To study the role of periostin in adhesion formation, the effect of periostin antisense oligonucleotide (PAO) on adhesion formation was evaluated in mice. Under anesthesia, the serous membrane of the ...cecum was abraded, and the adhesion score and mRNA levels of periostin and its related factors were determined after surgery. Saline, 40 mg/kg of negative sense oligonucleotide (NSO), or 40 mg/kg of PAO were injected into the abdomen after surgery, and the adhesion score and mRNA levels were evaluated 14 days later. Filmy adhesion formation was observed 1 day after surgery, and the adhesion score increased gradually to 14 days. The mRNA levels of periostin, transforming growth factor (TGF)-β, and collagen I increased gradually from 3 days to 14 days. The adhesion score of PAO was significantly lower than of saline or NSO 14 days after surgery. The mRNA levels of periostin, TGF-β, and collagen I were also significantly attenuated by treatment with PAO compared with saline or NSO. Thus, these results demonstrated that the periostin mRNA level increased in the abraded cecum, and PAO prevented adhesion formation along with attenuation of the periostin mRNA level.
Metastasis is the leading cause of cancer death. A tumor‐supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in ...tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin‐induced lung fibrosis, and that up‐regulation of periostin expression coincided with activation of myofibroblasts positive for α‐smooth muscle actin. We established a lung metastasis model for B16 murine melanoma cells and showed that metastatic colonization of the lung by these cells was markedly promoted by bleomycin‐induced lung fibrosis. Inhibition of periostin expression by giving an intratracheal antisense oligonucleotide targeting periostin mRNA was found to suppress bleomycin‐induced lung fibrosis and thereby to attenuate metastatic colonization of the lung by melanoma cells. Our results indicate that periostin is a key player in the development of bleomycin‐induced fibrosis and consequent enhancement of tumor cell colonization in the lung. Our results therefore implicate periostin as a potential target for prevention or treatment of lung metastasis.
The authors provide new insights into the role of periostin in lung fibrosis and metastatic colonization. Inhibition of periostin implies a rational therapeutic concept for targeting the premetastatic niche which promotes lung metastasis.
Retinal neovascularization (NV) due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin ...(POSTN) may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs) in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.
We report herein an extremely rare complication; namely, endo‐clip migration into the common bile duct, following laparoscopic cholecystectomy, that occurred in a 57‐year‐old man. He underwent ...laparoscopic cholecystectomy, but postoperative bile leakage occurred from the cystic duct stump and he was treated by conservative drainage for 1 month. Five years later, he complained of vomiting and pain in the right hypochondrium, and he was admitted for investigations of jaundice and liver dysfunction. Computerized tomography scanning of the abdomen and endoscopic retrograde cholangiography revealed that several calculi, with six endo‐clips as nuclei, had migrated into the biliary tract. Endoscopic removal of the calculi following endoscopic sphincterotomy, using a basket catheter, was unsuccessful, and it was therefore necessary to remove the basket catheter surgically. The mechanism of endo‐clip migration and the method for removing the endo‐clips are briefly discussed.
We investigated that the structural changes in the depth direction of the bottom layer for multi layer process and the effects on improving the resistance against the dry etching process by H2 plasma ...curing. Diamond like amorphous carbon structure that included sp2 and sp3 carbon cluster was generated near the surface by H2 plasma treatment. The diamond like amorphous carbon was harder than polymer material and had good resistance to the dry etching process in generally. It was cleared that the thickness of the modified layer was approximately 50nm by means of a spectroscopic ellipsometry. Although the thickness of the modified layer was decreased by the dry etching process, the entire region of the modified layer did not disappear after the dry etching process. Therefore, the resistance of the modified layer against the dry etching process maintained and it was confirmed that the modification (hardening process) by H2 plasma treatment had the effect on improving the resistance of the sample against the dry etching process. In addition, it could be expected that H2 plasma treatment had this effect in plural sample structure.
Suppression of 193-nm photoresist deformation by H
2 addition to fluorocarbon plasmas in via-hole etching is investigated for sub-65-nm-node dual-damascene patterning. Photoresist deformation causes ...profile distortion and results in degradation of reliability, such as the line-to-line time dependent dielectric breakdown. To prevent profile distortion, H
2 addition to fluorocarbon plasma is investigated in terms of fluorocarbon polymer and photoresist modification. XPS, FT-IR, and highlight etching investigations reveal that the H
2 plasma treatment extracts oxygen from the photoresist and modifies it. This modification suppresses the photoresist deformation and H
2 addition to fluorocarbon plasmas can have the same effects as the H
2 plasma treatment. Finally, a highly reliable damascene interconnection is successfully achieved.
Surface roughness of strain-relaxed Si sub(1-x)Ge sub(x) layers grown on Si(100) surfaces by a two-step growth method has been investigated. It has been found that the roughness is much smaller than ...that of layers grown by a conventional one-step growth method. The roughness depends on the Ge fraction and is increased at higher Ge fractions. In solid-phase epitaxial (SPE) of the first layer at a high Ge fraction of x identical with 0.8, an increase in thickness brings about a marked decrease in the roughness of the first layer. On the other hand, at x identical with 0.3, the roughness increases as increasing the thickness, which is considered to be due to atomic rearrangement in SPE.
The rate of dephosphorylation of isolated P-H2B histone by pig heart phosphoprotein phosphatase (Mr = 224,000) and its catalytic subunit (Mr = 31,000) was suppressed more than 95 % at low ionic ...strength when the substrate was integrated into nucleosome core particles. The suppressed rate was increased 13–43-fold by polyamine hydrochlorides and Mg(CH3COO)2 at the optimal ionic strength of 0.2–0.38 M. Phosphatase activity toward integrated P-H2B histone was distributed in both rat liver cytosol and nuclear extracts. The phosphatase activities in these fractions showed similar specific activities and were also increased 10–32-fold by 10 mM spermine 4HCl.
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