EMT and MET in carcinoma : clinical observations, regulatory pathways and new models

The articles collected here in this special edition Epithelial-Mesenchymal (EMT) and Mesenchymal-Epithelial Transitions (MET) in Cancer provide a snapshot of the very rapidly progressing cinemascope of the involvement of these transitions in carcinoma progression. Pubmed analysis of EMT and cancer shows an exponential increase in the last few years in the number of papers and reviews published under these terms (Fig. 1). The last few years have seen these articles appearing in high calibre journals including Nature, Nature Cell Biology, Cancer Cell, PNAS, JNCI, JCI, and Cell, signaling the acceptance and quality of work in this field.

Aberrant fibroblast growth factor receptor signaling in bladder and other cancers

Fibroblast growth factors (FGFs) are potent mitogens, morphogens, and inducers of angiogenesis, and FGF signaling governs the genesis of diverse tissues and organs from the earliest stages. With such fundamental embryonic and homeostatic roles, it follows that aberrant FGF signaling underlies a variety of diseases. Pathological modifications to FGF expression are known to cause salivary gland aplasia and autosomal dominant hypophosphatemic rickets, while mutations in FGF receptors (FGFRs) result in a range of skeletal dysplasias. Anomalous FGF signaling is also associated with cancer development and progression. Examples include the overexpression of FGF2 and FGF6 in prostate cancer, and FGF8 overexpression in breast and prostate cancers. Alterations in FGF signaling regulators also impact tumorigenesis, which is exemplified by the down-regulation of Sprouty 1, a negative regulator of FGF signaling, in prostate cancer. In addition, several FGFRs are mutated in human cancers (including FGFR2 in gastric cancer and FGFR3 in bladder cancer). We recently identified intriguing alterations in the FGF pathway in a novel model of bladder carcinoma that consists of a parental cell line (TSU-Pr1/T24) and two sublines with increasing metastatic potential (TSU-Pr1-B1 and TSU-Pr1-B2), which were derived successively through in vivo cycling. It was found that the increasingly metastatic sublines (TSU-Pr1-B1 and TSU-Pr1-B2) had undergone a mesenchymal to epithelial transition. FGFR2IIIc expression, which is normally expressed in mesenchymal cells, was increased in the epithelial-like TSU-Pr1-B1 and TSU-Pr1-B2 sublines and FGFR2 knock-down was associated with the reversion of cells from an epithelial to a mesenchymal phenotype. These observations suggest that modified FGF pathway signaling should be considered when studying other cancer types.

Interleukin-6 is a potent inducer of S100P, which is up-regulated in androgen-refractory and metastatic prostate cancer

Elevated circulating interleukin-6 (IL6) and up-regulated S100P in prostate cancer (PCa) specimens correlate independently with progression to androgen-independent and metastatic PCa. The cause of up-regulated S100P levels in advanced PCa remains to be determined. We investigated the possibility that IL6 is an inducer of S100P. Determination of mRNA and protein levels by real-time PCR and Western blotting revealed that IL6 is a more potent inducer of S100P than the synthetic androgen, R1881, in the LNCaP/C4-2B model of PCa progression. IL6 did not require androgen to induce S100P in these cells, which express a functional androgen receptor (AR). Like R1881, IL6 was unable to induce S100P in PC3 cells that lack a functional AR. IL6 did not strongly induce the AR-dependent genes PSA and KLK2 and, contrary to R1881, down-regulated Cyr61/CCN1, a potential marker that is down-regulated in PCa. Epidermal growth factor (EGF), which like IL6 is a non-androgen activator of the AR, did not induce S100P. The data identifies a unique gene-induction profile for IL6 and suggests that IL6 may require a functional AR for S100P induction. A link between elevated IL6 and up-regulated S100P in androgen-refractory and metastatic PCa is postulated.

BM18 : a novel androgen-dependent human prostate cancer xenograft model derived from a bone metastasis

BACKGROUND Androgen-dependent prostate cancer (PrCa) xenograft models are required to study PrCa biology in the clinically relevant in vivo environment. METHODS Human PrCa tissue from a femoral bone metastasis biopsy (BM18) was grown and passaged subcutaneously through male severe combined immune-deficient (SCID) mice. Human mitochondria (hMt), prostate specific antigen (PSA), androgen receptor (AR), cytokeratin-18 (CK-18), pan-cytokeratin, and high molecular weight-cytokeratin (HMW-CK) were assessed using immunohistochemistry (IHC). Surgical castration was performed to examine androgen dependence. Serum was collected pre- and post-castration for monitoring of PSA levels. RESULTS: BM18 stained positively for hMt, PSA, AR, CK-18, pan keratin, and negatively for HMW-CK, consistent with the staining observed in the original patient material. Androgen-deprivation induced tumor regression in 10/10 castrated male SCID mice. Serum PSA levels positively correlated with BM18 tumor size. CONCLUSIONS BM18 expresses PSA and AR, and rapidly regresses in response to androgen withdrawal. This provides a new clinically significant PrCa model for the study of androgen-dependent growth.

Two-photon fluorescence spectroscopy for identification of healthy and malignant biological tissues

Two-photon fluorescence spectroscopy has been performed on rat skeletal muscles to investigate the effect of fixation processes on the micro-environments of the endogenous fluorophors in rat skeletal muscles. The two-photon fluorescence spectra measured for different fixation periods show a differential among those samples that were fixed in water, formalin and methanol, respectively. The results imply that two-photon fluorescence spectroscopy can be a potential technique for identification of healthy and malignant biological tissues.

The Dancer as Reflective Practitioner

The inextricably intimate relationships connecting the dancer, the dance and the self indicate that the practice of dance is inherently a reflective practice of feedback looping. Professional dancers are aware of this in continuing self-critical analyses and reflections for self-improvement, striving for the ever-elusive perfection in performance. The reflective nature of learning dance is, however, less apparent to the student of dance due to the traditional master/apprentice approach to dance training. By making explicit the essentially reflective sequence of processes through which the self becomes the dancer of the dance, the locus of control is shifted towards the dance student, thereby increasing the sense of autonomy and intrinsic motivation for exploration, discovery and improvement of her or his own practice. This study documents the implementation of the 4Rs approach to reflective practice in a university dance training context. Data include reflective observations of dance lessons, and teacher and student reflections on the reflective approach taken in these lessons. Insider and outsider perspectives from students, the dance teacher and external researchers are taken to provide a nuanced understanding of the value of corporeal, visual and verbal reflection in dance for improved performance.

Leadership Enabling Effective Pedagogic Change in Higher Education

This chapter will consider pedagogic change in Higher Education from the perspective of an Assistant Dean (Teaching and Learning) and one member of their leadership team with particular focus on reflective writing in their courses. The discussion will focus on leadership for the development of teaching capability for reflective writing development and implications for quality assurance of teaching and learning across faculties of a leading comprehensive University. The authors will present and contrast the experiences and challenges of developing teaching approaches for reflective writing across the discipline of teacher education. The chapter will argue a position for the establishment of a framework of distributed leadership that supports effective pedagogical change management generally and with specific reference to reflective writing.

Teaching peer review reflective processes in accounting

A well designed peer review process in higher education subjects can lead to more confident and reflective learners who become skilled at making independent judgements of their own and others’ work; essential requirements for successful lifelong learning. The challenge for educators is to ensure their students gain these important graduate attributes within the constraints of a range of internal and external tensions currently facing higher education systems, including, respectively, the realities of large undergraduate Accounting subjects, culturally diverse and time-poor academics and students, and increased calls for public accountability of the Higher Education sector by groups such as the OECD. Innovative curriculum and assessment design and collaborative technologies have the capacity to simultaneously provide some measure of relief from these internal and external tensions and to position students as responsible partners in their own learning. This chapter reports on a two phase implementation of an online peer review process as part of the assessment in a large, under-graduate, International Accounting class. Phase One did not include explicit reflective strategies within the process, and anonymous and voluntary student views served to clearly highlight that students were ‘confused’ and ‘hesitant’ about moving away from their own ideas; often mistrusting the conflicting advice received from multiple peer reviewers. A significant number of students also felt that they did not have the skills to constructively review the work of their peers. Phase Two consequently utilised the combined power of e-Technology, peer review feedback and carefully scaffolded and supported reflective practices from Ryan and Ryan’s Teaching and Assessing Reflective Learning (TARL) model (see Chap. 2). Students found the reflective skills support workshop introduced in Phase Two to be highly useful in maximising the benefits of the peer review process, with 83 % reporting it supported them in writing peer reviews, while 90 % of the respondents reporting the workshop supported them in utilising peer and staff feedback.

The use of multimodal technologies to enhance reflective writing in teacher education

For preservice teachers new to the teaching profession, reflective practice can be a difficult process. Yet reflective writing, once mastered, has the capacity to support preservice teachers to make connections between teaching theory and professional practice, and to start to take control of their own professional learning journey. The reflective practice described in this chapter was scaffolded through a framework for writing, the use of annotated work samples and explicit teaching. This approach was enhanced through multimodal resources including written peer assessment, audio teacher feedback and a video recording of the class presentation. The video footage assisted the preservice teachers to reconcile the feedback that they received from multiple sources. This chapter describes and analyses the implementation of the PRT Pattern (Prompting Reflection using Technology). Results of this practice revealed that the multiple forms of feedback assisted the preservice teachers to analyse their performance in terms of their developing professional identity and practice.

Teaching Reflective Learning in Higher Education : A Systematic Approach Using Pedagogic Patterns

This book is about understanding the nature and application of reflection in higher education. It provides a theoretical model to guide the implementation of reflective learning and reflective practice across multiple disciplines and international contexts in higher education. The book presents research into the ways in which reflection is both considered and implemented in different ways across different professional disciplines, while maintaining a common purpose to transform and improve learning and/or practice. Readers will find this book innovative and new in three key ways. First, in its holistic theorisation of reflection within the pedagogic field of higher education; Secondly, in conceptualising reflection in different modes to achieve specific purposes in different disciplines; and finally, in providing conceptual guidance for embedding reflective learning and reflective practice in a systematic way across whole programmes, faculties or institutions in higher education. The book considers important contextual factors that influence the teaching of forms and methods of reflection. It provides a functional analysis of multiple modes of reflection, including written, oral, visual, auditory, and embodied forms. Empirical chapters analyse the application of these modes across disciplines and at different stages of a programme. The theoretical model accounts for students’ stage of development in the disciplinary field, along with progressive and cyclical levels of higher order thinking, and learning and professional practice that are expected within different disciplines and professional fields. The book provides: • A conceptual model for the application of reflection across disciplines in a variety of contexts. • Empirical examples of different modes and pedagogic patterns for reflection. • Guidance and support for embedding systemic pedagogical and curriculum change.

Introduction: Reflective and Reflexive Approaches in Higher Education : A Warrant for Lifelong Learning?

In our complex and incongruous world, where variety produces more variety, and there is no blueprint for dealing with unprecedented change, it is imperative that individuals develop reflexive approaches to life and learning. Higher education has a role to play in guiding students to be self-analysts, with the ability to examine and mediate self and context for improved outcomes. This chapter elucidates the catchphrase of lifelong learning and its enactment in higher education. Theories of reflexivity and personal epistemology are utilised to provide the conceptual tools to understand the ways in which individuals manage competing influences and deliberate about action in their learning journey. The case is made for the integral role of higher education teachers in developing students’ capacities for reflective thinking and reflexive approaches to learning as a life project.

A model for reflection in the pedagogic field of higher education

This chapter provides an introduction to the use of pedagogical patterns in capturing and sharing educational design experience. In higher education, helping students to learn to engage in productive reflection presents a complex set of challenges. Delicate balances must be found: too little structure and support for students’ reflective work can leave them floundering; too much, and some will remain dependent. Moreover, this is a dynamic teaching problem – scaffolding needs to be adjusted as students develop confidence and capability, which they will do at different rates. The model presented in this chapter embraces the three main elements that teachers can legitimately design, or help set in place, to support their students’ reflective activity: good tasks, the right tools, and appropriate divisions of labour. It delineates a complex, shifting architecture of tasks, tools and people, activities and outcomes associated with reflective learning. It shows how the designable elements of this complex mix can be described in patterns and pattern languages, which then become design resources for teachers’ own action, reflection and professional development.

Teaching and Assessing Reflective Writing in a Large Undergraduate Core Substantive Law Unit

The focus of higher education has shifted towards building students’ skills and self-awareness for future employment, in addition to developing substantive discipline knowledge. This means that there is an increasing need for embedding approaches to teaching and learning which provide a context for skills development and opportunities for students to prepare for the transition from legal education to professional practice. This chapter reports on a large (500-600 students) core undergraduate Equity law unit in an Australian University. ePortfolio has been embedded in Equity as a means of enabling students to document their reflections on their skill development in that unit. Students are taught, practice and are assessed on their teamwork and letter writing skills in the context of writing a letter of advice to a fictional client in response to a real world problem. Following submission of the team letter, students are asked to reflect on their skill development and document their reflections in ePortfolio. A scaffolded approach to teaching reflective writing is adopted using a blended model of delivery which combines face to face lectures and online resources, including an online module, facts sheets designed to guide students through the process of reflection by following the TARL model of reflection, and exemplars of reflective writing. Although students have engaged in the process of reflective writing in Equity for some years, in semester one 2011 assessment criteria were developed and the ePortfolio reflections were summatively assessed for the first time. The model of teaching and assessing reflective practice was evaluated in a range of ways by seeking feedback from students and academic staff responsible for implementing the model and asking them to reflect on their experiences. This chapter describes why skill development and reflective writing were embedded in the undergraduate law unit Equity; identify the teaching and learning approaches which were implemented to teach reflective writing to online and internal Equity students; explain the assessment processes; analyse the empirical evidence from evaluations; document the lessons learnt and discuss planned future improvements to the teaching and assessment strategies.

Sustainable Pedagogical Change for Embedding Reflective Learning Across Higher Education Programs

For pedagogical change to be sustained over time, and over the span of higher education courses, it needs to be framed widely, rather than ‘tacked on’. The framing includes curriculum reform and resource provision alongside staff pedagogical development. This is especially true for initiatives (such as reflective writing and assessment) that target broad-based, high-level skills and dispositions. For various reasons, such initiatives can easily become lost because of the discipline-specific focus of a syllabus outweighs the initiative, or because lack of resources compromises a desired approach. Course improvement in higher education contexts is typically difficult and episodic. In such circumstances, we argue that a strategic and trustworthy approach is necessary where practitioner-lead pedagogic development is fostered through trust and communication and is purposefully embedded within key dimensions of curriculum integration and resource provision. This chapter describes an approach to pedagogical change where curriculum, pedagogy and resources are simultaneously and collaboratively orchestrated to provide an effective framework for sustainable and effective change. A robust conceptual model is proposed to guide the implementation of such change.

How does the use of a reflective journal enhance students’ critical thinking about complexity?

Introduction to Youth Services is a second year Social Work and Human Services unit. In this unit a reflective writing task was introduced to assess students’ reflections on an ongoing tutorial discussion to which they contributed. The discussion was based on a fictional young person each tutorial group ‘worked with’ across eight weeks of a semester. In developing the process and the criteria for the reflective journal, the ideas raised by the Teaching and Assessing Reflective Learning (TARL) in Higher Education project (see Chap. 2) were utilised, scaffolding the work with resources and submission of a draft. The students were also invited to choose the form of reflective process they used, it could be a written journal but did not need to be. The evidence exemplified that a reflective journal is an effective tool for students to record their developing understanding regarding the concept that issues people experience are complex and compounding. Importantly, it was also a useful vehicle for students to begin to consider the impacts of their own and others’ values and beliefs on their response to the issues raised within the case discussion. The reflective journal also helped participants to consider how this learning contributes to the ongoing development of their professional practice framework.