High coexpression of both EGFR and IGF1R correlates with poor patient prognosis in resected non-small-cell lung cancer

Background Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected non-small-cell lung cancer (NSCLC). Methods EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis. Results High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P =.028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P =.0004). A significant association was shown between EGFR and IGF1R protein overexpression (P <.005). Patients with high expression of both receptors had a poorer overall survival (OS) (P =.04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P =.0004 and P =.0009), with SCC having higher expression levels than ADC. Conclusion Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R. © 2014 Elsevier Inc. All rights reserved.

Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC

The PI3K/AKT/mTOR pathway regulates cell growth and proliferation and is often dysregulated in cancer due to mutation, amplification, deletion, methylation and post-translational modifications. We and others have shown that activation of this pathway in non-small cell lung cancer (NSCLC) leads to a more aggressive disease which correlates to poor prognosis for patients. A multitude of selective inhibitors are in development which target key regulators in this pathway, however the success of PI3K targeted inhibition has been hampered by a high rate of innate and acquired resistance. Response to PI3K inhibition may be improved by co-targeting potential mediators of resistance, such as related cell surface receptors or other intracellular signaling pathways which cross-talk with the PI3K pathway. Inhibition of the PI3K pathway may also overcome radioresistance, chemoresistance and immune evasion in NSCLC. The identification of appropriate patient cohorts who will benefit from PI3K co-targeted inhibition strategies will be key to the success of these inhibitors.

Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma

Early diagnosis and the ability to predict the most relevant treatment option for individuals is essential to improve clinical outcomes for non-small cell lung cancer (NSCLC) patients. Adenocarcinoma (ADC), a subtype of NSCLC, is the single biggest cancer killer and therefore an urgent need to identify minimally invasive biomarkers to enable early diagnosis. Recent studies, by ourselves and others, indicate that circulating miRNA s have potential as biomarkers. Here we applied global profiling approaches in serum from patients with ADC of the lung to explore if miRNA s have potential as diagnostic biomarkers. This study involved RNA isolation from 80 sera specimens including those from ADC patients (equal numbers of stages 1, 2, 3, and 4) and age- and gender-matched controls (n = 40 each). Six hundred and sixty-seven miRNA s were co-analyzed in these specimens using TaqMan low density arrays and qPCR validation using individual miRNA s. Overall, approximately 390 and 370 miRNA s were detected in ADC and control sera, respectively. A group of 6 miRNA s, miR-30c-1* (AU C = 0.74; P < 0.002), miR-616(AU C = 0.71; P = 0.001), miR-146b-3p (AU C = 0.82; P < 0.0001), miR-566 (AU C = 0.80; P < 0.0001), miR-550 (AU C = 0.72; P = 0.0006), and miR-939 (AU C = 0.82; P < 0.0001) was found to be present at substantially higher levels in ADC compared with control sera. Conversely, miR-339-5p and miR-656 were detected at substantially lower levels in ADC sera (co-analysis resulting in AU C = 0.6; P = 0.02). Differences in miRNA profile identified support circulating miRNA s having potential as diagnostic biomarkers for ADC. More extensive studies of ADC and control serum specimens are warranted to independently validate the potential clinical relevance of these miRNA s as minimally invasive biomarkers for ADC.

New directions for digital video creation in the classroom : spatiality, embodiment, and creativity

This column features a conversation (via email, image sharing, and Facetime) that took place over several months between two international theorists of digital filmmaking from schools in two countries—Professors Jason Ranker (Portland State University, Oregon, United States) and Kathy Mills (Queensland University of Technology, Australia). The authors discuss emerging ways of thinking about video making, sharing tips and anecdotes from classroom experience to inspire teachers to explore with adolescents the meaning potentials of digital video creation. The authors briefly discuss their previous work in this area, and then move into a discussion of how the material spaces in which students create videos profoundly shape the films' meanings and significance. The article ends with a discussion of how students can take up creative new directions, pushing the boundaries of the potentials of classroom video making and uncovering profound uses of the medium.

E-motion diaries : blogging emotional responses to online learning in higher education

Emotions are inherently social, and are central to learning, online interaction and literacy practices (Shen, Wang, & Shen, 2009). Demonstrating the dynamic sociality of literacy practice, we used e-motion diaries or web logs to explore the emotional states of pre-service high school teachers’ experiences of online learning activities. This is because the methods of communication used by university educators in online learning and writing environments play an important role in fulfilling students’ need for social interaction and inclusion (McInnerney & Roberts, 2004). Feelings of isolation and frustration are common emotions experienced by students in many online learning environments, and are associated with the success or failure of online interactions and learning (Su, et al., 2005). The purpose of the study was to answer the research question: What are the trajectories of pre-service teachers’ emotional states during online learning experiences? This is important because emotions are central to learning, and the current trend toward Massive Open Online Courses (MOOCs) needs research about students’ emotional connections in online learning environments (Kop, 2011). The project was conducted with a graduate class of 64 high school science pre-service teachers in Science Education Curriculum Studies in a large Australian university, including males and females from a variety of cultural backgrounds, aged 22-55 years. Online activities involved the students watching a series of streamed live lectures for the first 5 weeks providing a varied set of learning experiences, such as viewing science demonstrations (e.g., modeling the use of discrepant events). Each week, students provided feedback on learning by writing and posting an e-motion diary or web log about their emotional response. Students answered the question: What emotions did you experience during this learning experience? The descriptive data set included 284 online posts, with students contributing multiple entries. Linguistic appraisal theory, following Martin and White (2005), was used to regroup the 22 different discrete emotions reported by students into the six main affect groups – three positive and three negative: unhappiness/happiness, insecurity/security, and dissatisfaction/satisfaction. The findings demonstrated that the pre-service teachers’ emotional responses to the streamed lectures tended towards happiness, security, and satisfaction within the typology of affect groups – un/happiness, in/security, and dis/satisfaction. Fewer students reported that the streamed lectures triggered negative feelings of frustration, powerlessness, and inadequacy, and when this occurred, it often pertained to expectations of themselves in the forthcoming field experience in classrooms. Exceptions to this pattern of responses occurred in relation to the fifth streamed lecture presented in a non-interactive slideshow format that compressed a large amount of content. Many students responded to the content of the lecture rather than providing their emotional responses to this lecture, and one student felt “completely disengaged”. The social practice of online writing as blogs enabled the students to articulate their emotions. The findings primarily contribute new understanding about students' wide range of differing emotional states, both positive and negative, experienced in response to streamed live lectures and other learning activities in higher education external coursework. The is important because the majority of previous studies have focused on particular negative emotions, such as anxiety in test taking. The research also highlights the potentials of appraisal theory for studying human emotions in online learning and writing.

Cultural flows in an Aboriginal school : deterritorializing textual production through a socially mediated Indigenous heritage

Flows of cultural heritage in textual practices are vital to sustaining Indigenous communities. Indigenous heritage, whether passed on by oral tradition or ubiquitous social media, can be seen as a “conversation between the past and the future” (Fairclough, 2012, xv). Indigenous heritage involves appropriating memories within a cultural flow to pass on a spiritual legacy. This presentation reports ethnographic research of social media practices in a small independent Aboriginal school in Southeast Queensland, Australia that is resided over by the Yugambeh elders and an Aboriginal principal. The purpose was to rupture existing notions of white literacies in schools, and to deterritorialize the uses of digital media by dominant cultures in the public sphere. Examples of learning experiences included the following: i. Integrating Indigenous language and knowledge into media text production; ii. Using conversations with Indigenous elders and material artifacts as an entry point for storytelling; iii. Dadirri – spiritual listening in the yarning circle to develop storytelling (Ungunmerr-Baumann, 2002); and iv. Writing and publicly sharing oral histories through digital scrapbooking shared via social media. The program aligned with the Australian National Curriculum English (ACARA, 2012), which mandates the teaching of multimodal text creation. Data sources included a class set of digital scrapbooks collaboratively created in a multi-age primary classroom. The digital scrapbooks combined digitally encoded words, images of material artifacts, and digital music files. A key feature of the writing and digital design task was to retell and digitally display and archive a cultural narrative of significance to the Indigenous Australian community and its memories and material traces of the past for the future. Data analysis of the students’ digital stories involved the application of key themes of negotiated, material, and digitally mediated forms of heritage practice. It drew on Australian Indigenous research by Keddie et al. (2013) to guard against the homogenizing of culture that can arise from a focus on a static view of culture. The interpretation of findings located Indigenous appropriation of social media within broader racialized politics that enables Indigenous literacy to be understood as a dynamic, negotiated, and transgenerational flows of practice. The findings demonstrate that Indigenous children’s use of media production reflects “shifting and negotiated identities” in response to changing media environments that can function to sustain Indigenous cultural heritages (Appadurai, 1696, xv). It demonstrated how the children’s experiences of culture are layered over time, as successive generations inherit, interweave, and hear others’ cultural stories or maps. It also demonstrated how the children’s production of narratives through multimedia can provide a platform for the flow and reconstruction of performative collective memories and “lived traces of a common past” (Giaccardi, 2012). It disrupts notions of cultural reductionism and racial incommensurability that fix and homogenize Indigenous practices within and against a dominant White norm. Recommendations are provided for an approach to appropriating social media in schools that explicitly attends to the dynamic nature of Indigenous practices, negotiated through intercultural constructions and flows, and opening space for a critical anti-racist approach to multimodal text production.

Strategic targeting of the PI3K–NFκB axis in cisplatin-resistant NSCLC

Chemoresistance is a major therapeutic challenge to overcome in NSCLC, in order to improve the current survival rates of <15% at 5 years. We and others have shown increased PI3K signaling in NSCLC to be associated with a more aggressive disease, and a poorer prognosis. In this study, targeted inhibition of three strategic points of the PI3K–NFκB axis was performed with the aim of exploiting vulnerabilities in cisplatin-resistant NSCLC cells. Cisplatin-resistant cell lines were previously generated through prolonged exposure to the drug. Expression of PI3K and NFκB pathway-related genes were compared between cisplatin-resistant cells and their matched parent cells using a gene expression array, qRT-PCR, DNA sequencing, western blot, and immunofluorescence. Targeted inhibition was performed using GDC-0980, a dual PI3K–mTOR inhibitor currently in Phase II clinical trials in NSCLC, and DHMEQ, an inhibitor of NFκB translocation which has been used extensively both in vitro and in vivo. Effects of the two inhibitors were assessed by BrdU proliferation assay and multiparameter viability assay. NFKBIA was shown to be 12-fold overexpressed in cisplatin-resistant cells, with no mutations present in exons 3, 4, or 5 of the gene. Corresponding overexpression of IκBα was also observed. Treatment with DHMEQ (but not GDC-0980) led to significantly enhanced effects on viability and proliferation in cisplatin-resistant cells compared with parent cells. We conclude that NFκB inhibition represents a more promising strategy than PI3K–mTOR inhibition for treatment in the chemoresistance setting in NSCLC.

Effective responses to offenders with intellectual disabilities : generalist and specialist services working together

Despite policies of deinstitutionalisation, many people with intellectual disabilities in developed western countries continue to live in mainstream institutional settings, such as correctional facilities, rather than in the community with support from disability services. This paper reports on the life stories of 10 people with intellectual disabilities, who had been imprisoned in adult correctional facilities in Queensland. The pathways taken by these 10 people into and out of prison are marked by significant abuse, neglect, and poverty. Significant disparity and disconnection is also displayed between the policies and service approaches, particularly between the disability, mental health, and correctional systems in Queensland. Based on these findings, a framework for practice, which spans both generic and specialist services, is suggested.

Social work with marginalised people who have a mild or borderline intellectual disability : practicing gentleness and encouraging hope

People with mild or borderline intellectual disabilities are a group of people who usually do not meet the eligibility criteria for specialist disability services, yet are high users of many generalist services, such as mental health, child protection, and criminal justice systems. They may traverse many services, often entering, exiting, and returning to the same service providers with few positive results. This article explores the practice approach of the Meryton Association, a medium-sized nongovernment agency located in Brisbane, Australia. The Meryton Association provides social work support to people with mild to borderline intellectual disabilities, actively assisting this group to build relationships, resources, knowledge, and autonomy in their everyday lives. Using qualitative in-depth interviews with Meryton Association staff and secondary analysis of Meryton Association policy and practice documents, the challenges and opportunities of using this practice approach have been documented. The article proposes that specialist services are needed that use a developmental approach, stress the importance of relationship, and the need to practice gentleness and hope in social worker-client interaction.

Experiences of leaving prison for people with intellectual disability

Purpose – The support given to prisoners when they leave prison has a bearing on their success in starting a new life and on community safety. This paper aims to examine the community re-entry experiences of ten people with an intellectual disability in Queensland, Australia. Design/methodology/approach – The findings in this paper are part of a wider study on the life stories of ex-prisoners with an intellectual disability. Seven male and three female participants with intellectual disability were interviewed using a semi-structured life story method. Interviews were respectful of the communication styles of participants and involved multiple interview sessions, ranging from two to nine interviews per person. Data were analysed using narrative and thematic analysis with the assistance of NVivo 8 software. Findings – Participants found the process of leaving prison an emotional event, often clouded with both confusion about when release was to occur, and uncertainly as to what they could expect on the outside. The need for concrete information and coordinated hands-on assistance in negotiating supports in the community have significant implications for correctional and community services. Originality/value – This study captures the perspectives of people with intellectual disability on community re-entry. These perspectives are often overlooked in policy and practice developments in the field of corrections. Yet without understanding this group, the field is unable to address their particular needs.

Enhancing interdisciplinary learning with a learning management system

Interdisciplinary learning is a form of knowledge production that is increasingly being embraced as an educational approach in higher education. A role of information and communication technologies (ICT) is to enhance interdisciplinary learning. Issues surrounding the mix of interdisciplinary pedagogic methodologies and emerging digital technologies are worthy of investigation. In this paper, the authors report the findings of a study that examined student perceptions of an interdisciplinary course on information technology (IT) and visual design that utilized a learning management system. Using questionnaire instrumentation, the authors sought the perceptions of first-year university students enrolled in a newly formed interdisciplinary IT course. Results indicate that ICT-based interdisciplinary learners prefer a self-directed and collaborative instructional modality, as well as teacher presence and interventions in the online environment. The types of student participation can significantly influence how students perceive ICT-based interdisciplinary learning design.

A proteomic view into infection of greyback canegrubs (Dermolepida albohirtum) by Metarhizium anisopliae

Metarhizium anisopliae is a naturally occurring cosmopolitan fungus infecting greyback canegrubs (Dermolepida albohirtum). The main molecular factors involved in the complex interactions occurring between the greyback canegrubs and M. anisopliae (FI-1045) were investigated by comparing the proteomes of healthy canegrubs, canegrubs infected with Metarhizium and fungus only. Differentially expressed proteins from the infected canegrubs were subjected to mass spectrometry to search for pathogenicity related proteins. Immune-related proteins of canegrubs identified in this study include cytoskeletal proteins (actin), cell communication proteins, proteases and peptidases. Fungal proteins identified include metalloproteins, acyl-CoA, cyclin proteins and chorismate mutase. Comparative proteome analysis provided a view into the cellular reactions triggered in the canegrub in response to the fungal infection at the onset of biological control.