Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer : NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be upregulated in ovarian cancer cells. In this study, we report that the expression of immunoreactive NGAL (irNGAL) in ovarian tumors changes with disease grade and that this change is reflected in the concentration of NGAL in peripheral blood. A total of 59 ovarian tissues including normal, benign, borderline malignant and grades 1, 2 and 3 malignant were analyzed using immunohistochemistry. irNGAL was not present in normal ovaries and the NGAL expression was weak to moderate in benign tissues. Both borderline and grade 1 tumors displayed the highest amount of NGAL expression with moderate to strong staining, whereas in grade 2 and 3 tumors, the extent of staining was significantly less (p < 0.01) and staining intensity was weak to moderate. Staining in all cases was confined to the epithelium. NGAL expression was analyzed by ELISA in 62 serum specimens from normal and different grades of cancer patients. Compared to control samples, the NGAL concentration was 2 and 2.6-fold higher in the serum of patients with benign tumors and cancer patients with grade 1 tumors (p < 0.05) and that result was consistent with the expression of NGAL performed by Western blot. NGAL expression was evaluated by Western blot in an immortalized normal ovarian cell line (IOSE29) as well as ovarian cancer cell lines. Moderate to strong expression of NGAL was observed in epithelial ovarian cancer cell lines SKOV3 and OVCA433 while no expression of NGAL was evident in normal IOSE29 and mesenchyme-like OVHS1, PEO.36 and HEY cell lines. NGAL expression was downregulated in ovarian cancer cell lines undergoing epithelio-mesenchymal transition (EMT) induced by epidermal growth factor (EGF). Down-regulation of NGAL expression correlated with the upregulation of vimentin expression, enhanced cell dispersion and downregulation of E-cadherin expression, some of the hallmarks of EMT. EGF-induced EMT phenotypes were inhibited in the presence of AG1478, an inhibitor of EGF receptor tyrosine kinase activity. These data indicate that NGAL may be a good marker to monitor changes of benign to premalignant and malignant ovarian tumors and that the molecule may be involved in the progression of epithelial ovarian malignancies.

The epithelial-mesenchymal transition : new insights in signaling, development, and disease

The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a de. ning structural feature of organ development. Current interest in this process, which is described as an epithelial- mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1-3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the . rst being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal-epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, . brosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and . brosis, as well as the identi. cation of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991-5995).

Cadherins in the human placenta : epithelial-mesenchymal transition (EMT) and placental development

Colonisation of the maternal uterine wall by the trophoblast involves a series of alterations in the behaviour and morphology of trophoblast cells. Villous cytotrophoblast cells change from a well-organised coherently layered phenotype to one that is extravillous, acquiring a proliferative, migratory and invasive capacity, to facilitate fetal-maternal interaction. These changes are similar to those of other developmental processes falling under the umbrella of an epithelial-mesenchymal transition (EMT). Modulation of cell adhesion and cell polarity occurs through changes in cell-cell junctional molecules, such as the cadherins. The cadherins, particularly the classical cadherins (e.g. Epithelial-(E)-cadherin), and their link to adaptors called catenins at cell-cell contacts, are important for maintaining cell attachment and the layered phenotype of the villous cytotrophoblast. In contrast, reduced expression and re-organization of cadherins from these cell junctional regions promote a loosened connection between cells, coupled with reduced apico-basal polarity. Certain non-classical cadherins play an active role in cell migration processes. In addition to the classical cadherins, two other cadherins which have been reported in placental tissues are vascular endothelial (VE) cadherin and cadherin-11. Cadherin molecules are well placed to be key regulators of trophoblast cell behaviour, analogous to their role in other developmental EMTs. This review addresses cadherin expression and function in normal and diseased human placental tissues, especially in fetal growth restriction and pre-eclampsia where trophoblast invasion is reduced.

Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44HI/CD24lO/-stem cell phenotype in human breast cancer

We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44highCD24low. Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.

Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells

PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and β-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, β-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N- and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses.

A comparative analysis of the conservative bridge transition design approaches

Differential settlement at the bridge approach between the deck and rail track on ground is often considered as a source of challenging technical and economical problem. This caused by the sudden stiffness changes between the bridge deck and the track on ground, and changes in soil stiffness of backfill and sub-grade with soil moisture content and loading history. To minimise the negative social and economic impacts due to poor performances of railway tracks at bridge transition zones, it is important, a special attention to be given at design, construction and maintenance stages. It is critically challenging to obtain an appropriate design solution for any given site condition and most of the existing conventional design approaches are unable to address the actual on-site behaviour due to their inherent assumptions of continuity and lack of clarifying of the local effects. An evaluation of existing design techniques is considered to estimate their contributions to a potential solution for bridge transition zones. This paper analyses five different approaches: the Chinese Standard, the European Standard with three different approaches, and the Australian approach. Each design approach is used to calculate the layer thicknesses, accounting critical design features such as the train speed, the axle load, the backfill subgrade condition, and the dynamic loading response. Considering correlation between track degradation and design parameters, this paper concludes that there is still a need of an optimised design approach for bridge transition zones.

An application of an extended theory of planned behaviour to understand drivers' compliance with the school zones speed limit in Australia and Malaysia

This research investigated individual and situational factors that influence driver compliance with the school zones speed limit in Australia and Malaysia. Despite all the countermeasures implemented in these two countries, driver compliance with the speed limit in school zones is still poor. The findings of the research provided support for the application of the Theory of Planned Behaviour to understand and therefore influence drivers' intention to comply with the school zones speed limit in both Australia and Malaysia. The research also revealed that mindfulness, a construct rarely used in road safety before, directly influenced Australian drivers' intention to comply, while habit influenced intention to comply in Malaysia. The research raised important theoretical and cross-cultural issues for future research and highlighted the need to increase the visibility of school zones with the use of more noticeable traffic control devices.

Directing experience : an exploration of active analysis and visual cognition theory in the training of contemporary directors

The focus of this research is the creation of a stage-directing training manual on the researcher's site at the National Institute of Dramatic Art. The directing procedures build on the work of Stanislavski's Active Analysis and findings from present-day visual cognition studies. Action research methodology and evidence-based data collection are employed to improve the efficacy of both the directing procedures and the pedagogical manual. The manual serves as a supplement to director training and a toolkit for the more experienced practitioner. The manual and research findings provide a unique and innovative contribution to the field of theatre directing.

Aspects of elementary number theory illustrated in the spreadsheet environment

Number theory has in recent decades assumed a great practical importance, due primarily to its application to cryptography. This chapter discusses how elementary concepts of number theory may be illuminated and made accessible to upper secondary school students via appropriate spreadsheet models. In such environments, students can observe patterns, gain structural insight, form and test conjectures, and solve problems. The chapter begins by reviewing literature on the use of spreadsheets in general and the use of spreadsheets in number theory in particular. Two sample applications are then discussed. The first, factoring factorials, is presented and instructions are given to construct a model in Excel 2007. The second application, the RSA cryptosystem, is included because of its importance to Science, Technology, Engineering, and Mathematics (STEM) students. Number theoretic concepts relevant to RSA are discussed, and an outline of RSA. is given, with example. The chapter ends with instructions on how to construct a simple spreadsheet illustrating RSA.

Discrete phase-locked loop systems and spreadsheets

This paper demonstrates the use of a spreadsheet in exploring non-linear difference equations that describe digital control systems used in radio engineering, communication and computer architecture. These systems, being the focus of intensive studies of mathematicians and engineers over the last 40 years, may exhibit extremely complicated behaviour interpreted in contemporary terms as transition from global asymptotic stability to chaos through period-doubling bifurcations. The authors argue that embedding advanced mathematical ideas in the technological tool enables one to introduce fundamentals of discrete control systems in tertiary curricula without learners having to deal with complex machinery that rigorous mathematical methods of investigation require. In particular, in the appropriately designed spreadsheet environment, one can effectively visualize a qualitative difference in the behviour of systems with different types of non-linear characteristic.

Hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line

In this Letter a hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line is proposed. A family of spatially varying slip lengths in the Navier slip law recovers the results of past formulations for slip in continuum theories and molecular dynamics simulations and is consistent with well-established experimental observations of complete wetting. This formulation gives a general approach for continuum hydrodynamic theories. New fluid flow behaviors are also predicted yet to be seen in experiment. © 2013 American Physical Society.

Guided ionization waves : theory and experiments

This review focuses on one of the fundamental phenomena that occur upon application of sufficiently strong electric fields to gases, namely the formation and propagation of ionization waves-streamers. The dynamics of streamers is controlled by strongly nonlinear coupling, in localized streamer tip regions, between enhanced (due to charge separation) electric field and ionization and transport of charged species in the enhanced field. Streamers appear in nature (as initial stages of sparks and lightning, as huge structures-sprites above thunderclouds), and are also found in numerous technological applications of electrical discharges. Here we discuss the fundamental physics of the guided streamer-like structures-plasma bullets which are produced in cold atmospheric-pressure plasma jets. Plasma bullets are guided ionization waves moving in a thin column of a jet of plasma forming gases (e.g.,He or Ar) expanding into ambient air. In contrast to streamers in a free (unbounded) space that propagate in a stochastic manner and often branch, guided ionization waves are repetitive and highly-reproducible and propagate along the same path-the jet axis. This property of guided streamers, in comparison with streamers in a free space, enables many advanced time-resolved experimental studies of ionization waves with nanosecond precision. In particular, experimental studies on manipulation of streamers by external electric fields and streamer interactions are critically examined. This review also introduces the basic theories and recent advances on the experimental and computational studies of guided streamers, in particular related to the propagation dynamics of ionization waves and the various parameters of relevance to plasma streamers. This knowledge is very useful to optimize the efficacy of applications of plasma streamer discharges in various fields ranging from health care and medicine to materials science and nanotechnology.

Independent learning skills, self-determination theory and psychological well-being : strategies for supporting the first year university experience

The purpose of this article is to explain why the first year in higher education experience of Australian tertiary students can be improved through the explicit teaching of independent learning skills. Becoming an independent learner has many benefits, but the focus of this piece is upon the connection between independent learning and the improvement of student psychological well-being. High psychological distress levels appear to start in the first year of university education. We argue that explicitly teaching students independent learning skills is an important curriculum-based strategy that will contribute to the significant task of addressing this issue.