Quantitative proteomics can be used as a screening tool for identification of differentially expressed proteins as potential biomarkers for cancers. Candidate biomarkers from such studies can subsequently be tested using other techniques for use in early detection of cancers. Here we demonstrate the use of stable isotope labeling with amino acids in cell culture (SILAC) method to compare the secreted proteins (secretome) from pancreatic cancer-derived cells with that from non-neoplastic pancreatic ductal cells. We identified 145 differentially secreted proteins (>1.5-fold change), several of which were previously reported as either up-regulated (e.g. cathepsin D, macrophage colony stimulation factor, and fibronectin receptor) or down-regulated (e.g. profilin 1 and IGFBP-7) proteins in pancreatic cancer, confirming the validity of our approach. In addition, we identified several proteins that have not been correlated previously with pancreatic cancer including perlecan (HSPG2), CD9 antigen, fibronectin receptor (integrin ␤1), and a novel cytokine designated as predicted osteoblast protein (FAM3C). The differential expression of a subset of these novel proteins was validated by Western blot analysis. In addition, overexpression of several proteins not described previously to be elevated in human pancreatic cancer (CD9, perlecan, SDF4, apoE, and fibronectin receptor) was confirmed by immunohistochemical labeling using pancreatic cancer tissue microarrays suggesting that these could be further pursued as potential biomarkers. Lastly the protein expression data from SILAC were compared with mRNA expression data obtained using

Background & Aims Over-expression of FoxM1 correlates with poor prognosis in hepatocellular carcinoma (HCC). Moreover, the Ras-signaling pathway is found to be ubiquitously activated in HCC through epigenetic silencing of the Ras-regulators. We investigated the roles of FoxM1 in Ras-driven HCC, and on HCC cells with stem-like features. Methods We employed a transgenic mouse model that expresses the oncogenic Ras in the liver. That strain was crossed with a strain that harbor floxed alleles of FoxM1 and the MxCre gene that allows conditional deletion of FoxM1. FoxM1 alleles were deleted after development of HCC, and the effects on the tumors were analyzed. Also, FoxM1-siRNA was used in human HCC cell lines to determine its role in the survival of the HCC cells with stem cell features. Results Ras-driven tumors over-express FoxM1. Deletion of FoxM1 inhibits HCC progression. There was increased accumulation of reactive oxygen species (ROS) in the FoxM1-deleted HCC cells. Moreover, FoxM1-deletion caused a disproportionate loss of the CD44+ and EpCAM+ HCC cells in the tumors. We show that FoxM1 directly activates expression of CD44 in human HCC cells. Moreover, the human HCC cells with stem cell features are addicted to FoxM1 for ROS-regulation and survival. Conclusion Our results provide genetic evidence for an essential role of FoxM1 in the progression of Ras-driven HCC. In addition, FoxM1 is required for the expression of CD44 in HCC cells. Moreover, FoxM1 plays a critical role in the survival of the HCC cells with stem cell features by regulating ROS.

Tuberculosis (TB) is a slow growing, potentially debilitating disease that has plagued humanity for centuries and has claimed numerous lives across the globe. Concerted efforts by researchers have culminated in the development of various strategies to combat this malady. This review aims to raise awareness of the rapidly increasing incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, highlighting the significant modifications that were introduced in the TB treatment regimen over the past decade. A description of the role of pathogen–host immune mechanisms together with strategies for prevention of the disease is discussed. The struggle to develop novel drug therapies has continued in an effort to reduce the treatment duration, improve patient compliance and outcomes, and circumvent TB resistance mechanisms. Herein, we give an overview of the extensive medicinal chemistry efforts made during the past decade toward the discovery of new chemotypes, which are potentially active against TB-resistant strains.

Conventional DNA ladder assay has certain shortcomings such as loss of DNA fragments during sample processing, involvement of multiple steps and requirement of expensive reagents. The present study demonstrates a rapid, easy-to-perform cost-effective method for detection of apoptotic DNA fragments with considerable improvement in the sensitivity by avoiding loss of DNA fragments. It involves a few minutes of procedure involving direct lysis of cells with dimethyl sulphoxide (DMSO), brief vortexing, addition of 2% SDS-TE buffer, and a single step of centrifugation. This cost-and time-efficient method reduces the assay time considerably and can be used for a large number of samples with excellent sensitivity.

• Imaging-based tumour response can assist in therapeutic decisions. • Lipiodol retention as carrier agent in cTACE is a tumour necrosis biomarker. • Predicting tumour necrosis with dual imaging potentially obviates immediate post-treatment MRI. • Predicting tumour necrosis would facilitate further therapeutic decisions in HCC post-cTACE. • Pre-TACE MRI and post-TACE CT predict necrosis in treated HCC.

Objectives Late contrast enhancement visualizes myocardial infarction, but the contrast to noise ratio (CNR) is low using conventional CT. The aim of this study was to determine if spectral CT can improve imaging of myocardial infarction. Materials and Methods A canine model of myocardial infarction was produced in 8 animals (90-minute occlusion, reperfusion). Later, imaging was performed after contrast injection using CT at 90kVp/150kVpSn. The following reconstructions were evaluated: Single energy 90 kVp, mixed, iodine map, multiple monoenergetic conventional and monoenergetic noise optimized reconstructions. Regions of interest were measured in infarct and remote regions to calculate contrast to noise ratio (CNR) and Bhattacharya distance (a metric of the differentiation between regions). Blinded assessment of image quality was performed. The same reconstruction methods were applied to CT scans of four patients with known infarcts. Results For animal studies, the highest CNR for infarct vs. myocardium was achieved in the lowest keV (40 keV) VMo images (CNR 4.42, IQR 3.64–5.53), which was superior to 90 kVp, mixed and iodine map (p=0.008, p=0.002, p<0.001, respectively). Compared to 90 kVp and iodine map, the 40 keV VMo reconstructions showed significantly higher histogram separation (p=0.042 and p<0.0001, respectively). The VMo reconstructions showed the highest rate of excellent quality scores. A similar pattern was seen in human studies, with CNRs for infarct maximized at the lowest keV optimized reconstruction (CNR 4.44, IQR 2.86–5.94). Conclusions Dual energy in conjunction with noise-optimized monoenergetic post-processing improves CNR of myocardial infarct delineation by approximately 20 – 25%.

Our study demonstrates that venous recanalization and TIPSS for BCS are safe and efficacious.

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