To clarify the influence of surface steps on the diffusion of adsorbed oxygen atoms on Pt, we have carried out density functional calculations of the adsorption of atomic oxygen on a Pt(211) stepped surface and the diffusion barriers between the adsorbed states. Comparison with Pt(111) and Pt(100) flat surfaces reveals that atomic oxygen is strongly bound at the ledge of the steps and weakly bound at the bottom of the steps. We show that the variation in the adsorption preferences correlates well with the d-band centers of the outermost Pt atoms on a clean Pt(211) surface. Although a high-energy barrier of E diff,⊥ = 1.36 eV is obtained for diffusion perpendicular to the step edge, the barrier lies within the range of experimental values. The energy barrier also depends on whether the O atom is ascending or descending the step, being about 0.3 eV lower in the case of the former. The barrier to diffusion parallel to the edge of E diff,|| = 0.73 eV is also higher compared with the equivalent barrier on a flat Pt(111) surface due to the deeper energy well at the ledge.
Pancreatic cancer is highly malignant, characterized by aggressive proliferation, invasion, and metastasis. α-Bisabolol is an oily sesquiterpene alcohol derived from a variety of plants. We previously demonstrated that α-bisabolol is a potential therapeutic agent for pancreatic cancer. The aim of this study was to develop α-bisabolol derivatives which are more potent than the parent compound and may be clinically useful against pancreatic cancer. First, 22 derivatives of α-bisabolol were designed and synthesized. α-Bisabolol derivatives and had more potent inhibitory effects on the proliferation of pancreatic cancer cells than did α-bisabolol. Next, 15 additional α-bisabolol derivatives were designed and synthesized based on the structure of α-bisabolol derivatives and Among them, α-bisabolol derivative had the strongest inhibitory effect on proliferation. This novel compound reduced the proliferation of various pancreatic cancer cell lines, such as KLM1, Panc1, and KP4. In addition, the compound induced higher levels of apoptosis in pancreatic cancer cell lines than did α-bisabolol. α-Bisabolol derivative inhibited xenograft tumor growth and reduced dissemination of pancreatic cancer to peritoneal nodules. The compound strongly suppressed AKT expression in the peritoneal nodules. Reduced AKT expression in peritoneal nodules is consistent with an anticancer effect. These data indicate that α-bisabolol derivative effectively prevents the progression of pancreatic cancer via inhibition of AKT. Taken together, the results showed that this compound has attractive therapeutic properties as a novel anticancer drug for pancreatic cancer.
The targeting protein for Xklp2 (TPX2) is a microtubule- and, cell cycle-associated protein who’s overexpression has been reported in various malignancies. In this study, we verified the overexpression of TPX2 in both surgically resected specimens of pancreatic cancer and multiple pancreatic cancer cell lines. Subsequently, we found that TPX2 siRNA effectively suppressed the proliferation of pancreatic cancer cells in culture, and the direct injection of TPX2 siRNA into subcutaneously implanted pancreatic cancer cells in nude mice revealed antiproliferative effects. These results implied a therapeutic potential of TPX2 siRNA in pancreatic cancer. Among 56 angiogenesis-related factors examined using angiogenesis arrays, the average protein levels of insulin-like growth factor-binding protein-3 (IGFBP-3) were significantly higher in TPX2 siRNA-treated tumors than in the Control siRNA-treated tumors. Moreover, we demonstrated that CD34-positive microvessels were significantly reduced in tumors treated with TPX2 siRNA compared to tumors that treated with Control siRNA. The attenuated expression of CD34 in TPX2 siRNA-treated tumors coincided with the overexpression of IGFBP-3. These results indicated that TPX2 has an impact on tumor angiogenesis in pancreatic cancer. The results also implied that the antiangiogenic effect observed in TPX2 siRNA-treated pancreatic cancer cells may be partly explained by the upregulation of IGFBP-3.
Phytohemagglutinin-induced lymphocyte transformation (PHA-T) was depressed in pregnant women, as compared with that in nonpregnant women. Pregnancy serum had a suppressive action on PHA-T which was enhanced with the advance in pregnancy. Hydrocortisone, progesterone, Α-fetoprotein, and trophoblast-specific antigen, were demonstrated as immune suppressive factors. From these results, it was concluded that cell-mediated immunity might be reduced in pregnant women and that this reduction might be one of the causes for the maintenance of pregnancy.
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