Activiteit

To examine whether the family integrated care (FICare) programme, a multifaceted approach which enables parents to be engaged as primary caregivers in the neonatal intensive care unit, impacts infant neurodevelopment and growth at 18 months’ corrected age.

Prospective cohort study of infants born <29 weeks’ gestational age (GA) who participated in the FICare cluster randomised control trial (cRCT) and were assessed in the Canadian Neonatal Follow-Up Network (CNFUN). The primary outcome measure, Cognitive or Language composite score <85 on the Bayley-III, was compared between FICare exposed and routine care children using logistic regression, adjusted for potential confounders and employing generalised estimation equations to account for clustering of infants within sites.

Of 756 infants <29 weeks’ GA in the FICare cRCT, 505 were enrolled in CNFUN and 455 were assessed (238 FICare, 217 control). Compared with controls, FICare infants had significantly higher incidence of intraventricular haemorrhage (IVH) (19.5% vs 11.7%, p=0.024) and higher proportion of employed mothers (76.6% vs 73.6%, p=0.043). There was no significant difference in the odds of the primary outcome (adjusted OR 0.92 (0.59 to 1.42) FiCare vs Control) on multivariable analyses adjusted for GA, IVH and maternal employment. However, Bayley-III Motor scores (adjusted difference in mean (95% CI) 3.87 (1.22 to 6.53) and body mass index 0.67 (0.36 to 0.99) were higher in the FICare group.

Very preterm infants exposed to FICare had no significant difference in incidence of cognitive or language delay but had better motor development.

Participants in this cohort study were previously enrolled in a registered trial NCT01852695.

Participants in this cohort study were previously enrolled in a registered trial NCT01852695.Tumor metabolism supports the energetic and biosynthetic needs of rapidly proliferating cancer cells and modifies intra- and intercellular signaling to enhance cancer cell invasion, metastasis, and immune evasion. Prostate cancer exhibits unique metabolism with high rates of de novo fatty acid synthesis driven by activation of the androgen receptor (AR). Increasing evidence suggests that activation of this pathway is functionally important to promote prostate cancer aggressiveness. However, the mechanisms by which fatty acid synthesis are beneficial to prostate cancer have not been well defined. In this Review, we summarize evidence indicating that fatty acid synthesis drives progression of prostate cancer. We also explore explanations for this phenomenon and discuss future directions for targeting this pathway for patient benefit.ENO1 (α-enolase) expression is significantly correlated with reduced survival and poor prognosis in many cancer types, including lung cancer. However, the function of ENO1 in carcinogenesis remains elusive. In this study, we found that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors and is associated with poor overall survival of patients with lung cancer. Knockdown of ENO1 decreased cancer cell proliferation and invasiveness, whereas overexpression of ENO1 enhanced these processes. Moreover, ENO1 expression promoted tumor growth in orthotopic models and enhanced lung tumor metastasis in tail-vein injection models. These effects were mediated by upregulation of mesenchymal markers N-cadherin and vimentin and the epithelial-to-mesenchymal transition regulator SLUG, along with concurrent downregulation of E-cadherin. Mechanistically, ENO1 interacted with hepatocyte growth factor receptor (HGFR) and activated HGFR and Wnt signaling via increased phosphorylation of HGFR and the Wnt coreceptor LRP5/6. Myrcludex B in vivo Activation of these signaling axes decreased GSK3β activity via Src-PI3K-AKT signaling and inactivation of the β-catenin destruction complex to ultimately upregulate SLUG and β-catenin. In addition, we generated a chimeric anti-ENO1 mAb (chENO1-22) that can decrease cancer cell proliferation and invasion. chENO1-22 attenuated cancer cell invasion by inhibiting ENO1-mediated GSK3β inactivation to promote SLUG protein ubiquitination and degradation. Moreover, chENO1-22 prevented lung tumor metastasis and prolonged survival in animal models. Taken together, these findings illuminate the molecular mechanisms underlying the function of ENO1 in lung cancer metastasis and support the therapeutic potential of a novel antibody targeting ENO1 for treating lung cancer. 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Nuclear-derived dsRNA is packaged into extracellular vesicles and subsequently recognized by toll-like receptor 3 (TLR3) to activate TBK1 and downstream MHC class I expression in an autocrine or paracrine manner before being degraded in lysosomes. MYC suppressed loading of dsRNA onto TLR3 and its subsequent degradation via association with MIZ1. Collectively, these findings suggest that MYC and MIZ1 suppress a surveillance pathway that signals perturbances in mRNA processing to the immune system, which facilitates immune evasion in pancreatic ductal adenocarcinoma.Monoclonal antibodies (mAb) are a major component of cancer therapy. In this review, we summarize the different therapeutic mAbs that have been successfully developed against various tumor-expressed antigens and examine our current understanding of their different mechanisms of anti-tumor action. These mechanisms of action (MOA) largely center on the stimulation of different innate immune effector processes, which appear to be principally responsible for the efficacy of most unconjugated mAb therapies against cancer. This is evident in studies of mAbs targeting antigens for hematologic cancers, with emerging data also demonstrating the critical nature of innate immune-mediated mechanisms in the efficacy of anti-HER2 mAbs against solid HER2+ cancers. While HER2-targeted mAbs were originally described as inhibitors of HER2-mediated signaling, multiple studies have since demonstrated these mAbs function largely through their engagement with Fc receptors to activate innate immune effector functions as well as complement activity.