Survivin is ubiquitously expressed in patients with head neck squamous cell carcinoma (HNSCC) and is associated with poor survival and chemotherapy resistance. Sepantronium bromide (YM155) is a selective survivin suppressant that exhibits potent antitumor activities by inducing apoptosis and autophagy in various types of cancer. However, the curative effects and underlying mechanisms of YM155 in HNSCC remain unclear. This study showed that survivin overexpression positively correlated with p-S6, p-Rb and LAMP2 but negatively correlated with the autophagic marker LC3 in human HNSCC tissues. In vitro studies revealed that YM155 triggered apoptosis of HNSCC cells in mitochondria and death receptor-dependent manner. The treatment also significantly enhanced autophagy by upregulating Beclin1, which led to cell death. YM155 not only downregulated the expression of survivin but also remarkably suppressed the activation of the mTOR signaling pathway in vitro and in vivo. YM155 displayed potent antitumor activities in both CAL27 xenograft and transgenic HNSCC mice models by delaying tumor onset and suppressing tumor growth. Furthermore, YM155 combined with docetaxel promoted tumor regression better than either treatment alone without causing considerable body weight loss in the HNSCC xenograft models. Overall, targeting survivin by YM155 can benefit HNSCC therapy by increasing apoptotic and autophagic cell death, and suppressing prosurvival pathways.
Dose effects of dietary isomalto-oligosacchrides (IMO) on broiler growth performance and characteristics of the intestinal microflora were compared. Three hundred sixty male broilers were randomly allotted to five treatments, with eight replicate pens per treatment and nine chicks per pen. Chicks were fed either a basal diet (control) or the basal diet plus 0.3, 0.6, 0.9, or 1.2% IMO. All chicks had access to feed and water ad libitum during the 7-wk experiment. At the end of the experiment, eight chicks per treatment were randomly chosen to measure the thymus index. Additionally, six birds per treatment were randomly selected to determine viable bacterial counts of Lactobacillus, Escherichia coli, and total aerobes in the digestive tract. The digesta of all the killed birds were also used to measure short-chain fatty acid (SCFA) levels. The results indicate that IMO enhanced growth performance during the initial 3 wk, but no further effects were detected during the latter 4 wk of the experiment. Isobutyrate level in crop content and acetate level in duodenum digesta were decreased by supplementation with IMO (P < 0.05). Isovalerate level in duodenum digesta was decreased in the 0.3 and 0.6% IMO groups (P < 0.001), whereas the jejunum butyrate and isobutyrate levels of the 0.3% IMO group were higher than in other groups (P < 0.05). The facultative microflora of the crop and cecum were not affected by IMO supplementation. However, the thymus index was increased significantly in chicks consuming diets containing 0.3% IMO.
These findings suggest SATB1 may play an important role in OSCC invasiveness and metastasis.
To minimize fluid leakage and improve rotordynamic stability of traditional seals, a new kind of radial annular seal is presented in this article. The structure and the sealing principle are analyzed. Compared to the traditional labyrinth seal, the fluid leakage direction is altered from the axial to radial direction. The flow resistance is increased, and the flowinduced force is reduced greatly. There is also a tremendous improvement in the wear resistance of the seal. Threedimensional numerical models of the traditional labyrinth seal and radial annular seal are set up. Calculated results show that the discharge coefficient of the radial annular seal is about 20% lower than that of the labyrinth seal. Though the rotating speed has a small influence on the radial seal force for both the radial annular seal and labyrinth seal, it has a large effect on the tangential seal force. The tangential seal force increases with the increasing speed, and the destabilizing force in the radial annular seal is reduced greatly when compared to that in the labyrinth seal. The radial seal force of the radial annular seal is about 1.5-2.5 times as strong as that of the labyrinth seal. The tangential seal force is about 30-50% lower than that of the labyrinth seal under the same eccentricity, and this ratio becomes larger and larger with the increasing speed. Finally, the dependency of the seal characteristics on the design parameters is studied. It is shown that the optimum ratios of the clearance s to the tooth thickness b (s/b) for the outward and inward flows are 4.5-5.5 and 11-13, respectively. The flow characteristics perform best with the ratio of the seal chamber width B to the tooth height H (B/H) on the same order of 5.5-7 for the two kinds of flows.
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