Expression, Tissue Distribution and Function of miR-21 in Esophageal Squamous Cell Carcinoma

Objective:MiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells.Design:MiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion.Results:MiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4.Conclusions:MiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in "activating" fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment. © 2013 Nouraee et al

Monte Carlo Approaches to Parameterized Poker Squares

The paper summarized a variety of Monte Carlo approaches employed in the top three performing entries to the Parameterized Poker Squares NSG Challenge competition. In all cases AI players benefited from real-time machine learning and various Monte Carlo game-tree search techniques

Lead isotope analyses of gold–silver ores from Roşia Montană (Romania): a first step of a metal provenance study of Roman mining activity in Alburnus Maior (Roman Dacia)

The Roşia Montană ore deposit (Apuseni Mountains, Romania) is Europe’s largest Au–Ag deposit. It also corresponds to the Roman Alburnus Maior mining site, known by historians and archaeologists due to the discovery of dozens of Roman wooden wax tablets during the underground works carried out during the 18th and 19th centuries.The present geochemical research is based on a detailed archaeological and geological study of the Roman mines at Roşia Montană, making use of archaeologically and geologically documented ore samples. The geochemical analyses allowed us to establish an accurate database for the ores exploited during Roman times at Roşia Montană (and probably before). This approach represents a contribution towards improving the accuracy of metal provenance studies of gold–silver ores during antiquity in Romania, and also at an European level, because the studied ore samples represent remnants of the original ores used by the Romans for the production of precious metals.Twenty-nine ore samples and one litharge roll have been selected, prepared and analysed by MC-ICP-MS (high-resolution measurements). A specific Roşia Montană Pb isotope signature of gold–silver ores extracted by the Roman miners was obtained. This signature is distinct when compared with other ore deposits from the Apuseni Mountains, as well as within a broader region (Maramureş ore district).A litharge roll discovered in a Roman inclined adit situated close to the surface, which attests the presence of metallurgical workshops, has also been analysed. The different lead isotope values of the litharge roll and the Roşia Montană gold–silver ores suggest that other ore sources from the South Apuseni Mountains or from elsewhere were also employed by the gold metallurgy developed at Roşia Montană during Roman times

MicroRNA history : discovery, recent applications and next frontiers

We thank the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for English language editing of the manuscript.Since 1993, when the first small non-coding RNA was identified, our knowledge about microRNAs has grown exponentially. In this review, we focus on the main progress in this field and discuss the most important findings under a historical perspective. In addition, we examine microRNAs as markers ofdisease diagnosis and prognosis, and as new therapeutic targets.M.I.A is supported by a PhD fellowship (SFRH/BD/47031/2008) from FCT (Fundação para a Ciência e Tecnologia) from Portugal. G.A.C. is supported as a Fellow at The University of Texas MD Anderson Research Trust, as a Fellow of The University of Texas System Regents Research Scholar, and by the CLL Global Research Foundation. Work in Dr. Calin’s laboratory was supported in part by NIH, by DoD, by 2009 Seena Magowitz – Pancreatic Cancer Action Network – AACR Pilot Grant and by the U.S./European Alliance for the Therapy of CLL

Zero-Offset VSP Monitoring of CO2Storage: Impedance Inversion and Wedge Modelling at the Ketzin Pilot Site

At the CO2 storage pilot site near the town of Ketzin (35 km west of Berlin, Germany) the sandstone reservoir at 630 m–650 m depth is thin and heterogeneous. The time-lapse analysis of zero-offset VSP measurements shows that CO2-induced amplitude changes can be observed on near-well corridor stacks. Further, we investigate whether CO2-induced amplitude changes in the monitoring data can be used to derive geometrical and petrophysical parameters governing the migration of CO2 within a brine saturated sandstone aquifer. 2D seismic-elastic modelling is done to test the processing workflow and to perform a wedge modelling study for estimation of the vertical expansion of the CO2 plume. When using the NRMS error as a measure for the similarity between the modelled and recorded repeat traces, the best match is achieved for a plume thickness of 6-7 m within the reservoir sandstone of 8 m thickness. With band limited impedance inversion a velocity reduction at the top of the reservoir of 30%, influenced by casing reverberations as well as CO2 injection, is found. The relation of seismic amplitude to CO2 saturated layer thickness and CO2-induced changes in P-wave velocities are important parameters for the quantification of the injected CO2 volume

MicroRNAs and metastases--the neuroblastoma link

[Excerpt] MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotides in length that regulate gene expression post-transcriptionally. These small RNAs are fundamental regulators of several cellular processes, such as differentiation, development, apoptosis, proliferation, cell cycle regulation and metabolism, through the binding to 3' untranslated regions, coding sequence or 5' untranslated regions of target messenger RNAs (mRNAs), preventing their translation or causing their degradation.1 A modest change in only one miRNA will affect multiple mRNA targets; consequently, the deregulation of miRNAs has important consequences to the cellular homeostatic stability, and aberrant miRNAs expression patterns have been described in several types of cancer.2 Recently, miRNAs have been implicated in the metastatic process of several tumors such as human breast and colorectal cancers3 and, as reported this issue of Cancer Biology & Therapy by Guo et al. in neuroblastoma.4 These are extracranial solid tumors, arising from neural crest cells, that are most common in infants and children; metastasis, the main cause of death, is present at the time of diagnosis in approximately 60% of patients. (5) [...

The Many Faces of Long Noncoding RNAs in Cancer

SIGNIFICANCE: The emerging connections between an increasing number of long noncoding RNAs (lncRNAs) and oncogenic hallmarks provide a new twist to tumor complexity. Recent Advances: In the present review, we highlight specific lncRNAs that have been studied in relation to tumorigenesis, either as participants in the neoplastic process or as markers of pathway activity or drug response. These transcripts are typically deregulated by oncogenic or tumor-suppressing signals or respond to microenvironmental conditions such as hypoxia. CRITICAL ISSUES: Among these transcripts are lncRNAs sufficiently divergent between mouse and human genomes that may contribute to biological differences between species. FUTURE DIRECTIONS: From a translational standpoint, knowledge about primate-specific lncRNAs may help explain the reason behind the failure to reproduce the results from mouse cancer models in human cell-based systems. Antioxid. Redox Signal. 29, 922-935

Computational Techniques for Analysis of Genetic Network Dynamics

In this paper we propose modeling and analysis techniques for genetic networks that provide biologists with insight into the dynamics of such systems. Central to our modeling approach is the framework of hybrid systems and our analysis tools are derived from formal analysis of such systems. Given a set of states characterizing a property of biological interest P, we present the Multi-Affine Rectangular Partition (MARP) algorithm for the construction of a set of infeasible states I that will never reach P and the Rapidly Exploring Random Forest of Trees (RRFT) algorithm for the construction of a set of feasible states F that will reach P. These techniques are scalable to high dimensions and can incorporate uncertainty (partial knowledge of kinetic parameters and state uncertainty). We apply these methods to understand the genetic interactions involved in the phenomenon of luminescence production in the marine bacterium V. fischeri