Role of CD56 in Normal Kidney Development and Wilms Tumorigenesis

The cell-surface glycoprotein CD56 has three major isoforms that play important roles in cell adhesion and signaling, which may promote cell proliferation, differentiation, survival, or migration. It is an important molecule in normal kidney development and acts as a key marker in Wilms tumor stem and progenitor cells. Here, we review the structural and genetic features of the CD56 glycoprotein, and summarize its roles in the normal versus diseased metanephric blastema. We discuss areas of CD56-related research that may complement or improve existing Wilms tumor treatment strategies, including the antibody-drug conjugate lorvotuzumab mertansine that binds to CD56

Bilateral Wilms tumour: a review of clinical and molecular features

Wilms tumour (WT) is the most common paediatric kidney cancer and affects approximately one in 10 000 children. The tumour is associated with undifferentiated embryonic lesions called nephrogenic rests (NRs) or, when diffuse, nephroblastomatosis. WT or NRs can occur in both kidneys, termed bilateral disease, found in only 5–8% of cases. Management of bilateral WT presents a major clinical challenge in terms of maximising survival, preserving renal function and understanding underlying genetic risk. In this review, we compile clinical data from 545 published cases of bilateral WT and discuss recent progress in understanding the molecular basis of bilateral WT and its associated precursor NRs in the context of the latest radiological, surgical and epidemiological features

A Survey of Therapeutic Radiographers’ Knowledge, Practices, and Barriers in Delivering Health Behaviour Advice to Cancer Patients

Therapeutic radiographers (TRs) are well-placed to deliver advice to cancer patients; however, limited research exists on their practices in providing advice on healthy lifestyle behaviours. Through an online survey, this study aimed to explore TRs’ current practices, barriers, and facilitators around delivering healthy behaviour advice to cancer patients. An online survey was sent to 72 radiotherapy departments in the UK and 583 TRs responded to the survey. Findings showed that levels of enquiry and provision of advice on healthy behaviours were low, with less than 25% advising patients on physical activity, healthy eating, weight management, smoking cessation, and reducing alcohol intake as standard practice. Lack of knowledge, resources, and training were identified as barriers, in addition to perceived lack of patient interest and lack of time. TRs reported a strong desire to undergo training to enable them to deliver health behaviour advice to patients, with an identified preference for online training. Cancer patients look to healthcare professionals for advice on health behaviours, and TRs are well-placed to deliver this advice. The findings of this study provide insight into the areas that need addressing to enable TRs to support positive health behaviours among cancer patients

Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens

PURPOSE: Selection of the most appropriate chemotherapy dosing regimens for neonates treated within the first weeks of life represents a significant clinical dilemma. Due to a lack of information relating to the clinical pharmacology of anticancer drugs in these challenging patients, current dosing guidelines are based on limited scientific rationale. In the current study, we investigate the utilisation of therapeutic drug monitoring approaches in neonates with localised hepatoblastoma, Wilms' tumour and stage 4S neuroblastoma, being treated with widely used anticancer drugs. METHODS: Plasma concentrations of cisplatin, vincristine, etoposide and carboplatin were quantified in two neonates being treated within the first 3 weeks of life and in a 32-week preterm infant treated at a gestational age of 40 weeks. Therapeutic drug monitoring was carried out where appropriate, based on the pharmacokinetic data obtained in conjunction with clinical response and toxicity. RESULTS: Treatment of a child aged 2 weeks with a recommended cisplatin dose reduction for weight to 1.8 mg/kg resulted in achievement of unbound cisplatin plasma concentrations of 0.01-0.08 µg/mL, markedly lower than exposures previously reported in infants and older children. A dose increase to 2.7 mg/kg was implemented, leading to the achievement of levels more in-line with those previously reported. This increased dose level was well tolerated over six courses of treatment, resulting in a good response to cisplatin monotherapy and the patient remains in remission at 3.5 years. In contrast, a 50 % vincristine dose reduction for weight in a 3-week-old neonate resulted in plasma concentrations comparable to levels observed in older children, leading to successful treatment and continued remission at 2 years. In a third patient, etoposide and carboplatin clearance values normalised to body weight were comparable to those reported in older children, resulting in comparatively lower exposures following reduced dosing. CONCLUSIONS: The current report provides unique data on the pharmacokinetics of several widely used anticancer drugs in neonates treated within the first few weeks of life. The provision of these data acts as a useful reference point to support future dosing decisions to be made by clinicians in the treatment of these challenging patients

Early advice on managing children with cancer during the COVID-19 pandemic and a call for sharing experiences

We are living very difficult times. The pandemic caused by SARS‐CoV‐2 (COVID‐19) is rapidly affecting the delivery of care for children with cancer around the world. We have written this commentary to facilitate the dissemination of helpful information and useful links, and to place in perspective what we do and do not know about the COVID‐19 pandemic and its impact in the practice of paediatric oncology. Generally speaking, the impact that this virus may have on the paediatric population, and the management of children with cancer, remains unclear and poorly documented. The next two sections outline what has been published or communicated via academic websites, both in children and adults with cancer

Educational attainment trajectories among children and adolescents with depression, and the role of sociodemographic characteristics: longitudinal data-linkage study

Background Depression is associated with lower educational attainment, but there has been little investigation of long-term educational trajectories in large cohorts with diagnosed depression. Aims: To describe the educational attainment trajectories of children with a depression diagnosis in secondary care, and to investigate whether these trajectories vary by sociodemographic characteristics. / Method: We identified new referrals to South London and Maudsley's NHS Foundation Trust between 2007 and 2013 who received a depression diagnosis at under 18 years old. Linking their health records to the National Pupil Database, we standardised their performance on three assessments (typically undertaken at ages 6–7 years (school Year 2), 10–11 (Year 6) and 15–16 (Year 11)) relative to the local reference population in each academic year. We used mixed models for repeated measures to estimate attainment trajectories. / Results: In our sample of 1492 children, the median age at depression diagnosis was 15 years (interquartile range = 14–16). Their attainment showed a decline between school Years 6 and 11. Attainment was consistently lower among males and those eligible for free school meals. Black ethnic groups also showed lower attainment than White ethnic groups between Years 2 and 6, but showed a less pronounced drop in attainment at Year 11. / Conclusions: Those who receive a depression diagnosis during their school career show a drop in attainment in Year 11. Although this pattern was seen among multiple sociodemographic groups, gender, ethnicity and socioeconomic status predict more vulnerable subgroups within this clinical population who might benefit from additional educational support or more intensive treatment

The Yin and Yang of kidney development and Wilms’ tumours

Wilms’ tumor, or nephroblastoma, is the most common pediatric renal cancer. The tumors morphologically resemble embryonic kidneys with a disrupted architecture and are associated with undifferentiated metanephric precursors. Here, we discuss genetic and epigenetic findings in Wilms’ tumor in the context of renal development. Many of the genes implicated in Wilms’ tumorigenesis are involved in the control of nephron progenitors or the microRNA (miRNA) processing pathway. Whereas the first group of genes has been extensively studied in normal development, the second finding suggests important roles for miRNAs in general—and specific miRNAs in particular—in normal kidney development that still await further analysis. The recent identification of Wilms’ tumor cancer stem cells could provide a framework to integrate these pathways and translate them into new or improved therapeutic interventions

Ethical issues of clinical trials in paediatric oncology from 2003 to 2013: a systematic review

A state-of-the art approach to the debates on ethical issues is key in order to gain guidance on research practices involving sick children and adolescents, as well as to identify research avenues in which it might be worth cooperating, to generate better or supplementary evidence. Based on a systematic literature search using MEDLINE, we report the main ethical developments in paediatric oncology clinical trials from 2003–13. The present knowledge about normative and empirical ethical demands in this setting is quantified and summarised in a list of 46 issues. This list primarily aims to provide readers with a comprehensive account of the main decision nodes and professional attitudes that enable families to make a safe, competent, and satisfactory decision about their child's enrolment, or non-participation, in cancer clinical trials. Our systematic Review shows how important it is for professionals to engage in a constant reflection on optimum trial designs, on the effect of offering trial participation on key family dynamics, and on the ways to understand families' needs and values accurately. In view of present scientific developments, we further emphasise the need to enhance societal awareness about research in children and adolescents, to prevent so-called research fatigue in small populations due to multiple solicitations or inadequate legal demands, and to reassess longstanding ethical certainties in the strictest view of promoting sick children's interests. This systematic Review allows a series of questions to be drawn to guide and encourage collective and individual endeavours that should lead to constant improvements in our research practices in paediatric clinical oncology research

Modification of cell wall properties in lettuce improves shelf life

It is proposed that post-harvest longevity and appearance of salad crops is closely linked to pre-harvest leaf morphology (cell and leaf size) and biophysical structure (leaf strength). Transgenic lettuce plants (Lactuca sativa cv. Valeria) were produced in which the production of the cell wall-modifying enzyme xyloglucan endotransglucosylase/hydrolase (XTH) was down-regulated by antisense inhibition. Independently transformed lines were shown to have multiple members of the LsXTH gene family down-regulated in mature leaves of 6-week-old plants and during the course of shelf life. Consequently, xyloglucan endotransglucosylase (XET) enzyme activity and action were down-regulated in the cell walls of these leaves and it was established that leaf area and fresh weight were decreased while leaf strength was increased in the transgenic lines. Membrane permeability was reduced towards the end of shelf life in the transgenic lines relative to the controls and bacteria were evident inside the leaves of control plants only. Most importantly, an extended shelf-life of transgenic lines was observed relative to the non-transgenic control plants. These data illustrate the potential for engineering cell wall traits for improving quality and longevity of salad crops using either genetic modification directly, or by using markers associated with XTH genes to inform a commercial breeding programme