Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs

The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples

'Keep telling until someone listens': understanding prevention concepts in children's picture books dealing with child sexual abuse

Children’s picture books dealing with the topic of child sexual abuse appeared in the 1980s with the aim of addressing the need for age-appropriate texts to teach sexual abuse prevention concepts and to provide support for young children who may be at risk of or have already experienced sexual abuse. Despite the apparent potential of children’s picture books to convey child sexual abuse prevention concepts, very few studies have addressed the topic of child sexual abuse in children’s literature. This article critically examines a selection of 15 picture books (published in the US, Canada and Australia) for children aged 3–8 years dealing with this theme. It makes use of an established set of evaluative criteria to conduct an audit of the books’ content and applies techniques of literary discourse analysis to explain how these picture books satisfy criteria for child sexual abuse prevention. The analysis is used as a way to understand the discourses available to readers, both adults and children, on the topic of child sexual abuse. Key themes in the books include children’s empowerment and agency, and the need for persistence and hope

Promoting Well-Being in School-Based Mentoring Through Basic Psychological Needs Support: Does It Really Count?

The main goal of this research was to assess whether satisfying basic psychological needs (BPN) in a Portuguese school-based mentoring (SBM) program improved the mentored students' well-being. One uncommon feature of this program was that the mentors were also teachers of the mentees. A two-wave experimental study design was implemented to compare the mentored ( n = 157) and non-mentored students ( n = 160). Surveys were completed twice, with a 6-month interval between time points 1 and 2. The results indicate that SBM that was associated with increased support for BPN was the most effective condition for promoting academic well-being, particularly in terms of improving the mentored students' perceptions of their school environment. However, no significant differences between the mentored and non-mentored students were detected regarding personal well-being (e.g., psychological well-being) and social well-being (e.g., peer support). These findings suggest that the balanced support of BPN was important in this particular SBM program. This support and enduring mentoring relationships can facilitate the general improvement of the mentored students' well-being