ß2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer.

Chronic stress accelerates metastasis - the main cause of death in cancer patients - through the activation of ß-adrenoceptors (ßARs). We have previously shown that ß2AR signaling in MDA-MB-231(HM) breast cancer cells, facilitates invadopodia formation and invasion in vitro. However, in the tumor microenvironment where many stromal cells also express ßAR, the role of ß2AR signaling in tumor cells in metastasis is unclear. Therefore, to investigate the contribution of ß2AR signaling in tumor cells to metastasis in vivo, we used RNA interference to generate MDA-MB-231(HM) breast cancer cells that are deficient in ß2AR. ß2AR knockdown in tumor cells reduced the proportion of cells with a mesenchymal-like morphology and, as expected, reduced tumor cell invasion in vitro. Conversely, overexpression of ß2AR in low metastatic MCF-7 breast cancer cells induced an invasive phenotype. Importantly, we found that knockdown of ß2AR in tumor cells significantly reduced the impact of stress on metastasis in vivo. These findings highlight a crucial role for ß2AR tumor cell signaling in the adverse effects of stress on metastasis, and indicate that it may be necessary to block ß2AR on tumor cells to fully control metastatic progression.

Mental health of adolescents in Myanmar: A systematic review of prevalence, determinants and interventions.

Adolescence is a developmental phase where mental disorders typically manifest and where platforms for response (including schools and health services) change rapidly. However, data to inform public mental health responses are limited, including in countries like Myanmar which has a large adolescent population and where mental health has been identified as a priority of policy. In this paper we sought to systematically review the peer-reviewed and grey literature to determine (i) the prevalence of mental disorder among adolescents in Myanmar, (ii) determinants of mental disorder and (iii) interventions that have been implemented and evaluated. Nine publications met inclusion criteria (7 peer-reviewed and 2 grey literature) that included 7 publications reporting prevalence, 6 reporting correlates and one an intervention. The available data from the 2016 Global School-based Health Survey highlight that depression (27.2%) and suicidal ideation (9.4%) are prevalent in Myanmar, and these rates are substantially higher than regional averages. The limited available data on correlates identified violence and bullying, alcohol and substance use, and home, family and community security and cohesion as being closely related to mental health for adolescents. Only one study focussed on interventions and this found mindfulness meditation training to be an effective approach for young people whose parents were affected by HIV. These findings underscore the need to address adolescent mental health in Myanmar, but also to invest in better data collection efforts.