Five bufadienolides (1-5) isolated from the leaves of Kalanchoe pinnata and K. daigremontiana x tubiflora (Crassulaceae) were examined for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. All bufadienolides showed inhibitory activity, and bryophyllin A (1) exhibited the most marked inhibition (IC50 = 0.4 microM) among the tested compounds. Bryophyllin C (2), a reduction analogue of 1, and bersaldegenin-3-acetate (3) lacking the orthoacetate moiety were less active. These results strongly suggest that bufadienolides are potential cancer chemopreventive agents.
In this contribution we show highly polarized photoluminescence (PL) from aligned polyethyleneoxide: polyphenylenevinylene derivative composite nanofibers. We demonstrate PL polarization ratios (parallel to perpendicular) greater than 13. This ratio is further increased (up to ∼25) by stretching the nanofibers. Stretching also results in an increase in conjugation length, fiber density, and PL lifetime. We argue that the effect of stretching is equivalent to applying a permanent and strong pressure. Our results open up the possibility for new optoelectronic devices and fundamental science studies based on polymer nanofibers.
Bone is the most frequent site of breast cancer metastasis, and once such metastasis occurs, complete remission is extremely difficult to achieve. In an effort to define the mechanisms underlying metastatic spread of breast cancer to bone, we previously developed and characterized the highly bone metastatic 4T1E/M3 mouse breast cancer cells. We found that following injection into mice, 4T1E/M3 cells exhibited greater bone metastasis and greater in vitro anchorage-independent growth and cell migration than their parental cells (4T1E). We also found that expression of intracellular adhesion molecule-1 (ICAM-1) is crucially involved in these metastatic activities of 4T1E/M3 cells. In the present study, our analysis of gene and protein expression revealed that production of chemokine CCL2 (MCP-1) is dramatically reduced in 4T1E/M3 cells, and that restoration of CCL2 expression in 4T1E/M3 cells diminishes their metastasis to bone and lung. Overexpression of CCL2 in 4T1E/M3 cells significantly reduced not only in vitro anchorage-independent cell growth and cell migration, but also mRNA and cell surface expression of ICAM-1. Conversely, knocking down CCL2 in 4T1E parental cells augmented their metastatic spread to spine and lung. The expression of ICAM-1 was also upregulated in 4T1E-derived CCL2 knockdown cells. Taken together, these results suggest that CCL2 expression may negatively regulate breast cancer metastasis to bone marrow and lung in our model and that expression of ICAM-1 plays a crucial role in that process.
Kinetically stabilized 1,2-dihydrodisilenes were successfully synthesized and isolated by the introduction of sterically protecting bulky aryl groups. These 1,2-dihydrodisilenes exhibit distinct Si═Si double-bond character in both solution and the solid state. The Si-H bonds in these 1,2-dihydrodisilenes exhibit higher s character than those of typical σ(4),λ(4)-hydrosilanes. Moderate heating of these 1,2-dihydrodisilenes in solution resulted in their isomerization to the corresponding trihydrodisilanes, with an intramolecular hydrogen migration as the rate-determining step.
As malignant breast cancers progress, they acquire the ability to spread to other regions of the body, including bone and lung, but the molecular mechanism underlying the increase in metastatic potential is not fully understood. Here we studied murine 4T1E/M3 highly bone marrow metastatic breast cancer cells, which we established previously. These cells show upregulated expression of bone morphogenetic protein (BMP) 7 and BMP receptors, as well as augmented phosphorylation of Smad1/5/8. Both anchorage-independent cell growth measured in colony forming assays and cell migration measured in wound healing assays were suppressed in 4T1E/M3 cells following treatment with a neutralizing anti-BMP7 antibody or knockdown of BMP7 gene expression. In addition, metastasis of 4T1E/M3 cells to the spine and lung and intracellular levels of phosphorylated Smad1/5/8 were suppressed by knocking down BMP7. Conversely, overexpression of BMP7 in the weakly metastatic parental 4T1E cells augmented their anchorage-independent growth, migration and metastasis to spine and lung. Taken together, our results strongly suggest that augmented autocrine BMP7 signaling leads to increases in the anchorage-independent cell growth, migration and metastatic potential in our bone marrow metastatic breast cancer model.
The effect of bait-delivered anthelmintic to reduce the prevalence of Echinococcus multilocularis in wild red foxes was evaluated in Koshimizu, in the eastern part of Hokkaido, Japan. The study area (200 km2) was divided into baited and non-baited sections. The anthelmintic baits were distributed around fox den sites in the baited section every month for 13 months. After 1 year of the anthelmintic bait distribution, the prevalence of E. multilocularis in foxes, evaluated either by the parasite egg examination (from 27.1 to 5.6%) or coproantigen ELISA (from 59.6 to 29.7%), decreased in the baited section contrasting to that in the non-baited section (parasite egg: from 18.8 to 24.2%; ELISA: from 41.9 to 45.8%). The prevalence of E. multilocularis in grey red-backed vole Clethrionomys rufocanus, caught around fox dens, born after bait distribution also decreased and was significantly lower than that in non-baited section. However, within the study periods, the coproantigen-positive rate in fox faeces sporadically increased, while egg-positive rate constantly decreased. Since coproantigen ELISA can detect pre-patent infection, this observation indicates that reinfection pressure in the baited section was still high even after the 13 months of anthelmintic bait distribution. Therefore, the bait distribution longer than our study period is required for the efficient control of E. multilocularis in wild red fox population.
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