Systematic review of school-based interventions to prevent smoking for girls.

BackgroundThe purpose of this review is to study the effect of school-based interventions on smoking prevention for girls.MethodsWe performed a systematic review of articles published since 1992 on school-based tobacco-control interventions in controlled trials for smoking prevention among children. We searched the databases of PubMed, Embase, Web of Science, The Cochrane Databases, CINAHL, Social Science Abstracts, and PsycInfo. Two reviewers independently assessed trials for inclusion and quality and extracted data. A pooled random-effects estimate was estimated of the overall relative risk.ResultsThirty-seven trials were included, of which 16 trials with 24,210 girls were included in the pooled analysis. The overall pooled effect was a relative risk (RR) of 0.96 (95 % confidence interval (CI) 0.86-1.08; I (2)=75 %). One study in which a school-based intervention was combined with a mass media intervention showed more promising results compared to only school-based prevention, and four studies with girl-specific interventions, that could not be included in the pooled analysis, reported statistically significant benefits for attitudes and intentions about smoking and quit rates.ConclusionsThere was no evidence that school-based smoking prevention programs have a significant effect on preventing adolescent girls from smoking. Combining school-based programs with mass media interventions, and developing girl-specific interventions, deserve additional study as potentially more effective interventions compared to school-based-only intervention programs.Systematic review registrationPROSPERO CRD42012002322

Conversations in Science: What children bring to brine shrimps

Evidence tables with studies on school-based interventions with multi-component programs

Bispecific T cell engager (BiTE^®) antibody constructs can mediate bystander tumor cell killing

<div><p>For targets that are homogenously expressed, such as CD19 on cells of the B lymphocyte lineage, immunotherapies can be highly effective. Targeting CD19 with blinatumomab, a CD19/CD3 bispecific antibody construct (BiTE^®), or with chimeric antigen receptor T cells (CAR-T) has shown great promise for treating certain CD19-positive hematological malignancies. In contrast, solid tumors with heterogeneous expression of the tumor-associated antigen (TAA) may present a challenge for targeted therapies. To prevent escape of TAA-negative cancer cells, immunotherapies with a local bystander effect would be beneficial. As a model to investigate BiTE^®-mediated bystander killing in the solid tumor setting, we used epidermal growth factor receptor (EGFR) as a target. We measured lysis of EGFR-negative populations in vitro and in vivo when co-cultured with EGFR-positive cells, human T cells and an EGFR/CD3 BiTE^® antibody construct. Bystander EGFR-negative cells were efficiently lysed by BiTE^®-activated T cells only when proximal to EGFR-positive cells. Our mechanistic analysis suggests that cytokines released by BiTE^®-activated T-cells induced upregulation of ICAM-1 and FAS on EGFR-negative bystander cells, contributing to T cell-induced bystander cell lysis.</p></div

Additional file 4: Table S4. of Systematic review of school-based interventions to prevent smoking for girls

Evidence tables with studies on school-based interventions with multi-component programs

EGFR-negative bystander cells were lysed by BiTE^®-activated T cells when co-cultured with EGFR-positive cells.

<p>NUGC4 (EGFR-positive) and SW620 (EGFR-negative) cells were mixed in various ratios and incubated with T cells (E:T ratio 10:1) and EGFR BiTE^® in duplicate plates. Thousands of cells/well were analyzed, with good agreement between replicate plates. This result was reproducible (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0183390#pone.0183390.s003" target="_blank">S2C Fig</a>). After 48 hours, cells were stained and analyzed as describe in Materials and Methods. Cytotoxicity of (A) EGFR-positive and (B) EGFR-negative cells was measured by nuclear count (N = 2, all data points shown). (C) IFNγ and (D) TNFα were measured using commercially available MSD assays (N = 3, mean +/- sd). (E) T cells from quadruplicate wells were combined and percent CD69+/CD25+ cells determined by flow cytometry.</p

EGFR-negative cells were sensitized to bystander killing by T cell cytokines.

<p>(A) EGFR BiTE^®, T cells and NUGC4 cells (E:T ratio 10:1) were incubated in 96-well plates for 48 hours; supernatants containing T cells were either transferred directly (medium + cells) or clarified by centrifugation prior to transfer (medium only) to 96-well plates containing SW620 cells, or SW620 cells were directly treated with T cells and EGFR BiTE^® (no transfer control); N = 3, mean +/- sd (B) T cells + EGFR BiTE^® + NUGC4 cells were added to the top chamber of Transwell^® assays with 1μm and 5μm membranes; SW620 (or NUGC4 as control) cells were added to the bottom chambers. Percent cytotoxicity in the bottom chambers was determined with CellTiter-Glo^®. (C) SW620 cells were pre-treated for 24 hours +/- cytokines (10ng/ml IFNγ + 5ng/ml TNFα), then incubated for 24 hours with either resting T cells or BiTE^®-activated T cells. Cells were enumerated by nuclear count with cellular imaging; N = 4, mean +/- sd. Significance values: ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.</p

Lysis of bystander EGFR-negative tumor cells in tumor xenografts.

<p>Luciferase-labeled EGFR-negative cells (SW620-LUC), EGFR-positive cells (HCT116) or equal numbers of each cell line were mixed with human T cells (E:T 1:1, where the number of T cells is equal to the number of total combined target cells in mixed implants) and implanted in immunocompromised mice. MEC14 negative control BiTE^® or EGFR BiTE^® was dosed once daily. (A) Tumor growth for 1:1 mixture implants was measured by luminescence on days 8 and 11 using an imaging system. (B) Tumor volume was measured with calipers on day 21. Data represent averages of 5 replicate animals +/- SEM. Significance values: ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.</p

Blockade of IFNγ R1, TNFR1, ICAM-1 or FAS provided partial protection from BiTE^®-mediated cytotoxicity.

<p>(A) SW620 cells were pretreated with either IFNγ R1- or TNFR1-blocking antibodies or mouse IgG1 control antibody at 2 μg/ml (final) for one hour prior to addition of resting T cells or BiTE^®-activated T cells (E:T ratio 10:1) for 48 hours; N = 6, mean +/- sd. SW620 cells were pretreated with cytokines (5ng/ml IFNγ + 10ng/ml TNFα) for 18 hours to induce ICAM-1 and FAS, then incubated with (B) 5 μg/ml anti-ICAM-1 (final) or (C) 2.5 μg/ml anti-FAS (final) neutralizing antibodies (+ cytokines + blocking Ab) or control antibody (no cytokines and + cytokines) for one hour followed by addition of BiTE^®-activated T cells (E:T ratio 10:1) for 24 hours. Cell count was determined by imaging; N = 4, mean +/- sd. Significance values: ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.</p