Angiogenesis as a biomarker and target in cancer chemoprevention

Angiogenesis, the formation of new blood vessels from existing vasculature, is essential to the late stages of carcinogenesis, allowing tumours to grow beyond 1-2 mm in diameter, invade surrounding tissue, and metastasise. However, more than two decades ago, angiogenesis that preceded neoplastic transformation was seen. Indeed, it can be detected in inflammatory and infectious diseases that increase the risk of developing cancer. Recent advances in fluorescence endoscopy and histological assessment suggest that, for certain cancers, the degree of new blood-vessel formation may differ between the early and late stages of carcinogenic progression. The association between angiogenesis and cancer occurrence, and ease of detection of this process in accessible tissues early in carcinogenesis, mean that angiogenesis fulfils the criteria for a biomarker of the effectiveness of chemopreventive intervention. There is also some evidence that biochemical assays of angiogenic growth factors may after similar potential as surrogate biomarkers. Many natural and synthetic chemopreventive agents in development or in clinical use inhibit new vessel formation in vivo. Validation of angiogenesis as a biomarker for the effectiveness of chemoprevention should further the advancement of some chemopreventive agents.

Hypoxia-inducible factor-1α in non small cell lung cancer: Relation to growth factor, protease and apoptosis pathways

Hypoxia-inducible factor (HIF)-1α is the regulatory subunit of HIF-1 that is stabilized under hypoxic conditions. Under different circumstances, HIF-1α may promote both tumorigenesis and apoptosis. There is conflicting data on the importance of HIF-1α as a prognostic factor. This study evaluated HIF-1α expression in 172 consecutive patients with stage I-IIIA non small cell lung cancer (NSCLC) using standard immunohistochemical techniques. The extent of HIF-1α nuclear immunostaining was determined using light microscopy and the results were analyzed using the median (5%) as a low cut-point and 60% as a high positive cut-point. Using the low cut-point, positive associations were found with epidermal growth factor receptor (EGFR; p = 0.01), matrix metalloproteinase (MMP)-9 (p = 0.003), membranous (p < 0.001) and perinuclear (p = 0.004) carbonic anhydrase (CA) IX, pS3 (p = 0.008), T-stage (p = 0.042), tumor necrosis (TN; p < 0.001) and squamous histology (p < 0.001). No significant association was found with Bcl-2 or either N- or overall TMN stage or prognosis. When the high positive cut-point was used, HIF-1α was associated with a poor prognosis (p = 0.034). In conclusion, the associations with EGFR, MMP-9, p53 and CA IX suggest that these factors may either regulate or be regulated by HIF-1α. The association with TN and squamous-type histology, which is relatively more necrotic than other NSCLC types, reflects the role of hypoxia in the regulation of HIF-1α. The prognostic data may reflect a change in the behavior of HIF-1α in increasingly hypoxic environments. © 2004 Wiley-Liss, Inc.

Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer

Purpose To evaluate carbonic anhydrase (CA) IX as a surrogate marker of hypoxia and investigate the prognostic significance of different patterns of expression in non-small-cell lung cancer (NSCLC). Methods Standard immunohistochemical techniques were used to study CA IX expression in 175 resected NSCLC tumors. CA IX expression was determined by Western blotting in A549 cell lines grown under normoxic and hypoxic conditions. Measurements from microvessels to CA IX positivity were obtained. Results CA IX immunostaining was detected in 81.8% of patients. Membranous (m) (P = .005), cytoplasmic (c) (P = .018), and stromal (P < .001) CA IX expression correlated with the extent of tumor necrosis (TN). The mean distance from vascular endothelium to the start of tumor cell positivity was 90 μm, which equates to an oxygen pressure of 5.77 mmHg. The distance to blood vessels from individual tumor cells or tumor cell clusters was greater if they expressed mCA IX than if they did not (P < .001). Hypoxic exposure of A549 cells for 16 hours enhanced CAIX expression in the nuclear and cytosolic extracts. Perinuclear (p) CA IX (P = .035) was associated with a poor prognosis. In multivariate analysis, pCA IX (P = .004), stage (P = .001), platelet count (P = .011), sex (P = .027), and TN (P = .035) were independent poor prognostic factors. Conclusion These results add weight to the contention that mCA IX is a marker of tumor cell hypoxia. The absence of CA IX staining close to microvessels suggests that these vessels are functionally active. pCA IX expression is representative of an aggressive phenotype. © 2003 by American Society of Clinical Oncology.

Keep ahead of the workforce development curve through the establishment of standardised training for rail incident investigators

The Australasian rail industry lacks a consistently accepted standard of minimal training necessary to perform rail incident investigations. Current Australasian courses do not offer the breadth of development required for a comprehensive career pathway in incident investigation (Biggs, Banks & Dovan, 2012; Short, Kains & Harris, 2010).

Contemporary challenges in e-learning

Technology is impacting on most elements of organisations today and workforce development professionals have been some of the leading proponents of embracing technologies and the benefits they offer. E-learning has emerged as at least a complementary offering to face-to-face training, and in some cases has totally replaced more traditional forms of workforce development. This chapter explores the use of learning technologies and the benefits and drawbacks of their use. In particular it focuses on further exploring the issue of a perceived lack of interaction in some e-learning offerings; a factor identified as critical to address in order to ensure effective e-learning. The chapter discusses the issues of interaction and social presence to address feelings of isolation and offers some key considerations for those considering integrating technology into workforce development.

Doing collaborative reflection in the professional experience

Despite the importance of the school-based practicum experience in teacher education programs, only limited research has investigated how supervising and pre-service teacher roles and relationships are interactively achieved in situ. Using conversation analysis, we interrogate extracts of practicum talk between supervising teachers (STs) and their pre-service teachers (PTs), revealing that asymmetrical relationships are talked into being within and through their conversations about classroom practice. We compare the different structural conversational arrangements that are employed when STs provide either positive feedback or raise issues of potential difficulty in relation to their PTs’ observed classroom activities. Analysis reveals that STs tend to make evaluative statements when providing positive feedback, in contrast to initiating a process of critical reflection when talking about the need for improvements in PTs’ pedagogic practices. We conclude by arguing the need for STs to instigate sustained critical and collaborative professional conversations with their PTs during the practicum experience, enabling them to engage in reflective practice and providing them with opportunities to extend their professional knowledge and skills, thereby potentially improving their future classroom practices.

Voltammetric, spectroscopic, and microscopic investigations of electrocrystallized forms of semiconducting AgTCNQ (TCNQ=7,7,8,8-tetracyanoquinodimethane) exhibiting different morphologies and colors

Chemically synthesized AgTCNQ exists in two forms that differ in their morphologies (needles and microcrystals) and colors (red and blue). It is now shown that both forms exhibit essentially indistinguishable X-ray diffraction, spectroscopic, and thermochemical data, implying that they are not separate phases, as implied in some literature. Electrochemical reduction of TCNQ((MeCN)) in the presence of Ag+((MeCN)) generates both red and blue AgTCNQ. On glassy carbon, platinum, or indium tin oxide electrodes and at relatively positive deposition potentials, slow growth of high aspect ratio, red needle AgTCNQ crystals occurs. After longer times and at more negative deposition potentials, blue microcrystalline AgTCNQ thin films are favored. Blue AgTCNQ is postulated to be generated via reduction of a Ag+\[(TCNQ(center dot-))(TCNQ)]((MeCN)) intermediate. At even more negative potentials, Ag-(metal) formation inhibits further growth of AgTCNQ. On a gold electrode, Ag-(metal)) deposition occurs at more positive potentials than on the other electrode materials examined. However, surface plasmon resonance data indicate (hat a small potential region is available between the stripping of Ag-(metal)) and the oxidation of TCNQ(center dot-)(MeCN) back to TCNQ(MeCN) where AgTCNQ may form. AgTCNQ in both the red and blue forms also can be prepared electrochemically on a TCNQ((s)) modified electrode in -0.1 M AgNO3(aq) where deposition of Ag(m,,,I) onto the TCNQ((s)) crystals allows a charge transfer process to occur. However, the morphology formed in this solid-solid phase transformation is more difficult to control.

Why Not the Best Schools?

Why Not the Best Schools is drawn from a major research project undertaken by Brain Caldwell and Jessica Harris involving studies of successful schools in six countries (Finland, Wales, Australia, USA, China, England). It compares a total of 30 schools and examines the conditions necessary for schools anywhere to improve and attain high standards for students.

Why not the best schools? The Australia Report

"The Australia Report is part of a set of six country reports that support Why not the best schools? It contains seven case studies of successful schools in Australia and examines the reasons for their success. Through interviews with principals, other school leaders and analysis of school reports, the reports examine how these schools achieved transformation and success by actively developing and building strength in four kinds of capital: intellectual, social, financial and spiritual ? and aligning them to their mission through outstanding governance. Why Not the Best Schools?: The Australia Report is part of a set of six country reports that support Why Not the Best Schools? by Brian Caldwell and Jessica Harris (ACER Press 2008). Why Not the Best Schools? draws on the findings of the International Project to Frame the Transformation of Schools conducted in Australia, China, England, Finland."--Libraries Australia

Breakthrough in Governance

To describe and illustrate a breakthrough in the understanding of governance in schools arising from research in seven countries, and to provide guidelines to help every school to become as successful as the best.

Conditions for Successful Reforms : Characteristics of the Organisation and Culture in Chinese Schools in a Global Context

Reforms to the basic education system in China have reflected an increasing awareness of and openness to new ideas from the global education sphere. Many of the concepts involved in the development and implementation of these reforms, including adopting holistic perspectives of student development; decentralising school governance to facilitate local decision-making to address local needs; and, an increased focus on practical, lifelong learning for all involved in schools, have been promoted in research and policies throughout the world. While working within this global context, the system of schooling in China has retained a unique character that is quite different from education in the West. Drawing on an international project on school transformation, this chapter aims to examine how five secondary schools in Chongqing, a municipality in Southwestern China, have harnessed and aligned their resources to provide effective school governance following the curriculum reforms. Furthermore, the chapter will examine the similarities and differences between the organisational structures and cultures of these schools in China and successful schools in Australia, England, Finland, Wales and the United States.