AXL Is a Key Regulator of Inherent and Chemotherapy-Induced Invasion and Predicts a Poor Clinical Outcome in Early-Stage Colon Cancer

Purpose: Despite the use of 5-fluorouracil (5-FU)–based adjuvant treatments, a large proportion of patients with high-risk stage II/III colorectal cancer will relapse. Thus, novel therapeutic strategies are needed for early-stage colorectal cancer. Residual micrometastatic disease from the primary tumor is a major cause of patient relapse.

Experimental Design: To model colorectal cancer tumor cell invasion/metastasis, we have generated invasive (KRASMT/KRASWT/+chr3/p53-null) colorectal cancer cell subpopulations. Receptor tyrosine kinase (RTK) screens were used to identify novel proteins that underpin the migratory/invasive phenotype. Migration/invasion was assessed using the XCELLigence system. Tumors from patients with early-stage colorectal cancer (N = 336) were examined for AXL expression.

Results: Invasive colorectal cancer cell subpopulations showed a transition from an epithelial-to-mesenchymal like phenotype with significant increases in migration, invasion, colony-forming ability, and an attenuation of EGF receptor (EGFR)/HER2 autocrine signaling. RTK arrays showed significant increases in AXL levels in all invasive sublines. Importantly, 5-FU treatment resulted in significantly increased migration and invasion, and targeting AXL using pharmacologic inhibition or RNA interference (RNAi) approaches suppressed basal and 5-FU–induced migration and invasion. Significantly, high AXL mRNA and protein expression were found to be associated with poor overall survival in early-stage colorectal cancer tissues.

Conclusions: We have identified AXL as a poor prognostic marker and important mediator of cell migration/invasiveness in colorectal cancer. These findings provide support for the further investigation of AXL as a novel prognostic biomarker and therapeutic target in colorectal cancer, in particular in the adjuvant disease in which EGFR/VEGF–targeted therapies have failed.

Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1

Regulation of ABCB1 (P-glycoprotein/Pgp) in AML was investigated. In a historical cohort with Pgp and transcriptional regulator expression profiling data available (n=141), FOXO1 correlated with Pgp protein expression. This was confirmed in an independent cohort (n=204). Down-regulation (siRNA) or hyperactivation (nicotinamide) of FOXO1 led to corresponding changes in Pgp. Low FOXO1 expression correlated with FLT3-ITDs (p

Queering the Family: Attitudes towards Lesbian and Gay Relationships and Families in Northern Ireland

The Northern Ireland Life andTimes (NILT) Survey has asked questions on lesbian, gay, bisexual and transgender (LGBT) issues since 1998. To date survey data have focused primarily on issues relating to prejudice, discrimination and tolerance. In 2012 a range of questions focussing more specifically on LGBT1 issues was included. This collected information on knowledge and perceptions of the LGBT population; personal prejudice; attitudes on equality issues; the visibility of LGBT people and family-related issues.

This update provides an overview of some of the information emerging from this data. It discusses attitudes towards same-sex relations and notable changes over time. Given recent political debate the primary focus of this paper is on attitudes relating to ‘queer’ marriage, family and parenting. We use the term ‘queer’ here to refer to ‘the diverse family structures formed by those with non-normative gender behaviours or sexual orientations’ (Bernstein and Reimann, 2001: 3). As previous updates have noted, there have been significant legislative and policy changes in this area (Jarman, 2010) and this continues with ongoing discussions regarding the development of a Sexual Orientation Strategy for Northern Ireland (Gray et al, 2013).

Exporting Poor Health: The Irish in England

In the twentieth century, the Irish-born population in England has typically been in worse health than both the native population and the Irish population in Ireland, a reversal of the commonly observed healthy migrant effect. Recent birth cohorts living in England and born in Ireland, however, are healthier than the English population. The substantial Irish migrant health penalty arises principally for cohorts born between 1920 and 1960. In this article, we attempt to understand the processes that generated these changing migrant health patterns for Irish migrants to England. Our results suggest a strong role for economic selection in driving the dynamics of health differences between Irish-born migrants and white English populations.

Mother's Narratives of Trauma: An exploratory study of how mothers' narrate the impact of trauma on their families

This study explored the narratives of 10 mothers whose families had been impacted by potentially traumatising events. The study was set in the context of Post-Traumatic Stress Disorder (PTSD), a relatively narrow psychiatric construct, which currently dominates much professional discourse and practice in traumatology, but references literature that provides a theoretical rationale for a broader approach. Narrative Interviewing methodology was employed and mothers of families referred to a specialist clinical service were interviewed prior to professional therapeutic intervention. The 10 mothers' narratives were analysed thematically via a rigorous process involving two independent analysts and the data organised into an evolving theoretical framework of themes and supra-themes. As hypothesised, PTSD symptomatology constituted a small proportion of the mothers' narratives (6.2%). The major components of the narratives included family and relational distress (35.7%), non-pathological individual distress (24.4%), resilience (16.7%) and a prior history of adversity (16.6%). Although exploratory in nature, the results of this study are sufficiently strong to warrant further investigation and raise tentative questions regarding the appropriateness of many existing therapeutic services for people impacted by trauma.

For vulnerable families, continued postnatal care, provided by family midwives, is associated with improved maternal care and parent–child relationship

This paper illustrates how findings from two related studies can enhance nursing and midwifery practice through the evaluation of the effectiveness of a family midwives (FMs) intervention.