The epithelial-mesenchymal transition (EMT) induced by chemotherapeutic agents promotes malignant tumor progression; however, the mechanism underlying the drug-induced EMT remains unclear. In this study, we reported that miR-448 is the most downregulated microRNA following chemotherapy. Suppression of miR-448 correlated with EMT induction in breast cancer in vitro and in vivo. With the use of chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448 suppression induces EMT by directly targeting special AT-rich sequence-binding protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby, increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as well as nuclear factor jB (NF-jB) activation. On the other hand, we also found that the adriamycin-activated NF-jB directly binds the promoter of miR-448 suppressing its transcription, suggesting a positive feedback loop between NF-jB and miR-448. Furthermore, all patients who received cyclophosphamide (CP), epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of mesenchymal phenotypes. These findings reveal an underlying regulatory pathway, in which the autoregulation between NF-jB and miR-448 is important for restrain miR-448 suppression upon chemotherapy and may have a role in the regulation of chemotherapy-induced EMT. Disruption of the NF-jB-miR-448 feedback loop during clinical treatment may improve the chemotherapy response of human breast cancers in which EMT is a critical component. Chemotherapy is a systemic treatment that destroys reproducing cells, but it cannot differentiate between normal and cancerous cells. Side effects occur when normal cells become damaged. Apart from the side effects of cancer chemotherapy, unexpected 'opposite effects' of chemotherapy, which enhance the critical steps in malignancy rather than inhibiting them, 1-3 have attracted progressively more attention, suggesting that novel strategies should be developed to reverse these opposite effects and render chemotherapy more effective.Tumor cells progress from non-invasive to malignant phenotypes via a series of critical steps that involve morphological changes referred to as the epithelial-mesenchymal transition (EMT). 4 EMT is a process originally observed during the embryonic development, in which cells lose epithelial characteristics. [5][6][7][8][9][10] With respect to the chemotherapy, recent studies have demonstrated a close link between EMT and insensitivity to chemotherapeutic agents. Hiscox et al. 11 showed increased b-catenin expression and elevated levels of transcription of b-catenin target genes known to be involved in tumor progression and EMT in the tamoxifen (TAM)-resistant MCF7 cells. Kajiyama et al. 12 identified an association between chronic paclitaxel resistance and induction of EMT in epithelial ovarian carcinomas. In addition, we previously showed that transient adriamycin treatmentinduced EMT and apoptosi...

We have established a national-wide BMD reference database at the LS and FN for Chinese adults and estimated the prevalence of osteoporosis in the middle-aged and elderly Chinese population.

This article presents a geometrically non-linear finite-element method for an accurate and efficient analysis of spatial cable structures. A two-node catenary cable element is formulated accurately considering the effect of self-weight of cable element. The tangent stiffness matrix of the cable element is derived as an accurate explicit expression of structural parameters and the nodal forces of the cable element are then also analytically calculated. Pre-stress in the cable element may be considered in the formulation. Three classical numerical examples are first provided to show the accuracy and efficiency of this method and the developed method is then applied to construction stage simulation in order to determine the erection parameters of a suspension bridge through progressive non-linear analysis. The cable element proposed can be conveniently used for the geometric non-linear analysis of flexible structures such as long-span suspension bridges, cable-stayed bridges, and tension structures.