Tissue-engineered 3D tumor angiogenesis models : potential technologies for anti-cancer drug discovery

Angiogenesis is indispensable for solid tumor expansion, and thus it has become a major target of cancer research and anti-cancer therapies. Deciphering the arcane actions of various cell populations during tumor angiogenesis requires sophisticated research models, which could capture the dynamics and complexity of the process. There is a continuous need for improvement of existing research models, which engages interdisciplinary approaches of tissue engineering with life sciences. Tireless efforts to develop a new model to study tumor angiogenesis result in innovative solutions, which bring us one step closer to decipher the dubious nature of cancer. This review aims to overview the recent developments, current limitations and future challenges in three-dimensional tissue-engineered models for the study of tumor angiogenesis and for the purpose of elucidating novel targets aimed at anti-cancer drug discovery.

Kids, counselors and troubles-telling : morality-in-action in talk on an Australian children’s helpline

This article begins with the premise that morality is an intrinsic, although often invisible, aspect of everyday social action. Drawn from a corpus of fifty audiorecorded telephone calls to Kids Helpline, an Australian helpline for children and young people, we examine one call to show how the young caller and counsellor co-construct ‘morality-in-action’. Ethnomethodological understandings and, in particular, Sacks’ (1992) description of ‘Class 2’ rules and infractions show how an adolescent caller and counsellor collaboratively assemble moral versions of the caller. In puzzling out possible motives, the caller and counsellor can be seen to be attending to the implications of different moral versions of the caller. This attribution of motives is moral work in action, with motives contingently assembled, displayed and evaluated, with such work understood as displays of moral reasoning. The counselling call makes visible the counsellor’s interactional work to support and empower the client. Analysis such as this offers counsellors ways of understanding and making visible their interactional and moral work within helpline call interactions.

Parentification: Counselling talk on a helpline for children and young people

This chapter investigates counselling interactions where young clients talk about their experiences of taking on family responsibilities normatively associated with parental roles. In research counselling literature, practices where relationships in families operate so that there is a reversal of roles, with children managing the households and caring for parents and siblings, is described as parentification. Parentification is used in the counselling literature as a clinician/researcher term, which we ‘respecify’ (Garfinkel, 1991) the tem by beginning with an investigation of young clients’ own accounts of being an adult or parent and how counsellors orient to these accounts. As well as providing understandings of how young people propose accounts of their experiences of adult-child role reversal, the chapter contributes to understanding how children and young people use the resources of counselling helplines, and how counselors can communicate effectively with children and young people.

Using conversation analysis for understanding children’s talk about traumatic events

This chapter provides a theoretical overview of literature that uses conversation analysis (CA) to explore children’s interactions related to trauma and associated mental health matters. The relatively new approach of using CA to understand trauma reveals the importance of talk in the process of recovery, and also how the participants co-construct talk about traumatic experiences. The chapter will explore literature using a CA approach to investigate children’s trauma talk with professionals as well as literature specifically discussing children’s talk about their traumatic experiences with people who are not qualified therapists or psychiatrists. We conclude by calling for more research using a CA approach for investigating children’s traumatic experiences due to the insight it provides into each child’s personal sense making of traumatic events with a range of people.

Blood in our hearts or blood on our hands? The viscosity, vitality and validity of Aboriginal 'blood talk'

Blood metaphors abound in everyday social discourse among both Aboriginal and non-Aboriginal people. However, ‘Aboriginal blood talk’, more specifically, is located within a contradictory and contested space in terms of the meanings and values that can be attributed to it by Aboriginal and non-Aboriginal people. In the colonial context, blood talk operated as a tool of oppression for Aboriginal people via blood quantum discourses, yet today, Aboriginal people draw upon notions of blood, namely bloodlines, in articulating their identities. This paper juxtaposes contemporary Aboriginal blood talk as expressed by Aboriginal people against colonial blood talk and critically examines the ongoing political and intellectual governance regarding the validity of this talk in articulating Aboriginalities.

Review: Let's talk kinship: Innovating Australian social work education, theory, research and practice through Aboriginal knowledge

Review(s) of: Let's talk kinship: Innovating Australian social work education, theory, research and practice through Aboriginal knowledge, by Christine Fejo-King, published by Christine Fejo-King Consulting, ISBN: 978-0-9922814-0-3.

‘Just choose the easy option’: Students talk about alcohol use and social influence

Previous research into young people’s drinking behaviour has studied how social practices influence their actions and how they negotiate drinking-related identities. Here, adopting the perspective of discursive psychology we examine how, for young people, social influences are bound up with issues of drinking and of identity. We conducted 19 focus groups with undergraduate students in Australia aged between 18 and 24 years. Thematic analysis of participants’ accounts for why they drink or do not drink was used to identify passages of talk that referred to social influence, paying particular attention to terms such as ‘pressure’ and ‘choice’. These passages were then analysed in fine-grained detail, using discourse analysis, to study how participants accounted for social influence. Participants treated their behaviour as accountable and produced three forms of account that: (1) minimised the choice available to them, (2) explained drinking as culture and (3) described resisting peer pressure. They also negotiated gendered social dynamics related to drinking. These forms of account allowed the participants to avoid individual responsibility for drinking or not drinking. These findings demonstrate that the effects of social influence on young people’s drinking behaviour cannot be assumed, as social influence itself becomes negotiable within local contexts of talk about drinking.

How children learn to talk and how parents can help them

From within the womb, children are tuning in to the sounds of their native language.

The effect of HLA-DR on susceptibility to rheumatoid arthritis is influenced by the associated lymphotoxin α-tumor necrosis factor haplotype

Objective. HLA-DRB1, a major genetic determinant of susceptibility to rheumatoid arthritis (RA), is located within 1,000 kb of the gene encoding tumor necrosis factor (TNF). Because certain HLA-DRB1*04 subtypes increase susceptibility to RA, investigation of the role of the TNF gene is complicated by linkage disequilibrium (LD) between TNF and DRB1 alleles. By adequately controlling for this LD, we aimed to investigate the presence of additional major histocompatibility complex (MHC) susceptibility genes. Methods. We identified 274 HLA-DRB1*04-positive cases of RA and 271 HLA-DRB1*04-positive population controls. Each subject was typed for 6 single-nucleotide polymorphisms within a 4.5-kb region encompassing TNF and lymphotoxin a (LTA). LTA-TNF haplotypes in these unrelated individuals were determined using a combination of family data and the PHASE software program. Results. Significant differences in LTA-TNF haplotype frequencies were observed between different subtypes of HLA-DRB1*04. The LTA-TNF haplotypes observed were very restricted, with only 4 haplotypes constituting 81% of all haplotypes present. Among individuals carrying DRB1*0401, the LTA-TNF 2 haplotype was significantly underrepresented in cases compared with controls (odds ratio 0.5 [95% confidence interval 0.3-0.8], P = 0.007), while in those with DRB1*0404, the opposite effect was observed (P = 0.007). Conclusion. These findings suggest that the MHC contains genetic elements outside the LTA-TNF region that modify the effect of HLA-DRB1 on susceptibility to RA.

Let’s talk about lex: Narrative analysis as both research method and teaching technique in law

Law is narration: it is narrative, narrator and the narrated. As a narrative, the law is constituted by a constellation of texts – from official sources such as statutes, treaties and cases, to private arrangements such as commercial contracts, deeds and parenting plans. All are a collection of stories: cases are narrative contests of facts and rights; statutes are recitations of the substantive and procedural bases for social, economic and political interactions; private agreements are plots for future relationships, whether personal or professional. As a narrator, law speaks in the language of modern liberalism. It describes its world in abstractions rather than in concrete experience, universal principles rather than individual subjectivity. It casts people into ‘parties’ to legal relationships; structures human interactions into ‘issues’ or ‘problems’; and tells individual stories within larger narrative arcs such as ‘the rule of law’ and ‘the interests of justice’. As the narrated, the law is a character in its own story. The scholarship of law, for example, is a type of story-telling with law as its central character. For positivists, still the dominant group in the legal genre, law is a closed system of formal rules with an “immanent rationality” and its own “structure, substantive content, procedure and tradition,” dedicated to finality of judgment. For scholars inspired by the interpretative tradition in the humanities, law is a more ambivalent character, susceptible to influences from outside its realm and masking a hidden ideological agenda under its cloak of universality and neutrality. For social scientists, law is a protagonist on a wider social stage, impacting on society, the economy and the polity is often surprising ways.

Tumor-associated mutations inO6-methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality

MGMT is the primary vehicle for cellular removal of alkyl lesions from the O-6 position of guanine and the O-4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well-characterized, but somatic variants found in tumors were, prior to this work, uncharacterized. We found that MGMT G132R, from a human esophageal tumor, and MGMT G156C, from a human colorectal cancer cell line, are unable to rescue methyltransferase-deficient Escherichia coli as well as wild type (WT) human MGMT after treatment with a methylating agent. Using pre-steady state kinetics, we biochemically characterized these variants as having a reduced rate constant. G132R binds DNA containing an O6-methylguanine lesion half as tightly as WT MGMT, while G156C has a 40-fold decrease in binding affinity for the same damaged DNA versus WT. Mammalian cells expressing either G132R or G156C are more sensitive to methylating agents than mammalian cells expressing WT MGMT. G132R is slightly resistant to O6-benzylguanine, an inhibitor of MGMT in clinical trials, while G156C is almost completely resistant to this inhibitor. The impared functionality of expressed variants G132R and G156C suggests that the presence of somatic variants of MGMT in a tumor could impact chemotherapeutic outcomes.

How talk and interaction unfold in a digitally enabled preschool classroom

The use of mobile digital devices, such as laptops and tablets, has implications for how teachers interact with young students within the institutional context of educational settings. This article examines language and participation in a digitally enabled preschool classroom as students engage with teachers and peers. Ethnomethodology, conversation analysis and membership categorization analysis are used to explicate video-recorded episodes of students (aged 3-5 years) interacting while using a laptop and a tablet. Attending to the sequential organization (when, how) and the context relevance (where) of talk and interaction, analysis shows how the intersection of interactions involving the teacher, students and digital devices, shape the ways that talk and interactions unfold. Analysis found that the teacher-student interactions were jointly arranged around a participation framework that included: 1) the teacher’s embodied action that mobilizes an accompanying action by a student, 2) allocation of turn-taking and participation while using a digital device and, 3) the affordances of the digital device in relation to the participants’ social organization. In this way, it is possible to understand not just what a digital device is or does, but the affordances of what it makes possible in constituting teachers’ and students’ social and learning relationships.

Heterogeneity of miR-10b expression in circulating tumor cells

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as € liquid biopsyto aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch ® CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients.

Circulating tumor cell detection in high-risk non-metastatic prostate cancer

Purpose The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. Method Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. Results The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. Conclusion This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.