The prevalence of overweight and obesity is increasing worldwide, and the evidence base for a link between obesity and cancer is growing. In the United States, approximately 85,000 new cancer cases per year are related to obesity. Recent research has found that as the body mass index increases by 5 kg/m2, cancer mortality increases by 10%. Additionally, studies of patients who have had bariatric surgery for weight loss report reductions in cancer incidence and mortality, particularly for women. The goal of this review is to provide an update of recent research, with a focus on epidemiologic studies on the link between obesity and cancer. In addition, we will briefly review hypothesized mechanisms underlying the relationship between obesity and cancer. High priorities for future research involve additional work on the underlying mechanisms, and trials to examine the effect of lifestyle behavior change and weight loss interventions on cancer and intermediate biomarkers.

Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten survival in glioblastoma. Dexamethasone-induced anti-proliferative effects may confer protection from radiotherapy- and chemotherapy-induced genotoxic stress. This study highlights the importance of identifying alternative agents such as vascular endothelial growth factor antagonists for managing oedema in glioblastoma patients. Beyond the established adverse effect profile of protracted corticosteroid use, this analysis substantiates the request for prudent and restricted use of corticosteroids in glioblastoma.

Functional magnetic resonance imaging studies have reported reduced activation in parietotemporal and occipitotemporal areas in adults and children with developmental dyslexia compared to controls during reading and reading related tasks. These patterns of regionally reduced activation have been linked to behavioral impairments of reading-related processes (e.g., phonological skills and rapid automatized naming). The observed functional and behavioral differences in individuals with developmental dyslexia have been complemented by reports of reduced gray matter in left parietotemporal, occipitotemporal areas, fusiform and lingual gyrus and the cerebellum. An important question for education is whether these neural differences are present before reading is taught. Developmental dyslexia can only be diagnosed after formal reading education starts. However, here we investigate whether the previously detected gray matter alterations in adults and children with developmental dyslexia can already be observed in a small group of pre-reading children with a family-history of developmental dyslexia compared to age and IQ-matched children without a family-history (N = 20/mean age: 5:9 years; age range 5:1–6:5 years). Voxel-based morphometry revealed significantly reduced gray matter volume indices for pre-reading children with, compared to children without, a family-history of developmental dyslexia in left occipitotemporal, bilateral parietotemporal regions, left fusiform gyrus and right lingual gyrus. Gray matter volume indices in left hemispheric occipitotemporal and parietotemporal regions of interest also correlated positively with rapid automatized naming. No differences between the two groups were observed in frontal and cerebellar regions. This discovery in a small group of children suggests that previously described functional and structural alterations in developmental dyslexia may not be due to experience-dependent brain changes but may be present at birth or develop in early childhood prior to reading onset. Further studies using larger sample sizes and longitudinal analyses are needed in order to determine whether the identified structural alterations may be utilized as structural markers for the early identification of children at risk, which may prevent the negative clinical, social and psychological outcome of developmental dyslexia.

No abstract

Purpose: Selective cyclooxygenase-2 (COX-2) inhibitors may suppress carcinogenesis by both COX-2-dependent and COX-2-independent mechanisms. The primary purpose of this study was to evaluate whether celecoxib or rofecoxib, two widely used selective COX-2 inhibitors, possess COX-2-independent antitumor activity.Experimental Design: PC3 and LNCaP human prostate cancer cell lines were used to investigate the growth inhibitory effects of selective COX-2 inhibitors in vitro. To complement these studies, we evaluated the effect of celecoxib on the growth of PC3 xenografts.Results: COX-1 but not COX-2 was detected in PC3 and LNCaP cells. Clinically achievable concentrations (2.5-5.0 Mmol/L) of celecoxib inhibited the growth of both cell lines in vitro, whereas rofecoxib had no effect over the same concentration range. Celecoxib inhibited cell growth by inducing a G 1 cell cycle block and reducing DNA synthesis. Treatment with celecoxib also led to dosedependent inhibition of PC3 xenograft growth without causing a reduction in intratumor prostaglandin E 2 . Inhibition of tumor growth occurred at concentrations (2.37-5.70 Mmol/L) of celecoxib in plasma that were comparable with the concentrations required to inhibit cell growth in vitro. The highest dose of celecoxib led to a 52% reduction in tumor volume and an f50% decrease in both cell proliferation and microvessel density. Treatment with celecoxib caused a marked decrease in amounts of cyclin D1 both in vitro and in vivo.Conclusions: Two clinically available selective COX-2 inhibitors possess different COX-2-independent anticancer properties. The anticancer activity of celecoxib may reflect COX-2-independent in addition to COX-2-dependent effects.

Within the last decade there has been an increase in the use of structural and functional magnetic resonance imaging (fMRI) to investigate the neural basis of human perception, cognition and behavior 1, 2 . Moreover, this non-invasive imaging method has grown into a tool for clinicians and researchers to explore typical and atypical brain development. Although advances in neuroimaging tools and techniques are apparent, (f)MRI in young pediatric populations remains relatively infrequent 2 . Practical as well as technical challenges when imaging children present clinicians and research teams with a unique set of problems 3, 2 . To name just a few, the child participants are challenged by a need for motivation, alertness and cooperation. Anxiety may be an additional factor to be addressed. Researchers or clinicians need to consider time constraints, movement restriction, scanner background noise and unfamiliarity with the MR scanner environment 2,4-10 . A progressive use of functional and structural neuroimaging in younger age groups, however, could further add to our understanding of brain development. As an example, several research groups are currently working towards early detection of developmental disorders, potentially even before children present associated behavioral characteristics e.g.11 . Various strategies and techniques have been reported as a means to ensure comfort and cooperation of young children during neuroimaging sessions. Play therapy 12 , behavioral approaches 13,14,15,[16][17][18] and simulation 19 , the use of mock scanner areas 20,21 , basic relaxation 22 and a combination of these techniques 23 have all been shown to improve the participant's compliance and thus MRI data quality. Even more importantly, these strategies have proven to increase the comfort of families and children involved 12 . One of the main advances of such techniques for the clinical practice is the possibility of avoiding sedation or general anesthesia (GA) as a way to manage children's compliance during MR imaging sessions 19,20 . In the current video report, we present a pediatric neuroimaging protocol with guidelines and procedures that have proven to be successful to date in young children. ProtocolWe have incorporated general experimental testing guidelines as well as MRI specific approaches 12-23 into one complete neuroimaging protocol intended to guide researchers and clinicians during neuroimaging sessions with awake children as young as four years of age. First, we aim to emphasize general testing guidelines adapted for MRI examinations. Second, we provide a hands-on, step-by-step description of our neuroimaging protocol. In our experience, a single session of approximately 2.5 hours (including a maximal imaging time of 45-60 minutes) is sufficient to train and guide a child through a neuroimaging session. General GuidelinesAs in every testing session with pediatric populations, general guidelines and recommendations for how best to work with young children should be considered 24 . We highlight comfor...

Plant roots retain developmental plasticity and respond to environmental stresses or exogenous plant growth regulators by undergoing profound morphological and physiological alteration. In this study, we investigated the effects of exogenous ABA on root growth and development in Taichung native 1 (TN1) rice. Exogenous application of 10 microM ABA leads to swelling, root hair formation and initiation of lateral root primodia in the tips of young, seminal rice roots. Cortex cells increased in size and were irregularly shaped. ABA treatment significantly increased 2, 3, 5-triphenyl tetrazolium chloride (TTC) reductase ability in the root tips and the exudation rate of xylem sap. In addition, the K(+) ion content in xylem sap increased nearly 2-fold, but not that of Ca(2+) or Mg(2+). Analysis of proteins expressed in the root tips identified several ABA-induced or -repressed proteins, including actin depolymerization factor (ADF), late embryo abundant protein (LEA), putative steroid membrane-binding protein, ferredoxin thionine reductase and calcium-binding protein. The effects of ABA on root morphogenesis change were Ca(2+) dependent and required the participation of calmodulin and de novo protein synthesis. A model is presented that illustrates how ABA acts through a potential cellular and signal transduction mechanism to induce morphological and physiological changes in rice roots.

Children grow, but adults do not. The cessation of growth in multiple organs is the end result of a progressive decline in cell proliferation beginning in early life. The mechanisms responsible for this growth deceleration are largely unknown. Using expression microarray and real-time PCR, we identified a common program of gene expression in lung, kidney, and liver during growth deceleration in juvenile rats. Gene ontology analyses and siRNA-mediated knockdown in vitro indicated that many of the down-regulated genes are growth promoting. Down-regulated genes in the program showed declining histone H3K4 trimethylation with age, implicating underlying epigenetic mechanisms. To investigate the physiological processes driving the genetic program, a tryptophan-deficient diet was used to temporarily inhibit juvenile growth in newborn rats for 4 wk. Afterward, microarray analysis showed that the genetic program had been delayed, implying that it is driven by body growth itself rather than age. Taken together, the findings suggest that growth in early life induces progressive down-regulation of a large set of proliferation-stimulating genes, causing organ growth to slow and eventually cease.