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Antitumor effect of VEGFR2-targeted microbubble destruction with gemcitabine using an endoscopic ultrasound probe:In vivo mouse pancreatic ductal adenocarcinoma model

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Hepatobiliary & Pancreatic Diseases International 2020年第5期19卷 478-485页

作者： Nana Shimamoto Masaki ito Masafumi Chiba Sadamu Honma Hiroo Imazu Kazuki Sumiyama Department of Endoscopy The Jikei University School of Medicine3-25-8 Nishi ShinbashiMinato-kuTokyo 105-8461Japan Division of Oncology Research Center for Medical Science3-25-8 Nishi ShinbashiMinato-kuTokyo 105-8461Japan Division of Gastroenterology and Hepatology Department of MedicineNihon University School of Medicine30-1 Oyaguchikami-choItabashi-kuTokyo 173-8610Japan

Background:Ultrasound-targeted microbubble destruction(UTMD)induces cellular inflow of drugs at low intensity,while high intensity eradicates tumor *** vascular endothelial growth factor receptor 2(VEGFR2)is highly expressed in pancreatic ductal adenocarcinoma(PDAC),VEGFR2-targeted microbubble(MB)might additionally increase the tissue specificity of drugs and thus improve antitumor *** addition,fixing the dual pulse intensity could maximize MB *** study evaluated the one-off(experiment 1)and cumulative(experiment 2)treatment effect of UTMD by regulating the dual pulse output applied to PDAC using VEGFR2-targeted ***:C57BL/6 mice inoculated with Pan-02 cells were allocated to five groups:VEGFR2-targeted MB+gemcitabine(GEM),VEGFR2-targeted MB,non-targeted MB+GEM,GEM,and control *** injection of GEM or GEM and either VEGFR2-targeted or non-targeted MB,UTMD was applied for several minutes at low intensity followed by high intensity *** experiment 1,mice were treated by the protocol described above and then euthanized immediately or at the tumor diameter doubling time(TDT).In experiment 2,the same protocol was repeated weekly and mice were euthanized at TDT regardless of protocol *** analysis by CD31 and VEGFR2 staining provided microvascular density(MVD)and VEGFR2 expression along vessels(VEGFR2v)or intra/peripheral cells(VEGFR2c).Results:In experiment 1,TDT was significantly longer in the VEGFR2-targeted MB+GEM group compared to the non-targeted MB+GEM,GEM,and control groups,while the VEGFR2-targeted MB group showed no statistical *** and VEGFR2v in the immediate euthanasia was significantly lower in the VEGFR2-targeted MB+GEM and VEGFR2-targeted MB groups than other *** experiment 2,the VEGFR2-targeted MB+GEM group produced significantly longer TDT than the GEM or control groups,whereas the VEGFR2-targeted MB group showed no significant *** revealed sign

关键词： Ultrasound-targeted microbubble destruction VEGFR2-targeted microbubble Pancreatic ductal adenocarcinoma Gemcitabine

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Wind Tunnel Study on Wind and Turbulence Intensity Profiles in Wind Turbine Wake

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Journal of Thermal Science 2011年第2期20卷 127-132页

作者： Takao MAEDA Yasunari KAMADA Junsuke MURATA Sayaka YONEKURA Takafumi ito Atsushi OKAWA Tetsuya KOGAKI Division of Mechanical Engineering Mie University National Institute of Advanced Industrial Science and Technology

In recent years, there has been a rapid development of the wind farms in Japan. It becomes very important to investigate the wind turbine arrangement in wind farm, in order that the wake of one wind turbine does not to interfere with the flow in other wind turbines. In such a case, in order to achieve the highest possible efficiency from the wind, and to install as many as possible wind turbines within a limited area, it becomes a necessity to study the mutual interference of the wake developed by wind turbines. However, there is no report related to the effect of the turbulence intensity of the external flow on the wake behind a wind turbine generated in the wind tunnel. In this paper, the measurement results of the averaged wind profile and turbulence intensity profile in the wake in the wind tunnel are shown when the turbulence intensity of the external wind was changed. The wind tunnel experiment is performed with 500mm-diameter two-bladed horizontal axis wind turbine and the wind velocity in wake is measured by an I-type hot wire probe. As a result, it is clarified that high turbulence intensities enable to the entrainment of the main flow and the wake and to recover quickly the velocity in the wake.

关键词： Horizontal axis wind turbine Wake Wind profile Turbulence intensity Power output

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Microarray Analysis of the Developing Rat Mandible

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Acta Biochimica et Biophysica Sinica 2007年第6期39卷 399-405页

作者： Hideo KABURAGI Naoyuki SUGANO Maiko OSHIKAWA Ryosuke KOSHI Naoki SENDA Kazuhiro KAWAMOTO Koichi ito Department of Periodontology. Nihon University School of Dentistry Tokyo 101-8310 Japan Department of Periodontology. Nihon University School of Dentistry Tokyo 101-8310 Japan Division of Advanced Dental Treatment Dental Research Center Nihon University School of Dentistry Tokyo 101-8310 Japan Department of Periodontology. Nihon University School of Dentistry Tokyo 101-8310 JapanDivision of Advanced Dental Treatment Dental Research Center

To analyze the molecular events that occur in the developing mandible, we examined the expression of 8803 genes from samples taken at different time points during rat postnatal mandible development. Total RNA was extracted from the mandibles of 1-day-old, 1-week-old, and 2-week-old rats. Complementary RNA (cRNA) was synthesized from cDNA and biotinylated. Fragmented cRNA was hybridized to RGU34A GeneChip arrays. Among the 8803 genes tested, 4344 were detectable. We identified 148 genes with significantly increased expression, and 19 genes with significantly decreased expression. A comprehensive analysis appears to be an effective method of studying the complex process of development.

关键词： gene expression microarray rat mandible

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Measurement on Spot Size Dependence of Dense WDM Dielectric Multilayer Filters

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光学学报 2003年第S1期23卷 209-210页

作者： Masanobu ito Satoshi Suda Fumio Koyama Microsystem Research Center P&I Lab. Tokyo Institute of Technology 4259 Nagatsuta Midori-ku Yokohama 226-8503 JapanMicrosystem Research Center P&I Lab. Tokyo Institute of Technology 4259 Nagatsuta Midori-ku Yokohama 226-8503 JapanMicrosystem Research Center P&I Lab. Tokyo Institute of Technology 4259 Nagatsuta Midori-ku Yokohama 226-8503 Japan

We present the spot size dependence of dielectric multilayer filters for use in dense WDM systems. We found large dependences of filter performances on the spot size and the incident angle of input light, which should... 详细信息

关键词： DWDM in of Measurement on Spot Size Dependence of Dense WDM Dielectric Multilayer Filters for on

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MIXED MODES INTERLAMINAR FRACTURE TOUGHNESS OF CFRP LAMINATES TOUGHENED WITH CNF INTERLAYER

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Acta Mechanica Solida Sinica 2012年第3期25卷 321-330页

作者： Masahiro Arai Tatsuya Sasaki Satoshi Hirota Hiroaki ito Ning Hu Marino Quaresimin Shinshu University 4-17-1 Wakasato Nagano-shi Nagano 380-8553 Japan Chiba University 1-33 Yayoi-cho Inage-ku Chiba-shi Chiba 263-8522 Japan University of Padova Stradella San Nicola 3 36100 Vicenza Italy

In the present paper, the influence of carbon nanofiber on interlaminar fracture toughness of CFRP investigated using MMB（Mixed Mode Bending） tests. Vapor grown carbon fiber VGCF and VGCF-S, and multi-walled carbon nanotube MWNT-7 has been employed for the toughener of the interlayer on the CFRP laminates. In order to evaluate the fracture toughness and mixed mode ratio of it, double cantilever beam （DCB） tests, end notched fracture （ENF） tests and mixed mode bending （MMB） tests have been carried out. Boundary element analysis was applied to the CFRP model to compute the interlaminar fracture toughness, where extrapolation method was used to determine the fracture toughness and mixed mode ratio. The interlaminar fracture toughness and mixed mode ratio can be extrapolated by stress distribution in the vicinity of the crack tip of the CFRP laminate. It was found that the interlaminar fracture toughness of the CFRP laminates was improved inserting the interlayer made by carbon nanofiber especially in the region where shear mode deformation is dominant.

关键词： CFRP laminate fracture toughness interlaminar crack boundary element method,interlayer

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Diabetic neuropathy research: from mouse models to targets for treatment

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Neural Regeneration Research 2019年第11期14卷 1870-1879页

作者： Vuong M. Pham Shinji Matsumura Tayo Katano Nobuo Funatsu Seiji ito Department of Medical Chemistry Kansai Medical UniversityHirakataOsakaJapan Singapore Institute for Neurotechnology (SINAPSE) National University of SingaporeSingapore Department of Anesthesiology Osaka Medical CollegeTakatsukiOsakaJapan

Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.

关键词： brain derived neurotrophic factor diabetes extrinsic factors nerve growth factor nerve regeneration neurotrophic factors non-obese type 2 diabetes phosphatase and tensin homolog stem cell streptozotocin

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Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor

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World Journal of Gastroenterology 2008年第17期14卷 2740-2747页

作者： Yuji Ishii Ryota Saito Hideki Marushima Ryusuke ito Taro Sakamoto Katsuhiko Yanaga Department of Surgery the Jikei University School of Medicine

AIM： To examine the efficacy of the radial flow bioreactor （RFB） as an extracorporeal bioartificial liver （BAL） and the reconstruction of liver organoids using embryonic pig liver cells. METHODS： We reconstructed the liver organoids using embryonic porcine liver cells in the RFB. We also determined the gestational time window for the optimum growth of embryonic porcine liver cells. Five weeks of gestation was designated as embryonic day （E） 35 and 8 wk of gestation was designated as E56. These cells were cultured for one week before morphological and functional examinations. Moreover, the efficacy of pulsed adminisbation of a high concentration hepatocyte growth factor （HGF） was examined. RESULTS： Both cell growth and function were excellent after harvesting on E35. The pulsed administration of a high concentration of HGF promoted the differentiation and maturation of these fetal hepatic cells. Microscopic examination of organoids in the RFB revealed palisading and showed that bile duct-like structures were well developed, indicating that the organoids were mini livers. Transmission electron microscopy revealed microvilli on the luminal surfaces of bile duct-like structures and junctional complexes, which form the basis of the cytoskeleton of epithelial tissues. Furthermore, strong expression of connexin （Cx） 32, which is the main protein of hepatocyte gap junctions, was observed. With respect to liver function, ammonia detoxification and urea synthesis were shown to be performed effectively. CONCLUSION： Our system can potentially be applied in the fields of BAL and transplantation medicine.

关键词： Liver organoid Radial flow bioreactor Bioartificial liver Fetal porcine liver Hepatocyte growthfactor

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Lysophosphatidic acid induced nuclear translocation of nuclear factor-κB in Panc-1 cells by mobilizing cytosolic free calcium

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World Journal of Gastroenterology 2008年第28期14卷 4473-4479页

作者： Yoshiyuki Arita Tetsuhide ito Takamasa Oono Ken Kawabe Terumasa Hisano Ryoichi Takayanagi Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuoka 812-8582Japan

AIM: To clarify whether Lysophosphatidic acid (LPA) activates the nuclear translocation of nuclear factor-κB (NF-κB) in pancreatic cancer. METHODS: Panc-1, a human pancreatic cancer cell line, was used throughout the study. The expression of LPA receptors was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). Cytosolic free calcium was measured by fluorescent calcium indicator fura-2, and the localization of NF-κB was visualized by immunofluorescent method with or without various agents, which effect cell signaling. RESULTS: Panc-1 expressed LPA receptors, LPA1, LPA2 and LPA3. LPA caused the elevation of cytosolic free calcium dose-dependently. LPA also caused the nuclear translocation of NF-κB. Cytosolic free calcium was attenuated by pertussis toxin (PTX) and U73122, an inhibitor of phospholipase C. The translocation of NF-κB was similarly attenuated by PTX and U73122, but phorbol ester, an activator of protein kinase C, alone did not translocate NF-κB. Furthermore, the translocation of NF-κB was completely blocked by Ca2+ chelator BAPTA-AM. Thapsigargin, an endoplasmic- reticulum Ca2+-ATPase pump inhibitor, also promoted the translocation of NF-κB. Staurosporine, a proteinkinase C inhibitor, attenuated translocation of NF-κB induced by LPA. CONCLUSION: These findings suggest that protein kinase C is activated endogenously in Panc-1, and protein kinase C is essential for activating NF-κB with cytosolic calcium and that LPA induces the nuclear translocation of NF-κB in Panc-1 by mobilizing cytosolic free calcium.

关键词： Lysophosphatidic acid Nuclear translocation Nuclear factor-κB Cytosolic free calcium Panc-1

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Randomized controlled trial of pancreatic stenting to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

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World Journal of Gastroenterology 2012年第14期18卷 1635-1641页

作者： Yoshiaki Kawaguchi Masami Ogawa Fumio Omata Hiroyuki ito Tooru Shimosegawa Tetsuya Mine Division of Gastroenterology Tokai University School of MedicineIsehara 259-1193Japan Division of Gastroenterology Tohoku University Graduate School of Medicine1-1 Seiryo-machiAobakuSendai CityMiyagi 980-8574Japan

AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk ***:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and *** defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 *** were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent ***-ERCP pancreatitis was diagnosed according to consensus ***:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:*** the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:*** were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic *** frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),*** severity of pancreatitis was mild in all *** frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 *** rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-

关键词： Endoscopic retrograde cholangiopancreatography Pancreatitis Postoperative complications Prophylaxis Stents

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Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis

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World Journal of Gastroenterology 2006年第1期12卷 10-16页

作者： Masanori ito Shinji Tanaka Tomoari Kamada Ken Haruma Kazuaki Chayama Department of Medicine and Molecular Science Hiroshima UniversityHiroshimaJapan Department of Endoscopy Hiroshima University HospitalHiroshimaJapan Gastroenterology Unit Department of Internal MedicineKawasaki Medical SchoolKurashikiJapan

Many epidemiological reports indicate that Helicobacter pylori （H pylori） infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/ intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without precancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non- randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

关键词： H pylori Eradication Gastritis Gastric neoplasm, Endoscopy

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