The Interleukin-11/IL-11 receptor promotes glioblastoma survival and invasion under glucose-starved conditions through enhanced glutaminolysis

Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11

Diffuse choroid plexus hyperplasia: an under-diagnosed cause of hydrocephalus in children?

Hydrocephalus is a common neurological disorder in children and the result of a variety of causes. However, with the advancement of imaging modalities, particularly MRI, previously reported rarer causes of hydrocephalus in children are now being more readily appreciated. We report an 11-year-old boy with diffuse villous hyperplasia of the choroid plexus. He had a ventriculo-peritoneal (VP) shunt in-situ and a prior diagnosis from infancy of congenital aqueduct stenosis as the cause of his hydrocephalus. His current presentation was with further shunt dysfunction. CT and MRI demonstrated enlarged choroid plexuses but did not confirm aqueduct stenosis. CSF overproduction was demonstrated from the externalized ventricular drain. The enlarged choroid plexuses were surgically resected and histology confirmed choroid plexus hyperplasia. Identification of choroid plexus hyperplasia is important since the neurosurgical management of hydrocephalus is not VP shunt insertion, but resection of the hyperplastic choroid plexus

Coexpression analysis of CD133 and CD44 identifies proneural and mesenchymal subtypes of glioblastoma multiforme

Accumulating evidence suggests that the stem cell markers CD133 and CD44 indicate molecular subtype in Glioblastoma Multiforme (GBM). Gene coexpression analysis of The Cancer Genome Atlas GBM dataset was undertaken to compare markers of the Glioblastoma Stem-Progenitor Cell (GSPC) phenotype. Pearson correlation identified genes coexpressed with stem cell markers, which were then used to build a gene signature that classifies patients based on a CD133 coexpression module signature (CD133-M) or CD44-M subtype. CD133-M tumors were enriched for the Proneural (PN) GBM subtype compared to Mesenchymal (MES) subtype for CD44-M tumors. Gene set enrichment identified DNA replication/cell cycle genes in the CD133-M and invasion/migration in CD44-M, while functional experiments showed enhanced cellular growth in CD133 expressing cells and enhanced invasion in cells expressing CD44. As with the 4 major molecular subtypes of GBM, there was no long-term survival difference between CD44-M and CD133-M patients, although CD44-M patients responded better to temozolomide while CD133-M patients benefited from radiotherapy. The use of a targeted coexpression approach to predict functional properties of surface marker expressing cells is novel, and in the context of GBM, supports accumulating evidence that CD133 and CD44 protein marker expression correlates with molecular subtype.status: publishe

Sexual function in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

BACKGROUND: Despite its importance to sexual health and wellbeing, sexual function is given little attention in sexual health policy. Population-based studies are needed to understand sexual function across the life course. METHODS: We undertook a probability sample survey (the third National Survey of Sexual Attitudes and Lifestyles [Natsal-3]) of 15,162 individuals aged 16-74 years who lived in Britain (England, Scotland, and Wales). Interviews were done between Sept 6, 2010, and Aug 31, 2012. We assessed the distribution of sexual function by use of a novel validated measure (the Natsal-SF), which assessed problems with individual sexual response, sexual function in a relationship context, and self-appraisal of sex life (17 items; 16 items per gender). We assess factors associated with low sexual function (defined as the lowest quintile of distribution of Natsal-SF scores) and the distribution of components of the measure. Participants reporting one or more sexual partner in the past year were given a score on the Natsal-SF (11,690 participants). 4122 of these participants were not in a relationship for all of the past year and we employed the full information maximum likelihood method to handle missing data on four relationship items. FINDINGS: We obtained data for 4913 men and 6777 women for the Natsal-SF. For men and women, low sexual function was associated with increased age, and, after age-adjustment, with depression (adjusted odds ratio 3·70 [95% CI 2·90-4·72] for men and 4·11 [3·36-5·04] for women) and self-reported poor health status (2·63 [1·73-3·98] and 2·41 [1·72-3·39]). Low sexual function was also associated with experiencing the end of a relationship (1·52 [1·18-1·95] and 1·77 [1·44-2·17]), inability to talk easily about sex with a partner (2·36 [1·94-2·88] and 2·82 [2·28-3·48]), and not being happy in the relationship (2·89 [2·32-3·61] and 4·10 [3·39-4·97]). Associations were also noted with engaging in fewer than four sex acts in the past 4 weeks (3·13 [2·58-3·79] and 3·38 [2·80-4·09]), having had same sex partners (2·28 [1·56-3·35] and 1·60 [1·16-2·20]), paying for sex (in men only; 2·62 [1·46-4·71]), and higher numbers of lifetime sexual partners (in women only; 2·12 [1·68-2·67] for ten or more partners). Low sexual function was also associated with negative sexual health outcomes such as experience of non-volitional sex (1·98 [1·14-3·43] and 2·18 [1·79-2·66]) and STI diagnosis (1·50 [1·06-2·11] and 1·83 [1·35-2·47]). Among individuals reporting sex in the past year, problems with sexual response were common (41·6% of men and 51·2% of women reported one or more problem) but self-reported distress about sex lives was much less common (9·9% and 10·9%). For individuals in a sexual relationship for the past year, 23·4% of men and 27·4% of women reported an imbalance in level of interest in sex between partners, and 18·0% of men and 17·1% of women said that their partner had had sexual difficulties. Most participants who did not have sex in the past year were not dissatisfied, distressed, or avoiding sex because of sexual difficulties. INTERPRETATION: Wide variability exists in the distribution of sexual function scores. Low sexual function is associated with negative sexual health outcomes, supporting calls for a greater emphasis on sexual function in sexual health policy and interventions. FUNDING: Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health

A comprehensive meta-analysis of circulation miRNAs in glioma as potential diagnostic biomarker

<div><p>Glioma is the most common malignant intracranial tumour. Recently, several publications have suggested that miRNAs can be used as potential diagnostic biomarkers of glioma. Here we performed a meta-analysis to identify the diagnostic accuracy of differentially expressed circulating miRNAs in gliomas. Using PubMed, Medline and Cochrane databases, we searched for studies which evaluated a single or panel of miRNAs from circulating blood as potential biomarkers of glioma. Sixteen publications involving 23 studies of miRNAs from serum or plasma met our criteria and were included in this meta-analysis. The pooled diagnostic parameters were calculated by random effect models and overall diagnostic performance of altered miRNAs was illustrated by the summary receiver operator characteristic (SROC) curves. The pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) from each study were calculated. The pooled PLR, NLR and Diagnostic Odds Ratio were 6.39 (95% CI, 4.61–8.87), 0.15 (95% CI, 0.11–0.21) and 41.91 (95% CI, 23.15–75.88), respectively. The pooled sensitivity, specificity and area under the curve (AUC) were 0.87 (95% CI, 0.82–0.91), 0.86 (95% CI, 0.82–0.90) and 0.93 (95% CI, 0.91–0.95), respectively. This meta-analysis demonstrated that circulating miRNAs are capable of distinguishing glioma from healthy controls. Circulating miRNAs are promising diagnostic biomarkers for glioma and can potentially be used as a non-invasive early detection.</p></div

Interleukin-11/IL-11 receptor promotes glioblastoma cell proliferation, epithelial–mesenchymal transition, and invasion

Glioblastoma is highly proliferative and invasive. However, the regulatory cytokine networks that promote glioblastoma cell proliferation and invasion into other areas of the brain are not fully defined. In the present study, we define a critical role for the IL-11/IL-11

Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity

Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.status: publishe

Forest plots of all 16 studies included in this meta-analysis.

<p>The pooled <b>A)</b> sensitivity and <b>B)</b> specificity is 0.87 and 0.86, respectively of miRNAs in diagnosis of glioma.</p

Diagram of SROC curves describing the diagnostic performance of miRNAs.

<p><b>A)</b> The PLR and NLR is 6.39 and 0.15 respectively, showing the pre-test probability set as 25%, the positive and negative post-test probability of 68% and 5%, respectively. <b>B)</b> The AUC is 0.93 (95%CI, 0.91–0.95). Each number within a circle represents the order of study identifier in Fig 3.</p