Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination

Objective：To investigate the effects of E7080 and N5-（1-iminoethyl）-L-ornithine dihydrochloride （L-NIO）on colorectal cancer alone and in combination.Methods：HT29 colorectal cancer cell line from Sap Institute was used.Real-time cell analysis （xCELLigence system） was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation.While apoptosis was determined with Annexin V staining,and the effect of agents on angiogenesis was determined with chorioallantoic membrane （CAM） model.Results：We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration （IC50） value of 5.60×10-8 mol/L.Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells.Antiangiogenic scores of E7080 were 1.2,t.0 and 0.6 for 100,10 and 1 nmol/L E7080 concentrations,respectively.Furthermore,apoptosis has been detected in 71％ of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect.Meanwhile administration of L-NIO alone did not show any effect,but the combination of E7080 with L-NIO increased the antiproliferative,antiangiogenic and apoptotic effects of E7080.Conclusions：Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors.Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080.     

Cohort Profile: Quebec Longitudinal Study of Child Development (QLSCD)

Purpose

The Quebec Longitudinal Study of Child Development (QLSCD) was designed to examine the long-term associations of preschool physical, cognitive, social, and emotional development with biopsychosocial development across childhood, adolescence, and young adulthood.

Methods

QLSCD is an ongoing prospective cohort including 2120 singletons born in 1997/1998 in the Canadian province of Quebec. So far, data have been collected annually or every 2 years from child ages 5 months to 21 years. The cohort currently includes 1245 participants. Data available include a range of environmental (e.g., family characteristics, child behaviour, educational attainment, mental health), biological (e.g., hair cortisol, genetic, epigenetic), and administrative data.

Results

QLSCD has contributed to the understanding of children’s psychosocial development, including the development of physical aggression and anxiety. QLSCD articles have advanced scientific knowledge on the influence of early childhood factors on childhood, adolescent, and young adult mental health, including the effect of participation in early childcare on cognitive and behavioural development, the developmental origins of adolescent and young adult mental health problems and suicide risk, and the development of interpersonal difficulties (e.g., peer victimisation) from preschool years to adolescence.

Conclusion

QLSCD has given major contributions to our understanding of the link between different aspects of child development and biopsychosocial development during the first two decades of life. Unique features include the presence of environmental, biological, and administrative data, long-term follow-up with frequent data collections, and use of data from multiple informants, including teachers, mothers, fathers, and the children themselves.

     

Maternal depression symptoms and internalising problems in the offspring: the role of maternal and family factors

Maternal depression symptoms (MDS) are a robust risk factor for internalising problems (IP) in the offspring. However, the relative importance of MDS and other factors associated with it (i.e. other types of maternal psychopathology, maternal parenting practices, family characteristics) is not well understood. To (a) identify a group of children with high levels of IP between 6 and 12 years using combined maternal and teacher assessments and (b) to quantify the associations between trajectories of MDS during early childhood and children’s IP trajectories before and after controlling for family factors associated with MDS. MDS and family factors were assessed in a population-based sample in Canada (n = 1537) between 5 months and 5 years. The outcome variable was membership in trajectories of teacher- and mother-rated IP between ages 6 and 12 years. Family factors were included as covariates in a multinomial logistic regression model. There was a strong association between MDS and children’s atypically high levels of IP in unadjusted analyses [OR 4.14 (95% CI 2.60; 6.61)]. The association was reduced, but remained strong [2.60 (1.55; 4.36)] when maternal psychopathology, maternal parenting, and family socioeconomic status were entered in the model. MDS, maternal anxiety, and low parental self-efficacy were associated with offspring’s high IP trajectories. MDS is associated with high levels of children’s IP independently of other maternal and family characteristics. Intervention targeting maternal psychopathology and parenting self-efficacy and testing the impact on children’s IP would provide information on the putative causal pathways between maternal and offspring’s symptomatology.     

Maternal depressive symptoms and children’s cognitive school readiness: the role of gene-environment interplay

Archives of Women's Mental Health - Maternal depressive symptoms are a robust risk factor for poor cognitive outcomes in children, yet the role of gene-environment interplay in this association...     

Maternal depressive symptoms and early childhood cognitive development: a review of putative environmental mediators

Archives of Women's Mental Health - Despite the abundance of research investigating the associations between maternal depressive symptoms (MDS) and children’s cognitive development,...     

Distributing insecticide-treated bednets during measles vaccination: a low-cost means of achieving high and equitable coverage

OBJECTIVE: To achieve high and equitable coverage of insecticide-treated bednets by integrating their distribution into a measles vaccination campaign. METHODS: In December 2002 in the Lawra district in Ghana, a measles vaccination campaign lasting 1 week targeted all children aged 9 months-15 years. Families with one or more children less than five years old were targeted to receive a free insecticide-treated bednet. The Ghana Health Service, with support from the Ghana Red Cross and UNICEF, provided logistical support, volunteer workers and social mobilization during the campaign. Volunteers visited homes to inform caregivers about the campaign and encourage them to participate. We assessed pre-campaign coverage of bednets by interviewing caregivers leaving vaccination and distribution sites. Five months after distribution, a two-stage cluster survey using population-proportional sampling assessed bednet coverage, retention and use. Both the pre-campaign and post-campaign survey assessed household wealth using an asset inventory. FINDINGS: At the campaign exit interview 636/776 (82.0%) caregivers reported that they had received a home visit by a Red Cross volunteer before the campaign and that 32/776 (4.1%) of the youngest children in each household who were less than 5 years of age slept under an insecticide-treated bednet. Five months after distribution caregivers reported that 204/219 (93.2%) of children aged 9 months to 5 years had been vaccinated during the campaign; 234/248 (94.4%) of households were observed to have an insecticide-treated bednet; and 170/249 (68.3%) were observed to have a net hung over a bed. Altogether 222/248 (89.5%) caregivers reported receiving at least one insecticide-treated bednet during the campaign, and 153/254 (60.2%) said that on the previous night their youngest child had slept under a bednet received during the campaign. For households in the poorest quintile, post-campaign coverage of insecticide-treated bednets was 10 times higher than pre-campaign coverage of households in the wealthiest quintile (46/51 (90.2%) versus 14/156 (9.0%)). The marginal operational cost was 0.32 US dollars per insecticide-treated bednet delivered. CONCLUSION: These findings suggest that linking bednet distribution to measles vaccination campaigns may provide an important opportunity for achieving high and equitable coverage of bednets.