Epithelial-mesenchymal transition softens head and neck cancer cells to facilitate migration in 3D environments.

The biological impact and signalling of epithelial-mesenchymal transition (EMT) during cancer metastasis has been established. However, the changes in biophysical properties of cancer cells undergoing EMT remain elusive. Here, we measured, via video particle tracking microrheology, the intracellular stiffness of head and neck cancer cell lines with distinct EMT phenotypes. We also examined cells migration and invasiveness in different extracellular matrix architectures and EMT-related signalling in these cell lines. Our results show that when cells were cultivated in three-dimensional (3D) environments, the differences in cell morphology, migration speed, invasion capability and intracellular stiffness were more pronounced among different head and neck cancer cell lines with distinct EMT phenotypes than those cultivated in traditional plastic dishes and/or seated on top of a thick layer of collagen. An inverse correlation between intracellular stiffness and invasiveness in 3D culture was revealed. Knock-down of the EMT regulator Twist1 or Snail or inhibition of Rac1 which is a downstream GTPase of Twist1 increased intracellular stiffness. These results indicate that the EMT regulators, Twist1 and Snail and the mediated signals play a critical role in reducing intracellular stiffness and enhancing cell migration in EMT to promote cancer cells invasion.

Prevalence and Trends of Cigarette Smoking Among Military Personnel in Taiwan: Results of 10-Year Anti-Smoking Health Promotion Programs in Military.

OBJECTIVES: The purpose of this study is to evaluate the prevalence and trends of cigarette smoking among young military conscripts, military officers, and military university students during recently 10 years in Taiwan. METHODS: Repeated cross-sectional surveys were conducted annually among young military conscripts and military university students from 2006 to 2014. All the young conscripts were reviewed within 1 month at the military training center and before retiring after 1 year of military services. The military officers were included using purposive sampling from 2004 to 2008 and 2013 to 2014 in different military services. Military university students were included in this study. Freshman and senior students were random sampled as the study subjects. Participants completed a structured questionnaire that included questions on general demographics and health-related behaviors. Current smokers is defined as subjects who smoked ≥1 cigarette/day during the past 30 days or had smoked ≥100 cigarettes in their lifetime or still have the habit of smoking during study. We used a χ2 test to examine the difference between the prevalence of cigarette smoking among different groups. The Cochran-Armitage test for trend was applied to examine the change of prevalence of smoking after repeated cross-sectional surveys among populations. RESULTS: The prevalence of cigarette smoking within military training center and after 1-year military services was 48.6% and 48.1% on 2006, which became 39.2% and 38.6% on 2010, and then further declined to 31.0% and 30.1% on 2014. For military officers, the trends of prevalence of smoking among different military services showed slight decline from 2004 to 2008, but decreased significantly between 2013 and 2014. The prevalence of smoking in 2014 was 32.1%, 32.8%, and 32.4% for the Army, Navy, and Air Force, respectively. More interestingly, the prevalence of smoking of freshman and senior students increased during the first 5 years (2007-2011) of survey and then decreased after 2012. Furthermore, in 2014, the prevalence of smoking decreased as the difference became smaller, 4.5% and 6.1% for freshman and senior, respectively. CONCLUSION: During this 10-year period, the smoking cessation programs include in-class education course, out-door physical training, antismoking clinic, and group therapy. After these military health promoting programs, there are some beneficial effects to decline the prevalence of cigarette smoking for military personnel in Taiwan. However, more active intervention and health promoting programs in prevention and cessation of smoking are needed for the military. The military also have to develop specific approaches and programs to prevent cigarette smoking among conscripts and officers.

Bio- chemical and physical characterizations of mesenchymal stromal cells along the time course of directed differentiation.

Cellular biophysical properties are novel biomarkers of cell phenotypes which may reflect the status of differentiating stem cells. Accurate characterizations of cellular biophysical properties, in conjunction with the corresponding biochemical properties could help to distinguish stem cells from primary cells, cancer cells, and differentiated cells. However, the correlated evolution of these properties in the course of directed stem cells differentiation has not been well characterized. In this study, we applied video particle tracking microrheology (VPTM) to measure intracellular viscoelasticity of differentiating human mesenchymal stromal/stem cells (hMSCs). Our results showed that osteogenesis not only increased both elastic and viscous moduli, but also converted the intracellular viscoelasticity of differentiating hMSCs from viscous-like to elastic-like. In contrast, adipogenesis decreased both elastic and viscous moduli while hMSCs remained viscous-like during the differentiation. In conjunction with bio- chemical and physical parameters, such as gene expression profiles, cell morphology, and cytoskeleton arrangement, we demonstrated that VPTM is a unique approach to quantify, with high data throughput, the maturation level of differentiating hMSCs and to anticipate their fate decisions. This approach is well suited for time-lapsed study of the mechanobiology of differentiating stem cells especially in three dimensional physico-chemical biomimetic environments including porous scaffolds.