Mechanism of epithelial-mesenchymal transition in cancer and its regulation by natural compounds.

Epithelial-mesenchymal transition (EMT) is a complex process with a primordial role in cellular transformation whereby an epithelial cell transforms and acquires a mesenchymal phenotype. This transformation plays a pivotal role in tumor progression and self-renewal, and exacerbates resistance to apoptosis and chemotherapy. EMT can be initiated and promoted by deregulated oncogenic signaling pathways, hypoxia, and cells in the tumor microenvironment, resulting in a loss-of-epithelial cell polarity, cell-cell adhesion, and enhanced invasive/migratory properties. Numerous transcriptional regulators, such as Snail, Slug, Twist, and ZEB1/ZEB2 induce EMT through the downregulation of epithelial markers and gain-of-expression of the mesenchymal markers. Additionally, signaling cascades such as Wnt/ß-catenin, Notch, Sonic hedgehog, nuclear factor kappa B, receptor tyrosine kinases, PI3K/AKT/mTOR, Hippo, and transforming growth factor-ß pathways regulate EMT whereas they are often deregulated in cancers leading to aberrant EMT. Furthermore, noncoding RNAs, tumor-derived exosomes, and epigenetic alterations are also involved in the modulation of EMT. Therefore, the regulation of EMT is a vital strategy to control the aggressive metastatic characteristics of tumor cells. Despite the vast amount of preclinical data on EMT in cancer progression, there is a lack of clinical translation at the therapeutic level. In this review, we have discussed thoroughly the role of the aforementioned transcription factors, noncoding RNAs (microRNAs, long noncoding RNA, circular RNA), signaling pathways, epigenetic modifications, and tumor-derived exosomes in the regulation of EMT in cancers. We have also emphasized the contribution of EMT to drug resistance and possible therapeutic interventions using plant-derived natural products, their semi-synthetic derivatives, and nano-formulations that are described as promising EMT blockers.

Emergency with Resiliency Equals Efficiency - Challenges of an EMT-3 in Nepal.

The 7.8 MW (moment magnitude scale) earthquake that hit Nepal on April 25, 2015 caused significant casualties and serious damage to infrastructure.The Israeli Emergency Medical Team (IEMT; later verified as EMT-3) was deployed 80 hours after the earthquake. A Forward Disaster Scout Team (FDST) that was dispatched to the disaster area a few hours after the disaster relayed pre-deployment information.The EMT staff was comprised of 42 physicians. A total of 1,668 patients were treated. The number of non-trauma cases increased as the days went by. The hospitalization rate was 31%. Wound debridement procedures were the most common operations performed. YitzhakA, MerinO, HalevyJ, TarifB. Emergency with resiliency equals efficiency- challenges of an EMT-3 in Nepal. Prehosp Disaster Med. 2018;33(6):673-677.