ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

Frequent tumor relapse in hepatocellular carcinoma (HCC) has been commonly attributed to the presence of residual cancer stem cells (CSCs) after conventional treatments. We have previously identified and characterized CD133 to mark a specific CSC subset in HCC. In the present study, we found endogenous and secretory annexin A3 (ANXA3) to play pivotal roles in promoting cancer and stem cell-like features in CD133+ liver CSCs through a dysregulated JNK pathway. Blockade of ANXA3 with an anti-ANXA3 monoclonal antibody in vitro as well as in human HCC xenograft models resulted in a significant reduction in tumor growth and self-renewal. Clinically, ANXA3 expression in HCC patient sera closely associated with aggressive clinical features. Our results suggest that ANXA3 can serve as a novel diagnostic biomarker and that the inhibition of ANXA3 may be a viable therapeutic option for the treatment of CD133+ liver-CSC-driven HCC. © 2015 The Authors.published_or_final_versio

Health services research into postnatal depression : results from a preliminary cross-cultural study

Background: Little is known about the availability and uptake of health and welfare services by women with postnatal depression in different countries. Aims: Within the context of a cross- cultural research study, to develop and test methods for undertaking quantitative health services research in postnatal depression. Method: Interviews with service planners and the collation of key health indicators were used to obtain a profile of service availability and provision. A service use questionnaire was developed and administered to a pilot sample in a number of European study centres. Results: Marked differences in service access and use were observed between the centres, including postnatal nursing care and contacts with primary care services.Rates of use of specialist services were generally low.Common barriers to access to care included perceived service quality and responsiveness. On the basis of the pilot work, a postnatal depression version of the Service Receipt Inventory was revised and finalised. Conclusions: This preliminary study demonstrated the methodological feasibility of describing and quantifying service use, highlighted the varied and often limited use of care in this population, and indicated the need for an improved understanding of the resource needs and implications of postnatal depression

Intraspecific variation in leaf traits facilitates the occurrence of trees at the Amazonia–Cerrado transition

The ability of plant species to adjust key functional traits through intraspecific variation may determine their success in persisting on our planet in the future, especially in unstable habitats, such as the Amazonia–Cerrado transition zone. We assessed intraspecific variation in 12 leaf morphological and anatomical traits for four tree species along a savanna–forest gradient, including rocky cerrado, typical cerrado and woodland savanna. Generally, all evaluated species showed great intraspecific variation. Our findings demonstrate that trees occurring in the woodland savanna are potentially more vulnerable to climate change, while in the cerrado the individuals presented higher tolerance to water deficit and high temperatures. Trees occurring in open-canopy habitats showed smaller stomata, higher stomata and trichome densities, compared to the same species growing in the woodland savanna. In contrast, the individuals in the woodland savanna shift leaf traits to increase resource acquisition (e.g. light), showing higher specific leaf area and larger stomata, compared to cerrado individuals. We have shown that vegetation-induced shifts in leaf morphological and anatomical traits are a major effect in within-species variability, with consequences for persistence and tolerance of species under future climatic conditions

Postnatal depression across countries and cultures : a qualitative study

Background: Postnatal depression seems to be a universal condition with similar rates in different countries. However, anthropologists question the cross-cultural equivalence of depression, particularly at a life stage so influenced by cultural factors. Aims: To develop a qualitative method to explore whether postnatal depression is universally recognised, attributed and described and to enquire into people’s perceptions of remedies and services for morbid states of unhappiness within the context of local services. Method: The study took place in 15 centres in 11 countries and drew on three groups of informants: focus groups with new mothers, interviews with fathers and grandmothers, and interviews with health professionals.Textual analysis of these three groups was conducted separately in each centre and emergent themes compared across centres. Results: All centres described morbid unhappiness after childbirth comparable to postnatal depression but not all saw this as an illness remediable by health interventions. Conclusions: Although the findings of this study support the universality of a morbid state of unhappiness following childbirth, they also support concerns about the cross-cultural equivalence of postnatal depression as an illness requiring the intervention of health professionals; this has implications for future research

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L