exhibited slightly higher (on average 10%) energy dissipation capacity, while the precast connections generally dissipated higher energy at their ultimate point (post-peak lateral drift corresponding to 15% loss in lateral strength). It is demonstrated that the monolithic-like precast connections can satisfy the ACI 318-14 acceptance criteria, while they also sustain the ASCE 41-17 Collapse Prevention (CP) limits. Therefore, the proposed connection system is considered to be suitable for RC structures in seismic regions

Design of a Gd-DOTA-Phthalocyanine Conjugate Combining MRI Contrast Imaging and Photosensitization Properties as a Potential Molecular Theranostic

Cataloged from PDF version of article.The design and synthesis of a phthalocyanine - Gd-DOTA conjugate is presented to open the way to novel molecular theranostics, combining the properties of MRI contrast imaging with photodynamic therapy. The rational design of the conjugate integrates isomeric purity of the phthalocyanine core substitution, suitable biocompatibility with the use of polyoxo water-solubilizing substituents, and a convergent synthetic strategy ended by the use of click chemistry to graft the Gd-DOTA moiety to the phthalocyanine. Photophysical and photochemical properties, contrast imaging experiments and preliminary in vitro investigations proved that such a combination is relevant and lead to a new type of potential theranostic agent

IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach.</p> <p>Methods</p> <p>RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes. Paired end sequencing of 22 flash frozen tumors was performed. Sequence alignments were processed with the program ELAND, expression levels with ERANGE and then bioinformatically screened for secreted protein signatures. Serum samples from women with benign and malignant pelvic masses and serial samples from women during chemotherapy regimens were measured for IGFBP-4 by ELISA. Student's t Test, ANOVA, and ROC curves were used for statistical analysis.</p> <p>Results</p> <p>Insulin-like growth factor binding protein (IGFBP-4) was consistently present in the top 7.5% of all expressed genes in all tumor samples. We then screened serum samples to determine if increased tumor expression correlated with serum expression. In an initial discovery set of 21 samples, IGFBP-4 levels were found to be elevated in patients, including those with early stage disease and normal CA125 levels. In a larger and independent validation set (82 controls, 78 cases), IGFBP-4 levels were significantly increased (p < 5 × 10^-5). IGFBP-4 levels were ~3× greater in women with malignant pelvic masses compared to women with benign masses. ROC sensitivity was 73% at 93% specificity (AUC 0.816). In women receiving chemotherapy, average IGFBP-4 levels were below the ROC-determined threshold and lower in NED patients compared to AWD patients.</p> <p>Conclusions</p> <p>This study, the first to our knowledge to use RNA-Seq for biomarker discovery, identified IGFBP-4 as overexpressed in ovarian cancer patients. Beyond this, these studies identified two additional intriguing findings. First, IGFBP-4 can be elevated in early stage disease without elevated CA125. Second, IGFBP-4 levels are significantly elevated with malignant versus benign disease. These findings provide the rationale for future validation studies.</p

Simultaneous preconcentration of trace metals in environmental samples using amberlite XAD-2010/8-hydroxyquinoline system

A simple and sensitive system for simultaneous preconcentration of Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Pb(II) and Cd(II) at trace level by flame atomic absorption spectrometry (FAAS) is proposed. Amberlite XAD-2010 packed in a column was used as sorbent. Analyte ions were sorbed in the column as their 8-hydroxyquinoline chelates; they could then be eluted by 1 mol L -1 HNO3 in acetone. The analytical conditions including pH, amounts of 8-hydroxyquinoline, sample volume etc. on the quantitative recoveries of the analytes were investigated. The effects of the concomitants ions on the recoveries of the analytes column were also studied. The detection limits, corresponding to three times the standard deviation of the blank, were found to be in the range of 0.10-0.40 μg L-1. The accuracy of the procedure was measured by analyte determinations in certified reference materials (CRM NIES No. 7 Tea Leaves and TMDW-500 Drinking Water). The applications of the presented system were performed by the analysis of some environmental samples including water samples

Antibody mediated neutralization of myelin associated EphrinB3 accelerates CNS remyelination

This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s00401-015-1521-1Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.This work was supported by the UK MS Society Grant ref: 941/11. MRNK held a NIHR Clinical Lectureship. KAN was supported by an ERC advanced award